IP Library › Granted Patent US 12,281,097
Granted Patent B2
US 12,281,097 · App. 17/990,133 · Granted Apr 22, 2025

Isoquinolin-3-yl carboxamides and preparation and use thereof

Inventors: Sunil Kumar KC (San Diego, CA); Chi Ching Mak (San Diego, CA); Brian Walter Eastman (San Diego, CA); Jianguo Cao (San Diego, CA); Venkataiah Bollu (San Diego, CA); Gopi Kumar Mittapalli (San Diego, CA); Chandramouli Chiruta (San Diego, CA)
Assignee: BioSplice Therapeutics, Inc.
C07D401/14C07D401/04C07D405/14C07D409/14C07D413/14C07D417/04C07D417/14C07D471/08C07D471/10C07D487/04C07D487/08C07D491/048
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Quick Facts
Patent No.
US 12,281,097
App. No.
17/990,133
Granted
Apr 22, 2025
Kind
B2
Abstract

Isoquinoline compounds for treating various diseases and pathologies are disclosed. More particularly, the present invention concerns the use of an isoquinoline compound or analogs thereof, in the treatment of disorders characterized by the activation of Wnt pathway signaling (e.g., cancer, abnormal cellular proliferation, angiogenesis, fibrotic disorders, bone or cartilage diseases, and osteoarthritis), the modulation of cellular events mediated by Wnt pathway signaling, as well as genetic diseases and neurological conditions/disorders/diseases due to mutations or dysregulation of the Wnt pathway and/or of one or more of Wnt signaling components. Also provided are methods for treating Wnt-related disease states.

Claims (24)

1. A pharmaceutical composition comprising a compound which is

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

2. A method of treating cancer in a mammal, wherein the cancer is selected from: breast cancers, colorectal cancers, tumors of the hematopoietic and lymphoid tissues, liver cancers, lung cancers, ovarian cancers, pancreatic cancers, and prostate cancers, the method comprising administering to the patient a therapeutically effective amount of a compound, having the structure of:

or a pharmaceutically acceptable salt thereof.

3. A method of treating cancer in a mammal, wherein the cancer is selected from: breast cancers, colorectal cancers, tumors of the hematopoietic and lymphoid tissues, liver cancers, lung cancers, ovarian cancers, pancreatic cancers, and prostate cancers, the method comprising administering to the patient a therapeutically effective amount of a pharmaceutical composition comprising a compound having the structure of:

