Granted Patent
B2
US 12,514,859 · App. 18/432,931 · Granted Jan 6, 2026
Pyrazole pyrimidine derivative and uses thereof
Inventors:
Yinon Ben Neriah (Mevasseret Zion, IL); Guy Brachya (Jerusalem, IL); Ido Burstain (Moshav Sde-Yaakov, IL); Waleed Minzel (Kafr-Kanna, IL); Int Snir-Alkalay (Mevasseret Zion, IL); Joseph P. Vacca (Telford, PA); Dansu Li (Warrington, PA)
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Abstract
The present invention provides pyrazole pyrimidine derivatives which inhibit Casein kinase I (CKI) and/or Interleukin-1 receptor-associated kinase 1 (IRAKI) and methods of their manufacture, compositions comprising them and uses thereof in methods of treating malignant disease and disorders and methods for treating inflammatory diseases and disorders.
Claims (6)
1 . A compound having the formula:
or a pharmaceutically acceptable salt thereof.
2 . A compound having the formula:
or a pharmaceutically acceptable salt thereof.
3 . A compound having the formula:
or a pharmaceutically acceptable salt thereof.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Dec 8, 2025
From: BEN NERIAH, YINON; BRACHYA, GUY; BURSTAIN, IDO; MINZEL, WALEED; SNIR-ALKALAY, IRIT; VACCA, JOSEPH; LI, DANSU
To: YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD.
Reel/Frame 073141/0490 →
Continuity (6)
Continuation
15748536
Provisional Application
62268750
· Dec 17, 2015
Provisional Application
62200846
· Aug 4, 2015
References Cited (39)
US 6884804B2
· Choon-Moon
· 2005
[cited by applicant]
US 20090036448A1
· Sekiguchi et al.
· 2009
[cited by applicant]
US 20200383984A1
· Snir-Alkalay et al.
· 2020
[cited by applicant]
JP 2007145819A
· 2007
[cited by applicant]
WO 2002092573A2
· 2002
[cited by applicant]
WO 2005095357A2
· 2005
[cited by applicant]
WO 2007129195A2
· 2007
[cited by applicant]
WO 2007138277A1
· 2007
[cited by applicant]
WO 2009071701A1
· 2009
[cited by applicant]
WO 2013066684A1
· 2013
[cited by applicant]
WO 2015048281A1
· 2015
[cited by applicant]
WO WO2015058140A1
· 2015
[cited by examiner]
Adams et al., “IRAK1 is a novel DEK transcriptional target and is essential for head and neck cancer cell survival,” Oncotarget. 2015, 6, 43395-407.
[cited by applicant]
Amit et al., “Axin-mediated CKI phosphorylation of β-catenin at Ser 45: a molecular switch for the Wnt pathway,” Genes Dev. 2002, 16:1066-76.
[cited by applicant]
Aran et al., “Widespread parainflammation in human cancer,” Genome Biol. 2016, 17, 145.
[cited by applicant]
Bahia et al., “Interleukin-1 receptor associated kinase inhibitors: Potential therapeutic agents for inflammatory- and immune-related disorders,” Cell. Signal. 2015, 27, 1039-55.
[cited by applicant]
Berge et al., “Pharmaceutical salts,” J. Pharm. Sci. 1977, 66, 1-19.
[cited by applicant]
Cheong and Virshup, “Casein kinase 1: Complexity in the family,” J. Biochem. Cell Biol. 2011, 43, 465-9.
[cited by applicant]
Clevers and Nusse, “Wnt/β-catenin signaling and disease,” Cell 2012, 149, 1192-205.
[cited by applicant]
Duan et al., “mTOR generates an auto-amplification loop by triggering the βTrCP- and CK1α-dependent degradation of DEPTOR,” Mol. Cell 2011, 44, 317-24.
[cited by applicant]
Elyada et al., “CK1α ablation highlights a critical role for p53 in invasiveness control,” Nature 2011, 470, 409-13.
[cited by applicant]
Fabian et al., “A small molecule-kinase interaction map for clinical kinase inhibitors,” Nat. Biotechnol. 2005, 23, 329-36.
[cited by applicant]
Fish et al., “Isolation and characterization of human casein kinase I epsilon (CKI), a novel member of the CKI gene family,” J. Biol. Chem. 1995, 270, 14875-83.
[cited by applicant]
Karaman et al., “A quantitative analysis of kinase inhibitor selectivity,” Nat. Biotechnol. 2008, 26, 127-32.
[cited by applicant]
Knippschild et al., “The casein kinase 1 family: participation in multiple cellular processes in eukaryotes,” Cell. Signal. 2005, 17, 675-89.
[cited by applicant]
Lasry and Ben-Neriah, “Senescence-associated inflammatory responses: aging and cancer perspectives,” Trends Immunol. 2015, 36, 217-28.
[cited by applicant]
Minzel et al., “Small molecules co-targeting CKIα and the transcriptional kinases CDK7/9 control AML in preclinical models,” Cell 2018, 175, 171-85.
[cited by applicant]
Pribluda et al., “A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism,” Cancer Cell 2013, 24, 424-56.
[cited by applicant]
Rhyasen et al., “Differential IRAK signaling in hematologic malignancies,” Exp. Hematol. 2013, 41, 1005-7.
[cited by applicant]
Rhyasen et al., “Targeting IRAK1 as a therapeutic approach for myelodysplastic syndrome,” Cancer Cell 2013, 24, 90-104.
[cited by applicant]
Sansom et al., “Loss of Apc in vivo immediately perturbs Wnt signaling, differentiation, and migration,” Genes Dev. 2004, 18, 1385-90.
[cited by applicant]
Schittek and Sinnberg, “Biological functions of casein kinase 1 isoforms and putative roles in tumorigenesis,” Mol. Cancer 2014, 13, Article 231.
[cited by applicant]
Wee et al., “IRAK1 is a therapeutic target that drives breast cancer metastasis and resistance to paclitaxel,” Nat. Commun. 2015, 6, 8746.
[cited by applicant]
Zemp et al., “CK1δ and CK1ε are components of human 40S subunit precursors required for cytoplasmic 40S maturation,” J. Cell Sci. 2014, 127, 1242-53.
[cited by applicant]