IP Library › Granted Patent US 12,570,679
Granted Patent B2
US 12,570,679 · App. 17/442,726 · Granted Mar 10, 2026

STAT3 protein degraders

Inventors: Shaomeng Wang (Superior Township, MI); Haibin Zhou (Ann Arbor, MI); Renqi Xu (Ann Arbor, MI)
Assignee: REGENTS OF THE UNIVERSITY OF MICHIGAN
C07F9/6561A61P35/00C07F9/65583C07F9/65586
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,570,679
App. No.
17/442,726
Granted
Mar 10, 2026
Kind
B2
Abstract

The present disclosure provides compounds represented by Formulae I and IV: wherein R 1a , R 1b , R 2a , R 2b , A, E, Q D , and Q E are as defined in the specification, and the salts and solvates thereof. Compounds of Formula I are degraders of STAT3. Compounds of Formula IV are inhibitors of STAT3. STAT3 degraders and inhibitors are useful for the treatment of cancer and other diseases.

Claims (91)

1 . A compound of Formula I:

or a pharmaceutically acceptable salt or solvate thereof, wherein:

R 1a and R 1b are each independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and —CH 2 OC(═O)R 1e ;

R 1e is C 1 -C 6 alkyl;

R 2a and R 2b are each fluoro; or

R 2a and R 2b taken together with the carbon atom to which they are attached form a —C(═O)— group;

A is selected from the group consisting of:

G 1 is selected from the group consisting of —O—, —S—, and —NR 17 —;

G 2 is selected from the group consisting of —N═ and —CR 18a ═;

G 3 is selected from the group consisting of —N═ and —CR 18b ═;

R 3 is selected from the group consisting of hydrogen, halo, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, —C(═O)R 3a , and (C 6 -C 14 aryl)C 1 -C 6 alkyl;

R 17 is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, (C 6 -C 14 aryl)C 1 -C 6 alkyl, and —C(═O)R 17a ;

R 17a is C 1 -C 4 alkyl;

R 18a and R 18b are each independently selected from the group consisting of hydrogen, halo, and C 1 -C 4 alkyl,

wherein the bond designated with an “*” is attached to —C(═O)-E-Q D ;

E is

wherein the bond of E-8 designated with an “*” is attached to Q D ;

R 3g is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 4m is selected from the group consisting of hydrogen, halo, and C 1 -C 4 alkyl;

R 4n is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 4o and R 4p are each independently selected from the group consisting of hydrogen and C 1 -C 4 alkyl; or

R 4o and R 4p taken together with the carbon atom to which they are attached form a —C(═O)— group;

Q D is selected from the group consisting of:

X 4 is selected from the group consisting of —CH 2 —, —O—, and —N(R 11d )—; or

X 4 is absent;

v is 0, 1, 2, 3, or 4;

R 12d is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and (C 6 -C 14 aryl)C 1 -C 6 alkyl;

R 13a is selected from the group consisting of hydrogen, C 1 -C 6 alkyl, optionally substituted C 3 -C 12 cycloalkyl, optionally substituted C 6 -C 14 aryl, (C 6 -C 14 aryl)C 1 -C 6 alkyl, and optionally substituted 5- to 9-membered heteroaryl;

R 13b is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 13c is selected from the group consisting of hydrogen and C 1 -C 4 alkyl; or

R 13a and R 13b taken together form a optionally substituted C 3 -C 8 cycloalkyl or optionally substituted 4- to 9-membered heterocyclo; or

R 13b and R 13c taken together form a optionally substituted 4- to 9-membered heterocyclo;

A 2 of Q-6 is selected from the group consisting of —C(R 14b )— and —N—;

R 14b is selected from the group consisting of hydrogen and C 1 -C 3 alkyl;

g is 1, 2, or 3;

h is 1, 2, or 3;

L is -J 1 -Y 1 -J 2 -Y 2 -J 3 -Z—;

J 1 is selected from the group consisting of C 1 -C 12 alkylenyl, 3- to 20-membered heteroalkylenyl, C 4 -C 6 cycloalkylenyl, 4- to 8-membered heterocyclenyl, phenylenyl, and 5- to 9-membered heteroarylenyl; or

J 1 is absent;

Y 1 is selected from the group consisting of —(CH 2 ) m —, —C≡C—, —CH≡CH—, —N(R 16 a)-, —C(═O)—, —S(═O) 2 —, —C(═O)O—, —OC(═O)—, —C(═O)N(R 16b )—, and —N(R 16b ) C(═O)—;

m is 0, 1, 2, or 3;