or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

4. The method of claim 3 , wherein the cancer is a breast cancer.

5. The method of claim 3 , wherein the cancer is a colorectal cancer.

6. The method of claim 3 , wherein the cancer is a tumor of the hematopoietic and lymphoid tissues.

7. The method of claim 3 , wherein the cancer is a liver cancer.

8. The method of claim 3 , wherein the cancer is a lung cancer.

9. The method of claim 3 , wherein the cancer is an ovarian cancer.

10. The method of claim 3 , wherein the cancer is a pancreatic cancer.

11. The method of claim 3 , wherein the cancer is a prostate cancer.

12. The method of claim 3 , wherein the mammal is a human.

13. The method of claim 2 , wherein the cancer is a breast cancer.

14. The method of claim 2 , wherein the cancer is a colorectal cancer.

15. The method of claim 2 , wherein the cancer is a tumor of the hematopoietic and lymphoid tissues.

16. The method of claim 2 , wherein the cancer is a liver cancer.

17. The method of claim 2 , wherein the cancer is a lung cancer.

18. The method of claim 2 , wherein the cancer is an ovarian cancer.

19. The method of claim 2 , wherein the cancer is a pancreatic cancer.

20. The method of claim 2 , wherein the cancer is a prostate cancer.

21. The method of claim 2 , wherein the mammal is a human.

Assignments (5)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 27, 2026
From: BIOSPLICE THERAPEUTICS, INC.
To: TENARX, INC.
Reel/Frame 074209/0693 →
RELEASE OF SECURITY INTEREST Recorded Mar 12, 2026
From: TMF GROUP NEW YORK, LLC, NOT INDIVIDUALLY BUT SOLELY AS COLLATERAL AGENT
To: BIOSPLICE THERAPEUTICS, INC.
Reel/Frame 075109/0434 →
SECURITY INTEREST Recorded May 10, 2024
From: BIOSPLICE THERAPEUTICS, INC.
To: VICKERS VENTURE FUND VI PTE. LTD.; VICKERS VENTURE FUND VI (PLAN) PTE. LTD.; VICKERS-SPLICE CO-INVESTMENT LLC; MED-PATHWAYS II LIMITED
Reel/Frame 067382/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: KUMAR KC, SUNIL; MAK, CHI CHING; EASTMAN, BRIAN WALTER; CAO, JIANGUO; BOLLU, VENKATAIAH; MITTAPALLI, GOPI KUMAR; CHIRUTA, CHANDRAMOULI
To: SAMUMED, LLC
Reel/Frame 063227/0696 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 5, 2023
From: SAMUMED, LLC
To: BIOSPLICE THERAPEUTICS, INC.
Reel/Frame 063255/0849 →
Continuity (6)
Continuation 17155577 · Jan 22, 2021
Continuation 16703321 · Dec 4, 2019
Continuation 16130842 · Sep 13, 2018
Continuation 15499013 · Apr 27, 2017
Provisional Application 62328255 · Apr 27, 2016
Related Publication 20230286945A1 · Sep 14, 2023
References Cited (354)
US 4164559A · Miyata et al. · 1979 [cited by applicant]
US 4474752A · Haslam et al. · 1984 [cited by applicant]
US 6093730A · Weidmann et al. · 2000 [cited by applicant]
US 6120484A · Silverstein · 2000 [cited by applicant]
US 6172058B1 · Tercero et al. · 2001 [cited by applicant]
US 6377849B1 · Lenarz et al. · 2002 [cited by applicant]
US 6440102B1 · Arenberg et al. · 2002 [cited by applicant]
US 6648873B2 · Arenberg et al. · 2003 [cited by applicant]
US 6911211B2 · Eini et al. · 2005 [cited by applicant]
US 7998878B2 · Levy et al. · 2011 [cited by applicant]
US 7998978B2 · Huang et al. · 2011 [cited by applicant]
US 8088793B2 · Qian et al. · 2012 [cited by applicant]
US 8119655B2 · Dong et al. · 2012 [cited by applicant]
US 8697887B2 · Hood et al. · 2014 [cited by applicant]
US 9090613B2 · Hood et al. · 2015 [cited by applicant]
US 9221793B2 · Hood et al. · 2015 [cited by applicant]
US 9346812B2 · Calabrese et al. · 2016 [cited by applicant]
US 9428509B2 · Calabrese et al. · 2016 [cited by applicant]
US 9475807B2 · Kc et al. · 2016 [cited by applicant]
US 9475825B2 · Kc et al. · 2016 [cited by applicant]
US 9493487B2 · Kc et al. · 2016 [cited by applicant]
US 9540398B2 · Kc et al. · 2017 [cited by applicant]
US 9546185B2 · Kc et al. · 2017 [cited by applicant]
US 9557993B2 · Sanghai et al. · 2017 [cited by applicant]
US 9657016B2 · Kc et al. · 2017 [cited by applicant]
US 9738638B2 · Kc et al. · 2017 [cited by applicant]
US 9745271B2 · Hood et al. · 2017 [cited by applicant]
US 9758531B2 · Kc et al. · 2017 [cited by applicant]
US 9908867B2 · Kc et al. · 2018 [cited by applicant]
US 9951048B1 · Kc et al. · 2018 [cited by applicant]
US 10100038B2 · Kc et al. · 2018 [cited by applicant]
US 10106527B2 · Kc et al. · 2018 [cited by applicant]
US 10287267B2 · Kc et al. · 2019 [cited by applicant]
US 10508099B2 · Kc et al. · 2019 [cited by applicant]
US 10544128B2 · Kc · 2020 [cited by examiner]
US 10556885B2 · Kc et al. · 2020 [cited by applicant]
US 10947217B2 · Kc et al. · 2021 [cited by applicant]
US 11174244B2 · Kc et al. · 2021 [cited by applicant]
US 11548872B2 · Kc et al. · 2023 [cited by applicant]
US 11673881B2 · Kc et al. · 2023 [cited by applicant]
US 20060264897A1 · Lobl · 2006 [cited by applicant]
US 20070142428A1 · Seiler · 2007 [cited by applicant]
US 20070248590A1 · Milne et al. · 2007 [cited by applicant]
US 20110190290A1 · Hood et al. · 2011 [cited by applicant]
US 20120035194A1 · Huang et al. · 2012 [cited by applicant]
US 20130096119A1 · Bur et al. · 2013 [cited by applicant]
US 20140088076A1 · Lyssikatos et al. · 2014 [cited by applicant]
US 20150045379A1 · Hood et al. · 2015 [cited by applicant]
US 20170313681A1 · Kc et al. · 2017 [cited by applicant]
US 20170313682A1 · Kc et al. · 2017 [cited by applicant]
US 20180155323A1 · Kc et al. · 2018 [cited by applicant]
US 20180208580A1 · Kc et al. · 2018 [cited by applicant]
US 20180222887A1 · Kc et al. · 2018 [cited by applicant]
US 20200299263A1 · Kc et al. · 2020 [cited by applicant]
US 20200339536A1 · Kc et al. · 2020 [cited by applicant]
US 20220062240A1 · Tam et al. · 2022 [cited by applicant]
US 20220332698A1 · Kc et al. · 2022 [cited by applicant]
US 20230104155A1 · Kc et al. · 2023 [cited by applicant]
CL 200802411 · 2009 [cited by applicant]
CN 1218802 · 1999 [cited by applicant]
CN 1394205 · 2003 [cited by applicant]
CN 1671710 · 2005 [cited by applicant]
CN 1784404 · 2006 [cited by applicant]
CN 1829713 · 2006 [cited by applicant]
CN 101440092 · 2009 [cited by applicant]
CN 101821279 · 2010 [cited by applicant]
CN 102558173 · 2012 [cited by applicant]
