CDK13 Inhibitor

THZ1 is a selective and potent covalent CDK7 inhibitor with an IC₅₀ of 3.2 nM. THZ1 also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.

THZ531 is a selective and covalent inhibitor of both CDK12 and CDK13 with IC₅₀s of 158 nM and 69 nM, respectively.

SR-4835 is a potent, highly selective and ATP competitive dual inhibitor of CDK12/CDK13 (CDK12: IC₅₀=99 nM, K_d=98 nM; CDK13: K_d=4.9 nM). SR-4835 acts in synergy with DNA-damaging chemotherapy and PARP inhibitors and provokes triple-negative breast cancer (TNBC) cell death.

THZ1 Hydrochloride is a selective and potent covalent CDK7 inhibitor with an IC₅₀ of 3.2 nM. THZ1 Hydrochloride also inhibits the closely related kinases CDK12 and CDK13 and downregulates MYC expression.

CDK12-IN-9 is a potent and selective CDK12 inhibitor with an IC₅₀ of 2.2 nM. CDK12-IN-9 inhibits pSER2 (a downstream marker of CDK12/13 activity). CDK12-IN-9 can be used for the research of cancer.

MFH290 is an orally active, selective covalent CDK12/CDK13 inhibitor, with an IC₅₀ of 25 nM against human CDK12 and 49 nM against human CDK13. MFH290 reduces the phosphorylation level of CTD-RNAPII-Ser2, downregulates genes related to DNA damage response (DDR), and inhibits transcription factors regulated by super-enhancers. MFH290 can be used in research related to various cancers including leukemia.

BSJ-01-175 is a potent and selective CDK12/13 covalent inhibitor. BSJ-01-175 demonstrates exquisite selectivity, potent inhibition of RNA polymerase II phosphorylation, and downregulation of CDK12-targeted genes in cancer cells.

CDK12/13-IN-3 (Compound 12b) is the orally active inhibitor for CDK that inhibits CDK12 and CDK13 with IC₅₀ of 107.4 nM and 79.4 nM. CDK12/13-IN-3 inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression of DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative activity against multiple cancer cells with IC₅₀ of nanomolar levels. CDK12/13-IN-3 exhibits antitumor effect in mouse models, exhibits good pharmacokinetic properties with an oral bioavailability of 53.6%.

CDK6/PIM1-IN-1 is a potent and balanced dual CDK6/PIM1 inhibitor with IC₅₀ values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 inhibits CDK4 (IC₅₀=3.6 nM). CDK6/PIM1-IN-1 significantly inhibits acute myeloid leukemia (AML) cell proliferation, arrest cell cycle at the G1 phase, and promote cell apoptosis. CDK6/PIM1-IN-1 exhibits potent anti-AML activity.

CDK7-IN-28 (CDK7-1276) is a potent CDK7 inhibitor(IC₅₀＜5 nM). CDK7-IN-28 can inhibit proliferation of MDA-MB-468 cell line by blocking cell cycle and inhibiting DNA replication.

CDK12/13-IN-2 (Compound 24) is a covalent inhibitor of CDK12/13, with IC₅₀ values of 15.5 nM and 12.2 nM for CDK12 and CDK13, respectively. CDK12/13-IN-2 can inhibit the proliferation of breast cancer cells and can be used in the research of triple-negative breast cancer.

SR-5037 is an orally active CDK12 (IC₅₀ = 31 nM)/CDK13 inhibitor and CycK (DC₅₀ = 30 nM; D_max > 98%) molecular glue degrader. SR-5037 inhibits the enzymatic activity of CDK12/CycK and CDK13/CycK complexes. SR-5037 promotes the recruitment of DDB1 to the CDK12/CycK complex, thereby triggering proteasome-mediated CycK degradation. SR-5037 degrades active CycK in mouse models of triple-negative breast cancer. SR-5037 can be used in the research of cancers such as triple-negative breast cancer.

CDK-IN-9 (compound 24) is a potent CDK inhibitor, also as a molecular glue inducing an interaction between CDK12 and DDB1, with an IC₅₀ values of 4 nM for CDK2/E. CDK-IN-9 leads to polyubiquitination of cyclin K and its subsequent degradation. CDK-IN-9 induce apoptosis through dephosphorylation of retinoblastoma protein and RNA polymerase II.

YJZ5118 is a selective CDK12/CDK13 inhibitor with IC₅₀ values of 39.5 nM and 26.4 nM. YJZ5118 suppresses transcription of DNA damage response genes and induces DNA damage in tumor cells. YJZ5118 inhibits proliferation and triggers apoptosis. YJZ5118 inhibits RNA polymerase II Ser2 phosphorylation and increases Akt pathway activity. YJZ5118 exhibits synergistic effects with Akt inhibitors. YJZ5118 can be used for the research of cancer, such as prostate cancer.

Hsp90-IN-42 is a heat shock protein 90 (Hsp90) inhibitor with an IC₅₀ of 15.65 nM against human targets. Hsp90-IN-42 destabilizes EGFR and inhibits the activation of the EGFR-Akt signaling pathway. Hsp90-IN-42 suppresses the proliferation and migration of cancer cells, induces cell cycle arrest by downregulating CDK12 and CDK13, and triggers mild apoptosis via downregulating Bcl-2 and upregulating Bax. Hsp90-IN-42 inhibits tumor growth in xenograft mouse models. Hsp90-IN-42 can be used in research related to colorectal cancer.