R 16a is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and (C 6 -C 14 aryl) C 1 -C 6 alkyl;

R 16b is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

J 2 is selected from the group consisting of C 1 -C 12 alkylenyl, 3- to 20-membered heteroalkylenyl, C 4 -C 6 cycloalkylenyl, 4- to 8-membered heterocyclenyl, phenylenyl, and 5- to 9-membered heteroarylenyl; or

J 2 is absent;

Y 2 is selected from the group consisting of —(CH 2 ) n —, —C≡C—, —CH═CH—, —N(R 16a ′)—, —C(═O)—, —S(═O) 2 —, —C(═O)O—, —OC(═O)—, —C(═O)N(R 16b ′), and —N(R 16b ′) C(═O)—;

n is 0, 1, 2, 3, 4, 5, or 6;

R 16a ′ is selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and (C 6 -C 14 aryl)C 1 -C 6 alkyl;

R 16b ′; is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

J 3 is selected from the group consisting of C 1 -C 12 alkylenyl, 3- to 20-membered heteroalkylenyl, C 4 -C 6 cycloalkylenyl, 4- to 8-membered heterocyclenyl, phenylenyl, and 5- to 9-membered heteroarylenyl; or

J 3 is absent;

Z is selected from the group consisting of —(CH 2 ) d —, —C≡C—, —CH—CH—, —C(═O)—, —O—, —S—, —N(R 16c )—, —C(═O)N(R 16d )—, —N(R 16d ) C(═O)—, —N(R 16e ) C(═O)CH 2 O—,

and —N(R 16f ) C(═O)CH 2 N(R 16g )—;

d is 0, 1, 2, or 3;

R 16c , R 16d , R 16e , R 16f , and R 16g are each independently selected from the group consisting of hydrogen, C 1 -C 4 alkyl, and (C 6 -C 14 aryl)C 1 -C 6 alkyl;

wherein Z is attached to B;

B is selected from the group consisting of:

A 5 is selected from the group consisting of —C(R 19a )═ and —N═;

A 2 of B-1, B-3, and B-4 is selected from the group consisting of —C(R 19b )═ and —N═;

A 3 is selected from the group consisting of —C(R 19c )═ and —N═;

A 4 is selected from the group consisting of —C(R 19 d)═ and —N═;

Z 1 is selected from the group consisting of —CH 2 and —C(—O)—;

R 5a of B-1, B-2, B-3, and B-4 is selected from the group consisting of hydrogen, methyl, and fluoro;

R 5b of B-1, B-2, B-3, and B-4 is selected from the group consisting of hydrogen and methyl;

R 19a , R 19b , R 19c , and R 19d are each independently selected from the group consisting of hydrogen, halo, and C 1-4 alkyl;

R 20 is C 1 -C 6 alkyl;

R 21 is selected from the group consisting of hydrogen and C 1 -C 4 alkyl;

R 22a is selected from the group consisting of C 1 -C 6 alkyl and optionally substituted C 3 -C 6 cycloalkyl;

R 22b is selected from the group consisting of C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted C 6 -C 14 aryl, and optionally substituted 5- to 14-membered heteroaryl;

R 23 is selected from the group consisting of C 1 -C 6 alkyl and optionally substituted C 3 -C 6 cycloalkyl; and

R 24 is selected from the group consisting of C 1 -C 6 alkyl, optionally substituted C 3 -C 6 cycloalkyl, optionally substituted C 6 -C 14 aryl, and optionally substituted 5- to 14-membered heteroaryl.

2 . The compound of claim 1 , wherein A is selected from the group consisting of:

3 . The compound of claim 2 , wherein A is:

4 . The compound of claim 1 , wherein R 2a and R 2b are each fluoro.

5 . The compound of claim 1 , wherein

E-8 is selected from the group consisting of:

6 . The compound of claim 1 , wherein L is —Y 1 -J 2 -Y 2 -J 3 -Y 2 —, —Y 1 -Y 2 -J 3 Z—, —Y 1 -J 2 -Y 2 —Z—, or —Y 1 -Y 2 —Z—.

7 . The compound of claim 6 , wherein Y 1 is selected from the group consisting of —(CH 2 ) m — and —C(═O)—; m is 1, 2, or 3; Y 2 is —(CH 2 ) n —; n is 1, 2, 3, 4, 5, or 6; and Z is selected from the group consisting of —(CH 2 )—, —C≡C—, and —N(H)—.