CN 102844305 · 2012 [cited by applicant]
CN 103261167 · 2013 [cited by applicant]
CN 103929963 · 2014 [cited by applicant]
CN 105037355 · 2015 [cited by applicant]
EA 021225 · 2015 [cited by applicant]
EP 3448838 · 2019 [cited by applicant]
EP 3448386 · 2021 [cited by applicant]
JP H11302257 · 1999 [cited by applicant]
JP 2006525976 · 2006 [cited by applicant]
JP 2009535393 · 2009 [cited by applicant]
JP 2010536752 · 2010 [cited by applicant]
JP 2013501792 · 2013 [cited by applicant]
JP 2013523715 · 2013 [cited by applicant]
JP 2014502601 · 2014 [cited by applicant]
JP 2014526510 · 2014 [cited by applicant]
KZ 20122 · 2017 [cited by applicant]
RU 2331640 · 2008 [cited by applicant]
WO WO1987005297 · 1987 [cited by applicant]
WO WO1996002537 · 1996 [cited by applicant]
WO WO2001002369 · 2001 [cited by applicant]
WO WO2001053268 · 2001 [cited by applicant]
WO WO2001083481 · 2001 [cited by applicant]
WO WO2003004488 · 2003 [cited by applicant]
WO WO2003035005 · 2003 [cited by applicant]
WO WO2003035065 · 2003 [cited by applicant]
WO WO2003035644 · 2003 [cited by applicant]
WO WO2003051366 · 2003 [cited by applicant]
WO WO2003070236 · 2003 [cited by applicant]
WO WO2003070706 · 2003 [cited by applicant]
WO WO2003097610 · 2003 [cited by applicant]
WO WO2003101968 · 2003 [cited by applicant]
WO WO2003101993 · 2003 [cited by applicant]
WO WO2004014864 · 2004 [cited by applicant]
WO WO2004031158 · 2004 [cited by applicant]
WO WO2004076450 · 2004 [cited by applicant]
WO WO2005009997 · 2005 [cited by applicant]
WO WO2005012256 · 2005 [cited by applicant]
WO WO2005014554 · 2005 [cited by applicant]
WO WO2005047266 · 2005 [cited by applicant]
WO WO2005049019 · 2005 [cited by applicant]
WO WO2005092890 · 2005 [cited by applicant]
WO WO2005099703 · 2005 [cited by applicant]
WO WO2005110410 · 2005 [cited by applicant]
WO WO2006001894 · 2006 [cited by applicant]
WO WO2006015124 · 2006 [cited by applicant]
WO WO2006024945 · 2006 [cited by applicant]
WO WO2006054143 · 2006 [cited by applicant]
WO WO2006054151 · 2006 [cited by applicant]
WO WO2006063302 · 2006 [cited by applicant]
WO WO2006063841 · 2006 [cited by applicant]
WO WO2006130673 · 2006 [cited by applicant]
WO WO2007061360 · 2007 [cited by applicant]
WO WO2007107346 · 2007 [cited by applicant]
WO WO2007117465 · 2007 [cited by applicant]
WO WO2007125405 · 2007 [cited by applicant]
WO WO2008061109 · 2008 [cited by applicant]
WO WO2008071397 · 2008 [cited by applicant]
WO WO2008071398 · 2008 [cited by applicant]
WO WO2008071451 · 2008 [cited by applicant]
WO WO2008124848 · 2008 [cited by applicant]
WO WO2008137408 · 2008 [cited by applicant]
WO WO2008140792 · 2008 [cited by applicant]
WO WO2008147713 · 2008 [cited by applicant]
WO WO2008150914 · 2008 [cited by applicant]
WO WO2008154241 · 2008 [cited by applicant]
WO WO2008156757 · 2008 [cited by applicant]
WO WO2009011850 · 2009 [cited by applicant]
WO WO2009016072 · 2009 [cited by applicant]
WO WO2009061345 · 2009 [cited by applicant]
WO WO2009085226 · 2009 [cited by applicant]
WO WO2010064875 · 2010 [cited by applicant]
WO WO2010107765 · 2010 [cited by applicant]
WO WO2010111060 · 2010 [cited by applicant]
WO WO2011011722 · 2011 [cited by applicant]
WO WO2011019648 · 2011 [cited by applicant]
WO WO2011019651 · 2011 [cited by applicant]
WO WO2011050245 · 2011 [cited by applicant]
WO WO2011079076 · 2011 [cited by applicant]
WO WO2011084486 · 2011 [cited by applicant]
WO WO2011121555 · 2011 [cited by applicant]
WO WO2011123890 · 2011 [cited by applicant]
WO WO2012068589 · 2012 [cited by applicant]
WO WO2012080284 · 2012 [cited by applicant]
WO WO2012104388 · 2012 [cited by applicant]
WO WO2012129562 · 2012 [cited by applicant]
WO WO2013024011 · 2013 [cited by applicant]
WO WO2013040215 · 2013 [cited by applicant]
WO WO2013169793 · 2013 [cited by applicant]
WO WO2015143380 · 2015 [cited by applicant]
WO WO2016046530 · 2016 [cited by applicant]
WO WO2017189823 · 2017 [cited by applicant]
WO WO2017189829 · 2017 [cited by applicant]
WO WO2018064545 · 2018 [cited by applicant]
WO WO2020150545 · 2020 [cited by applicant]
U.S. Appl. No. 15/884,112, filed Jan. 30, 2018, Kumar KC et al. [cited by applicant]
Bharath Rao et al, “Evaluation of Myofibroblasts by Expression of Alpha Smooth Muscle Actin: A Marker in Fibrosis, Dysplasia and Carcinoma,” Journal of Clinical and Diagnostic Research, Apr. 2014, 4(4):ZC14-ZC17. [cited by applicant]
Bollong et al., “Small molecule-mediated inhibition of myofibroblast transdifferentiation for the treatment of fibrosis,” PNAS, May 2017, 114(18):4679-4684. [cited by applicant]
Carpino et al., “Alpha-SMA expression in hepatic stellate cells and quantitative analysis of hepatic fibrosis in cirrhosis and in recurrent chronic hepatitis after liver transplantation,” Digestive and Liver Disease, Ma… [cited by applicant]
Chou et al., “Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors,” Advances in enzyme regulation, Jan. 1, 1984, 22:27-55. [cited by applicant]
Cisternas et al., “Role of Wnt Signaling in Tissue Fibrosis, Lessons from Skeletal Muscle and Kidney,” Current Molecular Medicine, 2014, 14(4):510-522. [cited by applicant]
Clevers et al., “Wnt/β-catenin signaling and disease,” [cited by applicant]
clinicaltrials.gov [online] “A Long-Term Safety and Efficacy Study of Lorecivivint in Subjects With Osteoarthritis of the Knee” dated Aug. 20, 2020, retrieved on Aug. 17, 2022, retrieved from URL<https://clinicaltrials.… [cited by applicant]
Datta et al., “Novel therapeutic approaches for pulmonary fibrosis,” [cited by applicant]
Deshmukh et al., “A small-molecule inhibitor of the Wnt pathway, lorecivivint (SM04690), as a potential disease-modifying agent for the treatment of degenerative disc disease,” The Spine Journal, Sep. 1, 2020, 20(9):149… [cited by applicant]
Extended European Search Report in European Appln. No. 21159576.4, dated Aug. 16, 2021, 8 pages. [cited by applicant]
Extended European Search Report in European Appln. No. 21181038.7, dated Dec. 3, 2021, 11 pages. [cited by applicant]
Guo et al., “Wnt/β-Catenin Signaling: a Promising New Target for Fibrosis Diseases,” Physiol. Res., 2012, 61:337-346. [cited by applicant]
