cdk13

THZ531 is a covalent inhibitor of both CDK12(IC50=158 nM) and CDK13(IC50=69 nM).

SR-4835 is a highly selective dual inhibitor of CDK12 and CDK13(CDK12: IC50=99 nM, Kd=98 nM; CDK13: Kd=4.9 nM), which disables triple-negative breast cancer (TNBC) cells

CDK12 13-IN-2 (Compound 24) is a covalent inhibitor of CDK12 and CDK13, exhibiting IC50 values of 15.5 nM and 12.2 nM, respectively. It effectively inhibits the proliferation of breast cancer cells and can be utilized in the research of triple-negative breast cancer.

YJZ5118 is a CDK12/13 inhibitor, possessing IC50 values of 39.5 nM and 26.4 nM for CDK12 and CDK13, respectively. This compound can inhibit tumor cell proliferation by inducing DNA damage and apoptosis (Apoptosis) and exhibits a synergistic effect with Akt inhibitors. YJZ5118 is applicable in cancer research.

CDK12/13-IN-3 (Compound 12b) is an orally active CDK inhibitor targeting CDK12 and CDK13, with IC50 values of 107.4 nM and 79.4 nM, respectively. This compound inhibits the phosphorylation of Ser2 on the CTD of RNA polymerase II, induces DNA damage, and downregulates the gene expression involved in the DNA damage response (DDR). CDK12/13-IN-3 exhibits antiproliferative effects against various cancer cells with nanomolar IC50 values. In mouse models, it demonstrates antitumor activity, favorable pharmacokinetic properties, and an oral bioavailability of 53.6%.

CDK-IN-9 (compound 24) is a potent inhibitor of CDK and acts on CDK2/E (IC50: 4 nM). It functions as a molecular gel that induces interaction between CDK12 and DDB1, and can dephosphorylate retinoblastoma protein and RNA polymerase II, thereby inducing apoptosis.

CDK6/PIM1-IN-1 is a balanced, potent dual inhibitor of CDK6 (IC50: 39 nM) and PIM1 (IC50: 88 nM), also showing inhibitory activity on CDK4 (IC50: 3.6 nM). It significantly inhibits the proliferation of acute myeloid leukemia (AML) cells, arrests the cell cycle in G1 phase, induces cell apoptosis, and demonstrates anti-AML activity.

PROTAC CDK12 13 Degrader-1 (7f) is a potent and selective dual degrader of the cell cycle protein-dependent kinases CDK12 (DC50: 2.2 nM) and CDK13 (DC50: 2.1 nM), used in the context of breast cancer.

THZ1 Hydrochloride is a potent, selective covalent inhibitor of CDK7, exhibiting an IC50 value of 3.2 nM. It also targets closely related kinases CDK12 and CDK13, leading to the downregulation of MYC expression.

YKL-5-124 TFA, a potent and selective irreversible covalent inhibitor of CDK7, demonstrates IC50 values of 53.5 nM for CDK7 and 9.7 nM for the CDK7 Mat1 CycH complex. It exhibits over 100-fold selectivity for CDK7 over CDK9 and CDK2, while showing no activity against CDK12 and CDK13. This compound effectively induces cell-cycle arrest, inhibits E2F-driven gene expression, and has minimal impact on the phosphorylation status of RNA polymerase II.

CDK HDAC-IN-3 is an orally active dual inhibitor of HDACs and CDKs, offering potent and selective inhibition of CDK9, CDK12, CDK13, HDAC1, HDAC2, and HDAC3, with IC50 values of 98.32 nM, 98.85 nM, 100 nM, 62.12 nM, 93.28 nM, and 82.87 nM, respectively, and is applicable in the treatment of acute myeloid leukemia (AML) [1].

FMF-06-098-1 is a multitargeted depressant that promotes the degradation of various kinases including AAK1, ABL2, AURKA, AURKB, BUB1B, CDC7, CDK1, CDK12, CDK13, CDK2, CDK4, CDK6, CDK7, CDK9, CHEK1, CSNK1D, EPHA1, PAK, FGFR1, GAK, IRAK4, ITK, LIMK2, MAP4K2, MAP4K3, MAPK6, MAPK7, MARK4, MELK, PKN3, PLK4, PRKAA1, PTK2, PTK6, RPS6KA4, SGK2, STK35, TNK2, UHMK1, ULK1, and WEE1 [1].