8 . The compound of claim 1 , wherein B is B-1, and B-1 is:

or a pharmaceutically acceptable salt or solvate thereof.

9 . The compound of claim 1 , wherein R 1a and R 1b are each hydrogen.

10 . The compound of claim 1 , wherein the compound is selected from:

or a pharmaceutically acceptable salt or solvate thereof.

11 . A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

12 . The compound of claim 1 , wherein Q-5 is Q-5-1 or Q-5-2:

or a pharmaceutically acceptable salt or solvate thereof.

13 . The compound of claim 12 , wherein X 4 is —CH 2 —and v is 0, or a pharmaceutically acceptable salt or solvate thereof.

14 . The compound of claim 12 , wherein R 12d is hydrogen, or a pharmaceutically acceptable salt or solvate thereof.

15 . The compound of claim 12 , wherein R 13a is selected from the group consisting of optionally substituted C 3 -C 12 cycloalkyl, aralkyl, and optionally substituted phenyl, or a pharmaceutically acceptable salt or solvate thereof.

16 . The compound claim 1 , wherein Q-6 is Q-6-1 or Q-6-2:

or a pharmaceutically acceptable salt or solvate thereof.

Continuity (2)
Provisional Application 62826492 · Mar 29, 2019
Related Publication 20220185831A1 · Jun 16, 2022
References Cited (110)
US 5093330A · Caravatti et al. · 1992 [cited by applicant]
US 6207156B1 · Kuchroo et al. · 2001 [cited by applicant]
US 6808710B1 · Wood et al. · 2004 [cited by applicant]
US 6984720B1 · Korman et al. · 2006 [cited by applicant]
US 7595048B2 · Honjo et al. · 2009 [cited by applicant]
US 8008449B2 · Korman et al. · 2011 [cited by applicant]
US 8114845B2 · Langermann et al. · 2012 [cited by applicant]
US 8217149B2 · Irving et al. · 2012 [cited by applicant]
US 8522156B2 · Kumagai et al. · 2013 [cited by applicant]
US 8728474B2 · Honjo et al. · 2014 [cited by applicant]
US 8779105B2 · Korman et al. · 2014 [cited by applicant]
US 8900587B2 · Carven et al. · 2014 [cited by applicant]
US 8907053B2 · Sasikumar et al. · 2014 [cited by applicant]
US 8952136B2 · Carven et al. · 2015 [cited by applicant]
US 9073994B2 · Honjo et al. · 2015 [cited by applicant]
US 9084776B2 · Korman et al. · 2015 [cited by applicant]
US 11485750B1 · Mainolfi · 2022 [cited by examiner]
US 11746120B2 · Mainolfi · 2023 [cited by examiner]
US 12077555B2 · Mainolfi · 2024 [cited by examiner]
US 20070010428A1 · McMurray et al. · 2007 [cited by applicant]
US 20110150892A1 · Thudium et al. · 2011 [cited by applicant]
US 20130022623A1 · Karsunky et al. · 2013 [cited by applicant]
US 20130071403A1 · Rolland et al. · 2013 [cited by applicant]
US 20130309250A1 · Cogswell et al. · 2013 [cited by applicant]
US 20140093511A1 · Lonberg et al. · 2014 [cited by applicant]
US 20140286935A1 · Hamblin et al. · 2014 [cited by applicant]
US 20140341917A1 · Nastri et al. · 2014 [cited by applicant]
US 20150225457A1 · Blumberg et al. · 2015 [cited by applicant]
US 20150250853A1 · Mak · 2015 [cited by applicant]
US 20150259420A1 · Triebel et al. · 2015 [cited by applicant]
US 20220185831A1 · Wang et al. · 2022 [cited by applicant]
US 20230083015A1 · Wang et al. · 2023 [cited by applicant]
US 20230133504A1 · Reddy et al. · 2023 [cited by applicant]
US 20230159573A1 · Wang et al. · 2023 [cited by applicant]
WO WO2010077589A2 · 2010 [cited by applicant]
WO WO2010118309A2 · 2010 [cited by applicant]
WO WO2015036499A1 · 2015 [cited by applicant]
WO WO2015127548A1 · 2015 [cited by applicant]
WO WO2019036815A1 · 2019 [cited by applicant]
WO WO2020198435A1 · 2020 [cited by applicant]
WO WO2020205467A1 · 2020 [cited by applicant]
WO WO2020206424A1 · 2020 [cited by applicant]
WO WO2021016333A1 · 2021 [cited by applicant]
WO WO2021195481A1 · 2021 [cited by applicant]
WO WO2021188696A1 · 2021 [cited by applicant]
WO WO2022182395A1 · 2022 [cited by applicant]