He et al., “Synthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) Inhibitors,” Bioorganic & Medicinal Chemistry Letters, 2011, 21(6), 1719-1723. [cited by applicant]
Hiyama et al., “A complex interaction between Wnt signaling and TNF-α in nucleus pulposus cells,” Arthritis research & therapy, Dec. 2013, 15(6):1-11. [cited by applicant]
Ionescu et al., “DYRK1A kinase inhibitors with emphasis on cancer,” Mid-Reviews in Medicinal Chemistry, Nov. 2012, 12(13):1315-1329. [cited by applicant]
Iwai et al., “Anti-tumor efficacy of a novel CLK inhibitor via targeting RNA splicing and MYC-dependent vulnerability,” EMBO molecular medicine, Jun. 2018, 10(6):e8289, 15 pages. [cited by applicant]
Kim et al., “Blockade of the Wnt/B-Catenin Pathway Attenuates Bleomycin-Induced Pulmonary Fibrosis,” Tohoku J. Exp. Med., 2011, 223:45-54. [cited by applicant]
King et al., “BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis,” [cited by applicant]
Leyns et al., “Frzb-1 Is a Secreted Antagonist of Wnt Signaling Expressed in the Spemann Organizer,” Cell, Mar. 21, 1997, 88(6):747-756. [cited by applicant]
Lin et al., “The Effects and Possible Mechanisms of Puerarin to Treat Uterine Fibrosis Induced by Ischemia-Reperfusion Injury in Rats,” Medical Science monitor, 2017, 23:3404-3411. [cited by applicant]
Liu, et.al., “Fibrotic lung fibroblasts show blunted inhibition by cAMP due to deficient cAMP response element-binding protein phosphorylation,” [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/884,112, dated Mar. 8, 2018, 7 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/498,990, dated Jun. 14, 2018, 13 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/499,013, dated Jan. 26, 2018, 10 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/925,157, dated Aug. 8, 2018, 11 pages. [cited by applicant]
Non-Final Office Action for U.S. Appl. No. 15/943,864, dated Aug. 9, 2018, 11 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Application No. PCT/US2017/029797, dated Dec. 29, 2017, 10 pages. [cited by applicant]
PCT International Search Report and Written Opinion in International Application No. PCT/US2017/29805, dated Jul. 31, 2017, 9 pages. [cited by applicant]
PCT Invitation to Pay Additional Fees in International Application No. PCT/US2017/029797, dated Jun. 26, 2017, 2 pages. [cited by applicant]
PUBCHEM. Substance Record for SID 162584226. Deposit Date: May 22, 2013. [retrieved on Jun. 13, 2017]. Retrieved from the Internet. <URL: https://pubchem.ncbi.nlm.nih.gov/substance/162584226#sectio>, 5 pages. [cited by applicant]
RU Office Action in Russian Appln. No. 2018141379, dated Aug. 13, 2020, 20 pages (with English translation). [cited by applicant]
Staines et al., “Cartilage development and degeneration: a Wnt Wnt situation,” Cell biochemistry and function, Dec. 2012, 30(8):633-642. [cited by applicant]
Stotani et al., “DYRK1A inhibition as potential treatment for Alzheimer's disease,” Future Medicinal Chemistry, Apr. 2016, 8(6):681-696. [cited by applicant]
Supplementary European Search Report in European Appln. No. 19824758.7, dated Jun. 24, 2022, 13 pages. [cited by applicant]
Surendran, “Wnt-Dependent B-Catenin Signaling Is Activated after Unilateral Ureteral Obstruction, and Recombinant Secreted Frizzled-Related Protein 4 Alters the Progression of Renal Fibrosis,” J. Am. Soc. Nephrol., 2005… [cited by applicant]
Watts et.al., “RhoA signaling modulates cyclin D1 expression in human lung fibroblasts; implications for idiopathic pulmonary fibrosis,” [cited by applicant]
Wei et al., “Canonical Wnt Signaling Induces Skin Fibrosis and Subcutaneous Lipoatrophy,” Arthritis & Rheumatism, Jun. 2011, 63(6):1707-1717. [cited by applicant]
Wu et al., “Design and synthesis of novel substituted naphthyridines as potential c-Met kinase inhibitors based on MK-2461,” Bioorganic & medicinal chemistry letters. Aug. 15, 2015, 25(16):3251-3255. [cited by applicant]
Wynn et al., “Mechanisms of fibrosis: therapeutic translation for fibrotic disease,” Nature Medicine, Jul. 2012, 18(7):1028-1040. [cited by applicant]
Yazici et al., “A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis,” Osteoarthritis and cartilage, May 1, 2021, 29(5):654-666. [cited by applicant]
Zhang et al., “Research progress of dual specificity tyrosine-phosphorylation-regulated kinase 1A,” Xiandai Zhongliu Yixue (2015), 23(15):2223-2226 (abstract only). [cited by applicant]
Loeser et al., “Mitogen-activated protein kinases as therapeutic targets in osteoarthritis,” Current Opinion in Rheumatology, Sep. 1, 2008, 20(5):581-586. [cited by applicant]
Adaimy et al., “Mutation in WNT10A Is Associated with an Autosomal Recessive Ectodermal Dysplasia: The Odonto-onycho-dermal Dysplasia,” The American Journal of Human Genetics, Oct. 1, 2007, 81(4):821-828. [cited by applicant]
Anastas et al., “WNT signalling pathways as therapeutic targets in cancer,” Nature Reviews Cancer, Jan. 2013, 13(1):11-26. [cited by applicant]
Andres, “Molecular genetics and animal models in autistic disorder,” Brain Research Bulletin, Jan. 1, 2002, 57(1):109-119. [cited by applicant]
Anko, “Regulation of gene expression programmes by serine-arginine rich splicing factors,” Seminars in Cell & Developmental Biology, Academic Press, Aug. 1, 2014, 32:11-21. [cited by applicant]
Araki et al., “Inhibitors of CLK protein kinases suppress cell growth and induce apoptosis by modulating pre-mRNA splicing,” PloS One, Jan. 12, 2015, 10(1):e0116929. [cited by applicant]
Arce et al., “Diversity of LEF/TCF action in development and disease,” Oncogene, Dec. 2006, 25(57):7492-7504. [cited by applicant]
Barker et al., “Mining the Wnt pathway for cancer therapeutics,” Nature Reviews Drug Discovery, Dec. 1, 2006, 5(12):997-1014. [cited by applicant]
Beyer et al., “Extended report: β-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis,” Annals of the Rheumatic Diseases, May 1, 2012, 71(5):761-767. [cited by applicant]
Biason-Lauber et al., “A WNT4 Mutation Associated with Müllerian-Duct Regression and Virilization in a 46, XX Woman,” N. Engl. J. Med., Aug. 2004, 351(8):792-798. [cited by applicant]
