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-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.

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 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-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%.

PARP1/CDK12-IN-1 (107) is a dual inhibitor that targets both CDK12 and PARP1, exhibiting IC50 values of 285 nM and 34 nM, respectively.

CDK12-IN-8 (Compound Cpd143) is an orally active, highly selective inhibitor of cyclin-dependent kinase 12 (CDK12). It blocks the phosphorylation of serine 2 in the C-terminal domain (CTD) of RNA polymerase II, thereby interfering with gene transcription elongation and DNA damage repair pathways. CDK12-IN-8 holds potential for research in cancers with high CDK12 expression, such as small cell lung cancer and triple-negative breast cancer.

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-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).

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).

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.

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

CDK12-IN-7 (Compound 2), a dual inhibitor of CDK12 and CDK2, exhibits IC 50 values of 42 nM and 196 nM, respectively. This compound demonstrates anti-cell proliferation properties, making it applicable in cancer research.

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.

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

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).

ZSQ836 is a dual covalent inhibitor of CDK12 CDK13 with oral bioactivity, displaying an EC50 value of 32 nM against CDK12. This compound can induce cell apoptosis (apoptosis) and demonstrates in vivo anticancer properties. ZSQ836 is applicable for research in ovarian cancer.

YJ1206 is a highly potent and selective CDK12 13 PROTAC degrader (IC50 =12.55 nM) with the advantages of oral administration and low toxicity, which triggers gene-length-dependent transcription elongation defects, leading to DNA damage and cell-cycle arrest, and inhibits the proliferation of a subpopulation of prostate cancer cells. YJ1206 can synergize with AKT pathway inhibitors to effectively inhibit prostate cancer.

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

YJ9069 is a selective CDK12 CDK13P ROTAC degrader with an IC50 of 22.22 nM in VCaP cells. Rapid degradation of CDK12 13 by this compound triggers transcription elongation defects dependent on gene length, leading to DNA damage and cell cycle arrest. YJ9069 effectively inhibits the proliferation of prostate cancer cell subpopulations and significantly suppresses prostate tumor growth in vivo.

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.