WO WO2023250058A1 · 2023 [cited by applicant]
WO WO2024148041A1 · 2024 [cited by applicant]
WO WO2024173291A1 · 2024 [cited by applicant]
WO WO2024173298A1 · 2024 [cited by applicant]
Mandal (Organic Letters vol. 11 pp. 3394-3397, published 2009) (Year: 2009). [cited by examiner]
Communication from Examining Division, dated Nov. 2, 2022, for European Patent Application No. 20719095.0 (5 total pages). [cited by applicant]
International Preliminary Report on Patentability, mailed Oct. 14, 2021, for International Application No. PCT/US2020/025116 (10 pages). [cited by applicant]
International Preliminary Report on Patentability, mailed Oct. 6, 2022, for International Application No. PCT/US2021/024332 (9 total pages). [cited by applicant]
International Preliminary Report on Patentability, mailed Oct. 7, 2021, for International Application No. PCT/US2020/024892 (15 total pages). [cited by applicant]
Anderson, A. C., “Tim-3: an emerging target in the cancer immunotherapy landscape” Cancer Immunology Research, (2014); 2(5):393-398. [cited by applicant]
Bai et al., “Targeted Degradation of BET Proteins in Triple-Negative Breast Cancer” Cancer Res., (2017); 77(9):2476-2487. [cited by applicant]
Banerjee et al., “Constitutive activation of STAT3 in breast cancer cells: A review” Int. J. Cancer, (2016); 138(11):2570-2578. [cited by applicant]
Betts, B.C. et al., “CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response,” Journal of Leukocyte Biology, (Apr. 2015); 97:807-… [cited by applicant]
Bingham et al., “Over one hundred solvates of sulfathiazole Electronic supplementary information (ESI) available: solvates and adducts of sulfathiazole,” Chemical Communications, (Mar. 13, 2001); Issue 7, pp. 603-604. [cited by applicant]
Bondeson, D. P., et al., “Catalytic in vivo protein knockdown by small-molecule PROTACS”, Nature Chemical Biology (2015); 11(8): 611-617. [cited by applicant]
Caira et al., “Preparation and Crystal Characterization of a Polymorph, a Monohydrate, and an Ethyl Acetate Solvate of the Antifungal Fluconazole” J. Pharm. Sci., (Mar. 2004); 93(3):601-611. [cited by applicant]
Fischer, E.S. et al., “Structure of the DDB1-CRBN E3 Ubiquitin ligase in complex with thalidomide”, Nature (2014); 512(7512):49-53. [cited by applicant]
Haura et al., “Mechanisms of disease: Insights into the emerging role of signal transducers and activators of transcription in cancer” Nat Clin Pract Oncol, (Jun. 2005); 2(6):315-324. doi: 10.1038/ncponc0195. [cited by applicant]
Huang et al., “Role of LAG-3 in regulatory T cells” Immunity, (2004); 21(4):503-513. [cited by applicant]
Johnson et al., “Targeting the IL-6/JAK/STAT3 signalling axis in cancer” Nat Rev Clin Oncol, (Apr. 2018); 15(4):234-248. doi: 10.1038/nrclinonc.2018.8. Epub Feb. 6, 2018. [cited by applicant]
Kortylewski et al., “Targeting STAT3 affects melanoma on multiple fronts” Cancer Metastasis Rev, (Jun. 2005); 24(2):315-327. doi: 10.1007/s10555-005-1580-1. [cited by applicant]
Laurence, A. et al., “STAT3 transcription factor promotes instability of nTreg cells and limits generation of iTreg cells during acute murine graft-versus-host disease” Immunity, (Aug. 2012); 37(2):209-22. doi: 10.1016/… [cited by applicant]
Löb et al., IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism' Cancer Immunol. Immunother., (2009); 58(1):153-157. [cited by applicant]
Li et al., “Discovery of MD-224 as a First-in-Class, Highly Potent, and Efficacious Proteolysis Targeting Chimera Murine Double Minute 2 Degrader Capable of Achieving Complete and Durable Tumor Regression” J Med Chem, (… [cited by applicant]
Lu, S.X et al., “STAT-3 and ERK 1/2 phosphorylation are critical for T-cell alloactivation and graft-versus-host disease,” Blood, (Dec. 15, 2008); 112(13):5254-5258, DOI 10.1182/blood-2008-03-147322. [cited by applicant]