Blaydon et al., “The gene encoding R-spondin 4 (RSPO4), a secreted protein implicated in Wnt signaling, is mutated in inherited anonychia,” Nat. Genet., Nov. 2006, 38(11):1245-1247. [cited by applicant]
Blom et al., “Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1,” Arthritis Rheum., Feb. 2009, 60(2):501-512. [cited by applicant]
Boyden et al., “High Bone Density Due to a Mutation in LDL-Receptor-Related Protein 5,” N. Engl. J. Med., May 2002, 346(20):1513-1521. [cited by applicant]
Brack et al., “Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis,” Science, Aug. 2007, 317(5839):807-810. [cited by applicant]
Brown et al., “Toxicity and toxicokinetics of the cyclin-dependent kinase inhibitor AG-024322 in cynomolgus monkeys following intravenous infusion,” Cancer Chemother Pharmacol., May 2008, 62(6):1091-1101. [cited by applicant]
Chilosi et al., “The pathogenesis of COPD and IPF: Distinct horns of the same devil?,” Respiratory Research, Jan. 11, 2012, 13(1):3. [cited by applicant]
Chou, “Drug combination studies and their synergy quantification using the Chou-Talalay method,” Cancer Res., Jan. 2010, 70(2):440-446. [cited by applicant]
Chou, “Graphic rule for drug metabolism systems,” Current Drug Metabolism, May 2010, 11(4):369-378. [cited by applicant]
Christodoulides et al., “WNT10B mutations in human obesity,” Diabetologia, Apr. 2006, 49(4):678-684. [cited by applicant]
Clevers et al., “Wnt/β-catenin signaling in development and disease,” Cell, Nov. 3, 2006, 127(3):469-480. [cited by applicant]
Corr, “Wnt-beta-catenin signaling in the pathogenesis of osteoarthritis,” Nat. Clin. Pract Rheumatol., Oct. 2008, 4(10):550-556. [cited by applicant]
D'Alessio et al., “Benzodipyrazoles: a new class of potent CDK2 inhibitors,” Bioorganic & Medicinal Chemistry Letters, Mar. 1, 2005, 15(5):1315-1319. [cited by applicant]
Dann et al., “Insights into Wnt binding and signaling from the structures of two Frizzled cysteine-rich domains,” Nature, Jul. 2001, 412:86-90. [cited by applicant]
De Ferrari et al., “Wnt signaling function in Alzheimer's disease,” Brain Research Reviews, Aug. 2000, 33(1):1-12. [cited by applicant]
De Ferrari et al., “The ups and downs of Wnt signaling in prevalent neurological disorders,” Oncogene, Dec. 2006, 25(57):7545-7553. [cited by applicant]
De Ferrari et al., “Common genetic variation within the Low-Density Lipoprotein Receptor-Related Protein 6 and late-onset Alzheimer's disease,” Proc. Natl. Acad. Sci. USA, May 2007, 104(22):9434-9439. [cited by applicant]
Dermer, “Another Anniversary for the War on Cancer,” Nature Biotechnology, Mar. 1994, 12:320. [cited by applicant]
Dessalew et al., “3D-QSAR CoMFA and CoMSIA study on benzodipyrazoles as cyclin dependent kinase 2 inhibitors,” Medicinal Chemistry, Jul. 1, 2008, 4(4):313-321. [cited by applicant]
Dong et al., “QSAR study of Akt/protein kinase B (PKB) inhibitors using support vector machine,” European Journal of Medicinal Chemistry, Oct. 2009, 44(10):4090-4097. [cited by applicant]
Du Bois, “Strategies for treating idiopathic pulmonary fibrosis,” Nature Reviews Drug Discovery, Feb. 2010, 9(2):129-140. [cited by applicant]
Duncan et al., “The Clk2 and Clk3 dual-specificity protein kinases regulate the intranuclear distribution of SR proteins and influence pre-mRNA splicing,” Experimental Cell Research, Jun. 15, 1998, 241(2):300-308. [cited by applicant]
Edamoto et al., “Alterations of RB1, p53 and Wnt pathways in hepatocellular carcinomas associated with hepatitis C, hepatitis B and alcoholic liver cirrhosis,” Int J Cancer., Sep. 1, 2003, 106(3):334-341. [cited by applicant]
Egloff et al., “Gastrin-releasing peptide receptor expression in non-cancerous bronchial epithelia is associated with lung cancer: a case-control study,” Respiratory Research, Feb. 2012, 13:9. [cited by applicant]
Emami et al., “A small molecule inhibitor of ß-catenin/cyclic AMP response element-binding protein transcription,” Proceedings of the National Academy of Sciences, Aug. 24, 2004, 101(34):12682-12687. [cited by applicant]
Espada et al., “Wnt signalling and cancer stem cells,” Clin. Transl. Oncol., Jul. 15, 2009, 11(7):411-427. [cited by applicant]
Ewan et al., “A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription, ” Cancer Res., Jul. 15, 2010, 70(14):5963-5973. [cited by applicant]
Florez et al., “TCF7L2 Polymorphisms and Progression to Diabetes in the Diabetes Prevention Program,” N. Engl. J. Med., Jul. 2006, 355(3):241-250. [cited by applicant]
Freese et al., “Wnt signaling in development and disease,” Neurobiology of Disease, May 2010, 38(2):148-153. [cited by applicant]
Fujii et al., “An antagonist of dishevelled protein-protein interaction suppresses beta-catenin-dependent tumor cell growth,” Cancer Res., Jan. 2007, 67(2):573-579. [cited by applicant]
Fukuzawa et al., “Beckwith-Wiedemann Syndrome-associated Hepatoblastoma: Wnt Signal Activation Occurs Later in Tumorigenesis in Patients with 11p15.5 Uniparental Disomy,” Pediatric and Developmental Pathology, Jun. 20, … [cited by applicant]
Funnell et al., “CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor,” Nature Communications, Feb. 23, 2017, 8(1):1-16. [cited by applicant]
Giles et al., “Caught up in a Wnt storm: Wnt signaling in cancer,” Biochimica et Biophyssica Acta, Jun. 5, 2003, 1653(1):1-24. [cited by applicant]
Göckler et al., “Harmine specifically inhibits protein kinase DYRK1A and interferes with neurite formation, ” The FEBS Journal, Nov. 1, 2009, 276(21): 6324-6337. [cited by applicant]
Hanahan et al., “Hallmarks of cancer: the next generation,” Cell, Mar. 4, 2011, 144(5):646-674. [cited by applicant]
Hanahan et al., “The hallmarks of cancer,” Cell, Jan. 7, 2000, 100(1):57-70. [cited by applicant]
Handeli et al., “A small-molecule inhibitor of Tcf/beta-catenin signaling down-regulates PPARgamma and PPARdelta activities, ” Mol. Cancer Ther., Mar. 2008, 7(3):521-529. [cited by applicant]
Hayakawa et al., “Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo [1, 2-a] pyridines as novel PI3 kinase p110α inhibitors,” Bioorganic & medicinal chemistry, Sep. 1, 2007, 15(17):5837-5844. [cited by applicant]
