cdk12

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

CDK12-IN-3 is a selective and potent CDK12 inhibitor with anti-tumor activity, which can be used to study malignant tumors.

CDK12-IN-6, a pyrazolotriazine compound, is a powerful inhibitor of CDK12. Its inhibitory activity is significant with an IC50 value of 1.19 μM when tested at high ATP concentration (2 mM). Notably, CDK12-IN-6 does not exhibit any inhibitory effect on CDK2 Cyclin E (IC50 >20 μM) and CDK9 Cyclin T1 (IC50 >20 μM) when tested under the same high ATP conditions (2 mM) (WO2021116178A1).

CDK12-IN-5 is a potent CDK12 inhibitor with potential anticancer and antitumor activity, and can be used orally in the study of breast and ovarian cancer.

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.

CDK12 13-IN-1 (Compound 4) serves as an inhibitor of CDK12 13 and exhibits antitumor activity [1].

CDK12-IN-2 (CDK12 inhibitor 2) is an effective and selective inhibitor of CDK12 with an IC50 of 52 nM, >100 μM, >10 μM and 16 μM for CDK12, CDK2, CDK7, and CDK9. CDK12-IN-2 can be used in studies about the function of CDK12.

CDK12-IN-E9 is a cell cycle protein kinase (CDK) inhibitor with anticancer and antitumor activity that can be used in the study of breast cancer.

CDK12-IN-4, a pyrazolotriazine compound, exhibits potent inhibition of CDK12 by achieving an IC50 value of 0.641 μM, utilizing high ATP levels (2 mM). Notably, CDK12-IN-4 does not impact CDK2 Cyclin E (IC50 > 20 μM) or CDK9 Cyclin T1 (IC50 > 20 μM) under the influence of high ATP (2 mM) levels (WO2021116178A1).

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.

ALK-IN-29 (compound 4c) exhibits notable inhibitory activity against tyrosine kinases such as ALK, CDK2 CyclinE1, and FAK, with the strongest inhibition observed against ALK kinase, showing a 40.63% inhibition rate at a concentration of 10 μM. ALK-IN-29 is useful for cancer research.

SY-5609 (CDK7-IN-3) is a selective non-covalent CDK7 inhibitor (Kd value is 0.07 nM), with weak inhibitory activity against CDK2, CDK9 and CDK12 with IC50 values ​​of 5.5, 1.9 and 1.7 μM, respectively, and has anti-tumor activity and inhibits cell apoptosis.

dCeMM3 (2-(1H-benzimidazol-2-ylsulfanyl)-N-(5-chloropyridin-2-yl)acetamide) is a glue degrader. dCeMM3 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, result in inducing ubiquitination and degradation of cyclin K.

BSJ-4-116 is a highly potent and selective CDK12 degrader (PROTAC) with an IC50 of 6 nM. It downregulates DDR genes through a premature termination of transcription, primarily through increasing poly(adenylation).

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

dCeMM2 is a glue degrader. dCeMM2 prompts an interaction of CDK12-cyclin K with a CRL4B ligase complex, leading to the ubiquitination and degradation of cyclin K.

BSJ-5-63 is an effective degrader of CDK12, CDK7, and CDK9. It reduces the protein expression of CDK12, CDK7, CDK9, RNAPII, and Cyclin K, and also decreases the mRNA expression of BRCA1 and BRCA2. BSJ-5-63 exhibits anticancer activity and holds potential for prostate cancer research.

ZLC491 is an orally active PROTAC degrader targeting CDK12 13. It is utilized in cancer research.

PARP-1 2-IN-2-IN-1 (Compound 12e) effectively inhibits PARP1 2 and CDK12 with IC50 values of 34 nM, 30 nM, and 285 nM respectively, impairing DNA damage repair and inducing cell cycle arrest and apoptosis. This compound also hampers the proliferation of TNBC cells and the growth of TNBC xenograft tumors [1].

MFH290 is a novel cysteine (Cys)-directed covalent inhibitor of CDK12 13. MFH290 forms a covalent bond with Cys-1039 of CDK12, exhibits excellent kinome selectivity, inhibits the phosphorylation of serine-2 in the C-terminal domain (CTD) of RNA-polymerase II (Pol II), and reduces the expression of key DNA damage repair genes. Importantly, these effects were demonstrated to be CDK12-dependent as mutation of Cys-1039 rendered the kinase refractory to MFH290 and restored Pol II CTD phosphorylation and DNA damage repair gene expression. Consistent with its effect on DNA damage repair gene expression, MFH290 augments the antiproliferative effect of the PARP inhibitor olaparib.

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].

SHR5428 is an orally active, selective, noncovalent inhibitor of CDK7, displaying potent enzymatic inhibition (IC50 = 2.3 nM) and effectively suppressing cellular activity in triple-negative breast cancer MDA-MB-468 cells (IC50 = 6.6 nM) [1].

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.