Miklossy, G. et al., “Therapeutic modulators of STAT signalling for human diseases” Nature Reviews Drug Discovery, (2013); 12(8):611-629. [cited by applicant]
Morlacchi et al., “Synthesis and in Vitro Evaluation of a Peptidomimetic Inhibitor Targeting the Src Homology 2 (SH2) Domain of STAT6” ACS Med Chem Lett, (Dec. 4, 2013); 5(1):69-72. doi: 10.1021/ml4003919. [cited by applicant]
Naido et al., “Immune modulation for cancer therapy” British Journal of Cancer, (2014); 111(12):2214-2219. [cited by applicant]
Ngiow et al., “Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors” Cancer Res, (May 2011); 71(10):3540-51. doi: 10.1158/0008-5472.CAN-11-0096. Epub Mar. 23, 2011. [cited by applicant]
Ngiow et al., “Prospects for TIM3-Targeted Antitumor Immunotherapy” Cancer Res., (2011); 71(21):6567-6571. [cited by applicant]
Pardoll, “The blockade of immune checkpoints in cancer immunotherapy” Nat. Rev. Cancer, (2012); 12(4):252-264. [cited by applicant]
Qian et al., “Efficacy of levo-1-methyl tryptophan and dextro-1-methyl tryptophan in reversing indoleamine-2,3-dioxygenase-mediated arrest of T-cell proliferation in human epithelial ovarian cancer” Cancer Res., (2009);… [cited by applicant]
Qin et al., “Discovery of QCA570 as an Exceptionally Potent and Efficacious Proteolysis Targeting Chimera (PROTAC) Degrader of the Bromodomain and Extra-Terminal (BET) Proteins Capable of Inducing Complete and Durable T… [cited by applicant]
Radojcic, V. et al., “STAT3 Signaling in CD4+ T Cells Is Critical for the Pathogenesis of Chronic Sclerodermatous Graft-Versus-Host Disease in a Murine Model,” The Journal of Immunology, (2010); 184(2):764-774, https://… [cited by applicant]
Raina, K. et al., “Chemical Inducers of Targeted Protein Degradation”, Journal of Biological Chemistry (2010); 285(15):11057-11060. [cited by applicant]
Raina, K. et al., “PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer”, Proceedings of the National Academy of Sciences (2016); 113(26):7124-7129. [cited by applicant]
Sakamoto, K.M. et al., “Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation”, Proceedings of the National Academy of Sciences, (2001); 98(15):8554-8559. [cited by applicant]
Toure, M. et al., “Small-molecule PROTACS: new approaches to protein degradation”, Angewandte Chemie International Edition (2016); 55(6):1966-1973. [cited by applicant]
Unanue, E.R. “Perspectives on anti-CD47 antibody treatment for experimental cancer” Proceedings of the National Academy of Sciences, (Jul. 2, 2013); 110(27):10886-10887. [cited by applicant]
Van Tonder et al., “Preparation and Physicochemical Characterization of 5 Niclosamide Solvates and 1 Hemisolvate,” AAPS Pharm. Sci. Tech., (2004); 5(1):86-95. [cited by applicant]
Wang et al., “STAT3 inhibition, a novel approach to enhancing targeted therapy in human cancers (review)” Int J Onco, (Oct. 2012); 41(4):1181-1191. doi: 10.3892/ijo.2012.1568. Epub Jul. 24, 2012. [cited by applicant]
Yu et al., “The STATs of cancer—new molecular targets come of age” Nat Rev Cancer, (Feb. 2004); 4(2):97-105. doi: 10.1038/nrc1275. [cited by applicant]
Yue et al., “Targeting STAT3 in cancer: how successful are we?” Expert Opin Investig Drugs, (Jan. 2009); 18(1):45-56. doi: 10.1517/13543780802565791. [cited by applicant]
Zhou, B. et al., “Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins with Picomolar Cellular Potencies and Capable of Achieving Tumor Regression”, Journal of Medicinal Chemistry (201… [cited by applicant]
Bai et al., “A Potent and Selective Small-Molecule Degrader of STAT3 Achieves Complete Tumor Regression In Vivo.,” Cancer Cell, vol. 36, No. 5, pp. 498-511.e17 (Nov. 2019). [cited by applicant]