Heinecke et al., “Tumor microenvironment-based feed-forward regulation of NOS2 in breast cancer progression,” Proceedings of the National Academy of Sciences, Apr. 29, 2014, 111(17):6323-6328. [cited by applicant]
Henderson Jr. et al., “Inhibition of Wnt/beta-catenin/CREB binding protein (CBP) signaling reverses pulmonary fibrosis,” Proc Natl Acad Sci U S A., Jul. 2010, 107(32):14309-14314. [cited by applicant]
Herbst et al., “Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling,” BMC Genomics, Dec. 1, 2014, 15(1):1-14. [cited by applicant]
Hsu et al., “The spliceosome is a therapeutic vulnerability in MYC-driven cancer,” Nature, Sep. 17, 2015, 525(7569):384-388. [cited by applicant]
Hu et al., “Discovery of indazoles as inhibitors of Tp12 kinase,” Bioorganic & Medicinal Chemistry Letters, Aug. 2011, 21(16):4758-4761. [cited by applicant]
Huang et al., “A molecular link between SR protein dephosphorylation and mRNA export,” Proceedings of the National Academy of Sciences, Jun. 29, 2004, 101(26):9666-9670. [cited by applicant]
Huang et al., “Tankyrase inhibition stabilizes axin and antagonizes Wnt signaling,” Nature, Oct. 2009, 461(7264):614-620. [cited by applicant]
Huang et al., “Synthesis of 3-(1H-benzimidazol-2-yl)-5-isoquinolin-4-ylpyrazolo[1,2- b]pyridine, a potent cyclin dependent kinase 1 (CDK1) inhibitor,” Bioorganic & Medicinal Chemistry Letters, Mar. 2007, 17(5):1243-1245. [cited by applicant]
Hübner et al., “Standardized quantification of pulmonary fibrosis in histological samples,” Biotechniques, Apr. 2008, 44(4):507-511 and 514-517. [cited by applicant]
Im et al., “Wnt inhibitors enhance chondrogenesis of human mesenchymal stem cells in a long-term pellet culture,” Biotechnol Lett., Jan. 2011, 33(5):1061-1068. [cited by applicant]
Inestrosa et al., “The role of Wnt signaling in neuronal dysfunction in Alzheimer's Disease,” Molecular Neurodegener, Dec. 2008, 3(9):1-13. [cited by applicant]
Isken et al “The multiple lives of NMD factors: balancing roles in gene and genome regulation,” Nature Reviews Genetics, Sep. 2008, 9(9):699-712. [cited by applicant]
Izumchenko et al., “Patient-derived xenografts as tools in pharmaceutical development,” Clinical Pharmacology & Therapeutics, Jun. 2016, 99(6):612-621. [cited by applicant]
Janssens et al., “The Wnt-dependent signaling pathways as target in oncology drug discovery,” Invest New Drugs., Jul. 2006, 24(4):263-280. [cited by applicant]
Jenkins et al., “Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis,” Nat. Genet., Jan. 2009, 41(1):95-100. [cited by applicant]
Jessen et al., “Peripheral white blood cell toxicity induced by broad spectrum cyclin-dependent kinase inhibitors,” Journal of Applied Toxicology, Jan. 2007, 27(2):133-142. [cited by applicant]
Johnson et al., “A stem cell-based approach to cartilage repair,” Science, Apr. 5, 2012, 336(6082):717-721. [cited by applicant]
Kahn, “Can we safely target the WNT pathway?” Nature Reviews Drug discovery, Jul. 2014, 13(7):513-532. [cited by applicant]
Kanazawa et al., “Association of the Gene Encoding Wingless-Type Mammary Tumor Virus Integration-Site Family Member 5B (WNT5B) with Type 2 Diabetes,” Am. J. Hum. Genet., Nov. 2004, 75(5):832-843. [cited by applicant]
Karlberg et al., “Structural basis for the interaction between tankyrase-2 and a potent Wnt-signaling inhibitor,” J. Med. Chem., Jun. 21, 2010, 53(14):5352-5355. [cited by applicant]
Kibar et al., “Mutations in VANGL1 Associated with Neural-Tube Defects,” N. Engl. J. Med., Apr. 2007, 356(14):1432-1437. [cited by applicant]
Kim et al., “Proof-of-Principle: Oncogenic B-Catenin Is a Valid Molecular Target for the Development of Pharmacological Inhibitors 1 Supported by NIH Grants K01 CA87828, R55 CA95736, and R01 CA095736 and the Lombardi Ca… [cited by applicant]
Kuwajima et al., “Necdin Promotes GABAergic Neuron Differentiation in Cooperation with Dlx Homeodomain Proteins,” Journal of Neuroscience, May 2006, 26(20):5383-5392. [cited by applicant]
Kwong et al., “APC and its modifiers in colon cancer,” Adv. Exp. Med. Biol., 2009, 656:85-106. [cited by applicant]
Lammi et al., “Mutations in AXIN2 Cause Familial Tooth Agenesis and Predispose to Colorectal Cancer,” Am. J. Hum. Genet., May 2004, 74(5):1043-1050. [cited by applicant]
Lamond et al., “Nuclear speckles: a model for nuclear organelles,” Nature Reviews Molecular Cell Biology, Aug. 2003, 4(8):605-612. [cited by applicant]
Le Guellec et al., “CTNNB1 mutation analysis is a useful tool for the diagnosis of desmoid tumors: a study of 260 desmoid tumors and 191 potential morphologic mimics, ” Modern Pathology, Dec. 2012, 25(12):1551-1558. [cited by applicant]
Lenz et al., “Safely targeting cancer stem cells via selective catenin coactivator antagonism,” Cancer Science, Sep. 2014, 105(9):1087-1092. [cited by applicant]
Li et al., “Artesunate attenuates the growth of human colorectal carcinoma and inhibits hyperactive Wnt/beta-catenin pathway,” Int J Cancer., Sep. 2007, 121(6):1360-1365. [cited by applicant]
Lin et al., “Synthesis and evaluation of pyrazolo[3,4-b]pyridine CDK1 inhibitors as anti-tumor agents,” Bioorganic & Medicinal Chemistry Letters, Aug. 2007, 17(15):4297-4302. [cited by applicant]
Long et al., “The SR protein family of splicing factors: master regulators of gene expression,” Biochemical Journal, Jan. 1, 2009, 417(1):15-27. [cited by applicant]
Lories et al., “To Wnt or not to Wnt: the bone and joint health dilemma,” Nature Reviews Rheumatol., Mar. 2013, 9(6):328-339. [cited by applicant]
Low et al., “Phenotypic fingerprinting of small molecule cell cycle kinase inhibitors for drug discovery,” Curr Chem Genomics., Mar. 2009, 3:13-21. [cited by applicant]
Lu et al., “Structure-activity relationship studies of small-molecule inhibitors of Wnt response,” Bioorganic & Medicinal Chemistry Letters, Jul. 2009, 19(14):3825-3827. [cited by applicant]
Luo et al., “Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells,” PLoS Genetics, Apr. 8, 2010, 6(4):e1000898. [cited by applicant]
Luu et al., “Wnt/beta-catenin signaling pathway as a novel cancer drug target,” Curr. Cancer Drug Targets., Dec. 2004, 4(8):653-671. [cited by applicant]