Chen et al., “Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors”, ACS Medicinal Chemistry Letters, vol. 1, No. 2, pp. 85-89 (Mar. 2010). [cited by applicant]
Coleman et al., “Investigation of the Binding Determinants of Phosphopeptides Targeted to the Src Homology 2 Doman of the Signal Transducer and Activator of Transcription 3. Development of a High-Affinity Peptide Inhibi… [cited by applicant]
Debnath et al., “Small Molecule Inhibitors of Signal Transducer and Activator of Transcription 3 (Stat3) Protein,” Journal of Medicinal Chemistry, vol. 55, No. 15, pp. 6645-6668 (May 2012). [cited by applicant]
Invitation to Pay Additional Fees and, Where Applicable, Protest Fee, mailed Jun. 24, 2020, for International Application No. PCT/US2020/024892 (17 total pages). [cited by applicant]
International Search Report and Written Opinion, mailed Aug. 21, 2020, for International Application No. PCT/US2020/024892 (21 total pages). [cited by applicant]
International Search Report and Written Opinion, mailed Jun. 19, 2020, for International Application No. PCT/US2020/025116 (14 total pages). [cited by applicant]
International Search Report and Written Opinion, mailed Jun. 28, 2021, for International Application No. PCT/US2021/024332 (10 total pages). [cited by applicant]
Mandal et al., “Conformationally Constrained Peptidomimetic Inhibitors of Signal Transducer and Activator of Transcription 3: Evaluation and Molecular Modeling,” J. Med. Chem., 52, 2429-2442 (2009). [cited by applicant]
Mandal et al., “Potent and Selective Phosphopeptide Mimetic Prodrugs Targeted to the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3,” Journal of Medicinal Chemistry, vol. 54, No. 10, p… [cited by applicant]
Mandal et al.,“Structure-Activity Studies of Phosphopeptidomimetic Prodrugs Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 3 (Stat3)”, International Journal of Peptide Rese… [cited by applicant]
Mandal et al., “Structure-Affinity Relationships of Glutamine Mimics Incorporated into Phosphopeptides Targeted to the SH2 Domain of Signal Transducer and Activator of Transcription 3,” J. Med. Chem., 52, 6126-6141, (20… [cited by applicant]
Mandal et al., “Synthesis of Phosphatase-Stable, Cell-Permeable Peptidomimetic Prodrugs That Target the SH2 Domain of Stat3,” Organic Letters, vol. 11, No. 15, pp. 3394-3397, (Jul. 2009). [cited by applicant]
Mandal et al., “Targeting the Src Homology 2 (SH2) Domain of Signal Transducer and Activator of Transcription 6 (STAT6) with Cell-Permeable, Phosphatase-Stable Phosphopeptide Mimics Potently Inhibits Tyr641 Phosphorylat… [cited by applicant]
Thérien et al., “Synthesis of a novel peptidic photoaffinity probe for the PTP-1B enzyme,” Bioorganic & Medicinal Chemistry Letters, vol. 14, No. 9, pp. 2319-2322 (2004). [cited by applicant]
Ren et al., “identification of a High-Affinity Phosphopeptide Inhibitor of Stat3,” Bioorganic and Medicinal Chemistry Letters, vol. 13, No. 4, pp. 633-636 (Feb. 2003). [cited by applicant]
Yao et al., “Structure-based design and synthesis of small molecule protein-tyrosine phosphatase 1B inhibitors,” Biooorganic & Medicinal Chemistry, vol. 6, No. 10, pp. 1799-1810 (Oct. 1998). [cited by applicant]
Yap et al., “Small-molecule inhibitors of dimeric transcription factors: Antagonism of protein-protein and protein-DNA interactions,” MedChemComm., vol. 3, No. 5, p. 541 (Jan. 2012). [cited by applicant]
Zhou et al., “SD-91 as A Potent and Selective STAT3 Degrader Capable of Achieving Complete and Long-Lasting Tumor Regression,” ACS Med Chem. Lett., 12, 6, 996-1004 (May 2021). [cited by applicant]
Zhou et al., “Structure-Based Discovery of SD-36 as a Potent, Selective and Efficacious PROTAC Degrader of STAT3 Protein,” Journal of Medicinal Chemstiry, vol. 62, No. 24, pp. 11280-11300 (Nov. 2019). [cited by applicant]