Luyten et al., “Wnt signaling and osteoarthritis,” Bone, Apr. 1, 2009, 44(4):522-527. [cited by applicant]
Ma et al., “Differential roles for the coactivators CBP and p300 on TCF/B-catenin-mediated survivin gene expression,” Oncogene, May 2005, 24(22):3619-3631. [cited by applicant]
MacDonald et al., “Wnt/beta-catenin signaling: components, mechanisms, and diseases,” Developmental Cell, Jul. 21, 2009, 17(1):9-26. [cited by applicant]
Mallinger et al., “2,8-Disubstituted-1, 6-Naphthyridines and 4, 6-Disubstituted- Isoquinolines with Potent, Selective Affinity for CDK8/19,” Acs Medicinal Chemistry, Jun. 9, 2016, 7(6):573-578. [cited by applicant]
Mandel et al., “SERKAL Syndrome: An Autosomal-Recessive Disorder Caused by a Loss-of-Function Mutation in WNT4,” The American Journal of Human Genetics, Jan. 10, 2008, 82(1):39-47. [cited by applicant]
Mani et al., “LRP6 Mutation in a Family with Early Coronary Disease and Metabolic Risk Factors,” Science, Mar. 2, 2007, 315(5816):1278-1282. [cited by applicant]
Mazzoni et al., “AXIN1 and AXIN2 variants in gastrointestinal cancers,” Cancer Letters, Dec. 1, 2014, 355(1):1-8. [cited by applicant]
McBride et al. “Design and structure-activity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases,” Bioorganic & Medicinal Chemistry Letters, Jul. 1, 2006, 16(13):3595-3599. [cited by applicant]
Misra et al., “1H-Pyrazolo[3,4-b]pyridine inhibitors of cyclin-dependent kinases: highly potent 2,6-Difluorophenacyl analogues,” Bioorganic & Medicinal Chemistry Letters, Jul. 21, 2003, 13(14):2405-2408. [cited by applicant]
Moon et al., “WNT and β-catenin signalling: diseases and therapies,” Nature Reviews Genetics, Sep. 2004, 5(9):689-699. [cited by applicant]
Morrisey, “Wnt signaling and pulmonary fibrosis,” The American Journal of Pathology, May 1, 2003, 162(5): 1393-1397. [cited by applicant]
Muddassar et al., “Elucidation of binding mode and three dimensional quantitative structure-activity relationship studies of a novel series of protein kinase B/Akt inhibitors,” Journal of Molecular Modeling, Nov. 2008, … [cited by applicant]
Niemann et al., “Homozygous WNT3 Mutation Causes Tetra-Amelia in a Large Consanguineous Family,” The American Journal of Human Genetics, Mar. 1, 2004, 74(3):558-563. [cited by applicant]
Nishisho et al., “Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients,” Science, Aug. 9, 1991, 253(5020):665-669. [cited by applicant]
Notice of Allowance for U.S. Appl. No. 15/884,112, mailed on Jul. 5, 2018, 8 pages. [cited by applicant]
Nusse et al., “Three decades of Wnts: a personal perspective on how a scientific field developed,” The EMBO Journal, Jun. 13, 2012, 31(12):2670-2684. [cited by applicant]
Nusse, “Wnt signaling in disease and in development,” Cell Research, Jan. 2005, 15(1):28-32. [cited by applicant]
Oates et al., “Increased DNA Methylation at the AXIN1 Gene in a Monozygotic Twin from a Pair Discordant for a Caudal Duplication Anomaly,” The American Journal of Human Genetics, Jul. 1, 2006, 79(1):155-162. [cited by applicant]
Oduor et al., “Trypanosoma brucei glycogen synthase kinase-3, a target for anti-trypanosomal drug development: a public-private partnership to identify novel leads,” PLoS Neglected Tropical Diseases, Apr. 5, 2011, 5(4):… [cited by applicant]
O'keefe et al., “Disruption of pre-mRNA splicing in vivo results in reorganization of splicing factors,” The Journal of Cell Biology, Feb. 1, 1994, 124(3):249-260. [cited by applicant]
Okerlund et al., “Synaptic Wnt signaling-a contributor to major psychiatric disorders?,” Journal of Neurodevelopmental Disorders, Apr. 28, 2011, 3(2):162-174. [cited by applicant]
Polakis, “Wnt signaling and cancer,” Genes & Development, Aug. 1, 2000, 14(15):1837-1851. [cited by applicant]
Pubchem, Substance Record for SID 164345938, Deposit Nov. 4, 2013, retrieved on Nov. 16, 2015, retrieved from URL <https://pubchem.ncbi.nlm.nih.gov/substance/164345938>, 5 pages. [cited by applicant]
Qin et al., “Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes,” Human Mutation, Aug. 2005, 26(2):104-112. [cited by applicant]
Reya et al., “Wnt signalling in stem cells and cancer,” Nature, Apr. 14, 2005, 434(7035):843-850. [cited by applicant]
Richards et al., “Peripheral blood proteins predict mortality in idiopathic pulmonary fibrosis,” American Journal of Respiratory and Critical Care Medicine, Jan. 1, 2012, 185(1):67-76. [cited by applicant]
Riggs et al., “The discovery of a dual TTK protein kinase/CDC2-like kinase (CLK2) inhibitor for the treatment of triple negative breast cancer initiated from a phenotypic screen,” Journal of Medicinal Chemistry, Nov. 9,… [cited by applicant]
Rivera et al., “An X Chromosome Gene, WTX, Is Commonly Inactivated in Wilms Tumor,” Science, Feb. 2, 2007, 315(5812):642-645. [cited by applicant]
Robitaille et al., “Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy,” Nature Genetics, Oct. 1, 2002, 32(2):326-330. [cited by applicant]
Ryu et al., “Natural derivatives of curcumin attenuate the Wnt/beta-catenin pathway through down-regulation of the transcriptional coactivator p300,” Biochemical and biophysical research communications, Dec. 26, 2008, 3… [cited by applicant]
Salinas, “Wnt signaling in the vertebrate central nervous system: from axon guidance to synaptic function,” Cold Spring Harbor Perspectives in Biology, Feb. 1, 2012, 4(2):a008003. [cited by applicant]
Sato, “Upregulation of the Wnt/beta-catenin pathway induced by transforming growth factor-beta in hypertrophic scars and keloids,” Acta Dermato-Venereologica, Jul. 29, 2006, 86(4):300-307. [cited by applicant]
Seah et al., “Neuronal Death Resulting from Targeted Disruption of the Snf2 Protein ATRX Is Mediated by p53,” Journal of Neuroscience, Nov. 19, 2008, 28(47):12570-12580. [cited by applicant]
Shih et al., “Pharmacophore modeling and virtual screening to identify potential RET kinase inhibitors, ” Bioorganic & Medicinal Chemistry Letters, Jun. 12, 2011, 21(15):4490-4497. [cited by applicant]
Shruster et al., “Wnt signaling enhances neurogenesis and improves neurological function after focal ischemic injury,” PLoS One, Jul. 17, 2012, 7(7):e40843, 11 pages. [cited by applicant]
Silva et al., “Advances in Prodrug Design,” Mini-Revs. In Med. Chem., Oct. 2005, 5(10):893-914. [cited by applicant]
Slattery et al., “Expression of Wnt-signaling pathway genes and their associations with miRNAs in colorectal cancer,” Oncotarget, Jan. 19, 2018, 9(5):6075-6085. [cited by applicant]
Smith et al., “Processing of endogenous pre-mRNAs in association with SC-35 domains is gene specific, ” The Journal of Cell Biology, Feb. 22, 1999, 144(4):617-629. [cited by applicant]
Solowiej et al., “Characterizing the Effects of the Juxtamembrane Domain on Vascular Endothelial Growth Factor Receptor-2 Enzymatic Activity, Autophosphorylation, and Inhibition by Axitinib,” Biochemistry, Jul. 28, 2009… [cited by applicant]
Starosyla et al., “ASK1 pharmacophore model derived from diverse classes of inhibitors,” Bioorganic & Medicinal Chemistry Letters, Sep. 15, 2014, 24(18):4418-4423. [cited by applicant]
Stojdl et al., “SR protein kinases: the splice of life,” Biochemistry and Cell Biology, Aug. 25, 1999, 77(4):293-298. [cited by applicant]
Sutherland et al., “A robust high-content imaging approach for probing the mechanism of action and phenotypic outcomes of cell-cycle modulators,” Molecular Cancer Therapeutics, Feb. 1, 2011, 10(2):242-254. [cited by applicant]
Swaney et al., “A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model,” British Journal of Pharmacology, Aug. 2010, 160(7):1699-1713. [cited by applicant]
Takahashi-Yanaga et al., “Celecoxib-induced degradation of T-cell factors-1 and -4 in human colon cancer cells,” Biochemical Biophysical Research Communications, Nov. 5, 2008, 377(4):1185-1190. [cited by applicant]
Tamamura et al., “Developmental regulation of Wnt/beta-catenin signals is required for growth plate assembly, cartilage integrity, and endochondral ossification,” J Biol Chem., Mar. 2005, 280(19):19185-19195. [cited by applicant]
Terao et al., “Design and biological evaluation of imidazo [1, 2-a] pyridines as novel and potent ASK1 inhibitors,” Bioorganic & Medicinal Chemistry Letters, Oct. 23, 2012, 22(24):7326-7329. [cited by applicant]
The Cancer Genome Atlas Network, “Comprehensive molecular characterization of human colon and rectal cancer,” Nature, 2021, 487(7407):330-337. [cited by applicant]
Thomas et al., “Identification of a novel 3, 5-disubstituted pyridine as a potent, selective, and orally active inhibitor of Akt1 kinase,” Bioorganic & Medicinal Chemistry Letters, Jul. 15, 2006, 16(14):3740-3744. [cited by applicant]
Thompson et al., “WNT/beta-catenin signaling in liver health and disease,” Hepatology, May 2007, 45(5):1298-1305. [cited by applicant]
Trujillo et al., “2-(6-Phenyl-1H-indazol-3-y1)-1H-benzo[d]imidazoles: design and synthesis of a potent and isoform selective PKC-zeta inhibitor,” Bioorg Med Chem Lett., Dec. 6, 2008, 19(3):908-911. [cited by applicant]
Ugur et al., “Homozygous WNT10b mutation and complex inheritance in Split-Hand/Foot Malformation,” Human Molecular Genetics, Apr. 7, 2008, 17(17):2644-2653. [cited by applicant]
Vacik et al., “Dominant-negative isoforms of Tcf/Lef proteins in development and disease,” Cell Cycle, Dec. 15, 2011, 10(24):4199-4200. [cited by applicant]
Vulpetti et al., “Structure-based approaches to improve selectivity: CDK2—GSK3β binding site analysis,” Journal of Chemical Information and Modeling, Jan. 26, 2005, 45(5):1282-1290. [cited by applicant]
Wagner et al., “The therapeutic potential of the Wnt signaling pathway in bone disorders,” Current Molecular Pharmacology, Jan. 1, 2011, 4(1):14-25. [cited by applicant]
Wainberg et al., “Lapatinib, a dual EGFR and HER2 kinase inhibitor, selectively inhibits HER2-amplified human gastric cancer cells and is synergistic with trastuzumab in vitro and in vivo,” Clinical Cancer Research, Mar… [cited by applicant]
Walters et al., “Mouse models of bleomycin-induced pulmonary fibrosis,” Current Protocols in Pharmacology, 2008, Chapter 5: Unit 5.46, 17 pages. [cited by applicant]
Wang et al., “A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication, ” Nature Medicine, Mar. 9, 2015, 21(4):383-388. [cited by applicant]
Wang et al., “Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia,” Nature Genetics, Jul. 3, 2007, 39(7):836-838. [cited by applicant]
Wantanabe and Dai, “Winning WNT: race to Wnt signaling inhibitors,” Proceedings of the National Academy of Sciences, Apr. 12, 2011, 108(15):5929-5930. [cited by applicant]
Weng et al., “Control of Dkk-1 ameliorates chondrocyte apoptosis, cartilage destruction, and subchondral bone deterioration in osteoarthritic knees,” Arthritis & Rheumatism, May 2010, 62(5):1393-1402. [cited by applicant]
Witherington et al., “5-Aryl-pyrazolo[3,4-b]pyridazines: potent inhibitors of glycogen synthase kinase-3 (GSK-3),” Bioorganic & Medicinal Chemistry Letters, May 5, 2003, 13(9):1581-1584. [cited by applicant]
Woods et al., “Mutations in WNT7A Cause a Range of Limb Malformations, Including Fuhrmann Syndrome and Al-Awadi/Raas-Rothschild/Schinzel Phocomelia Syndrome,” The American Journal of Human Genetics, Aug. 1, 2006, 79(2):… [cited by applicant]
Yang et al., “Wnt modulates MCL1 to control cell survival in triple negative breast cancer,” BMC Cancer, Dec. 2014, 14(1):1-3. [cited by applicant]
Yardy et al., “Wnt signalling and prostate cancer,” Prostate Cancer Prostatic Diseases, Jun. 2005, 8(2):119-126. [cited by applicant]
Yoshida et al., “CLK2 is an oncogenic kinase and splicing regulator in breast cancer,” Cancer Research, Apr. 1, 2015, 75(7):1-12. [cited by applicant]
Zhang et al., “Small-molecule synergist of the Wnt/beta-catenin signaling pathway,” Proceedings of the National Academy of Sciences, May 1, 2007, 104(18):7444-7448. [cited by applicant]
Zhong et al., “Characterization of in vitro and in vivo metabolism of AG-024322, a novel cyclin-dependent kinase (CDK) inhibitor,” Health, Nov. 16, 2009), 1(4):249-262. [cited by applicant]
Zhou et al., “Regulation of splicing by SR proteins and SR protein-specific kinases,” Chromosoma, Mar. 24, 2013, 122(3):1-28. [cited by applicant]