CDK7 Inhibitor

Abemaciclib (LY2835219) is a selective and BBB-permeable CDK4/6 inhibitor with IC₅₀ values of 2 nM and 10 nM for CDK4 and CDK6, respectively.

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.

Abemaciclib methanesulfonate (LY2835219 methanesulfonate) is a selective and BBB-permeable CDK4/6 inhibitor with IC₅₀s of 2 nM and 10 nM for CDK4 and CDK6, respectively.

SNS-032 (BMS-387032) is a potent and selective inhibitor of CDK2, CDK7, and CDK9 with IC₅₀s of 38 nM, 62 nM and 4 nM, respectively. SNS-032 has antitumor effect.

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

Q901 (CDK7-IN-21) TFA is a selective and potent CDK7 inhibitor with an IC₅₀ of 10 nM. Q901 TFA disrupts MYC and E2FTOP1-DPCs and sensitizes tumor to TOP1 inhibitors by suppressing RNAPII transition from initiation to elongation. Q901 TFA can inhibit tumor growth and significantly enhances tumor growth inhibition combined with TOP1 inhibitors. Q901 TFA can be used for the research of cancer, such as colon cancer and lung cancer.

(S)-JNJ-3738 is a CDK7 inhibitor. (S)-JNJ-3738 regulates kinase activity and exerts weak inhibitory effects on the activity of mutant CDK7. (S)-JNJ-3738 is applicable for cancer research.

JAK1/CDK7-IN-1 is a JAK1/CDK7 inhibitor. JAK1/CDK7-IN-1 forms a stable and tightly bound complex with JAK1. JAK1/CDK7-IN-1 disrupts the cell cycle, induces G₂/M phase arrest, and increases the proportion of pre-G₁ phase cells. JAK1/CDK7-IN-1 induces cellular apoptosis (apoptosis) and necrosis. JAK1/CDK7-IN-1 is applicable to research related to breast cancer and prostate cancer.

SY-5609 (CDK7-IN-3) is an orally active, highly selective, noncovalent CDK7 inhibitor with a K_D of 0.065 nM. SY-5609 shows poor inhibition on CDK2 (K_i=2600 nM), CDK9 (K_i=960 nM), CDK12 (K_i=870 nM). SY-5609 induces apoptosis in tumor cells and has antitumor activity.

Samuraciclib hydrochloride (CT7001 hydrochloride) is a potent, selective, ATP-competitive and orally active CDK7 inhibitor, with an IC₅₀ of 41 nM. Samuraciclib hydrochloride displays 45-, 15-, 230- and 30-fold selectivity over CDK1, CDK2 (IC₅₀ of 578 nM), CDK5 and CDK9, respectively. Samuraciclib hydrochloride inhibits the growth of breast cancer cell lines with GI₅₀ values between 0.2-0.3 µM. Samuraciclib hydrochloride has anti-tumor effects.

Toyocamycin (Vengicide) is an adenosine analog produced by Streptomyces diastatochromogenes, acts as an XBP1 inhibitor. Toyocamycin blocks RNA synthesis and ribosome function, and induces apoptosis. Toyocamycin affects IRE1α-XBP1 pathway, and inhibits XBP1 mRNA cleavage with an IC₅₀ value of 80 nM with affecting IRE1α auto-phosphorylation. Toyocamycin specifically inhibits CDK9 with an IC₅₀ value of 79 nM.

YKL-5-124 is a potent, selective, irreversible and covalent CDK7 inhibitor with IC₅₀s of 53.5 nM and 9.7 nM for CDK7 and CDK7/Mat1/CycH, respectively. YKL-5-124 is >100-fold greater selective for CDK7 than CDK9 and CDK2, and inactive against CDK12 and CDK13. YKL-5-124 induces a strong cell-cycle arrest, inhibits E2F-driven gene expression, and exhibits little effect on RNA polymerase II phosphorylation status.

Tambiciclib (GFH009, JSH-009) is an orally active, highly potent and selective CDK9 inhibitor (IC₅₀ = 1 nM), demonstrating >200-fold selectivity over other CDKs, >100-fold selectivity over DYRK1A/B, and excellent selectivity over 468 kinases/mutants. Tambiciclib demonstrates potent in vitro and in vivo antileukemic efficacy in acute myeloid leukemia (AML) mouse models by inhibiting RNA Pol II phosphorylation, downregulating MCL1 and MYC, and inducing apoptosis. Tambiciclib can be used for AML research.

AT7519 (AT7519M) as a potent inhibitor of CDKs, with IC₅₀s of 210, 47, 100, 13, 170, and <10 nM for CDK1, CDK2, CDK4 to CDK6, and CDK9, respectively.

AZD-5438 is a potent CDK1, CDK2, and CDK9 inhibitor, with IC₅₀s of 16 nM, 6 nM, and 20 nM in cell-free assays, respectively. AZD-5438 shows less inhibition activity against GSK3β, CDK5 and CDK6 .

BTX-A51 (Casein Kinase inhibitor A51) is a potent and orally active casein kinase 1α (CK1α) inhibitor. BTX-A51 induces leukemia cell apoptosis, and has potent anti-leukemic activities.

(R)-CR8, a second-generation analog of Roscovitine, is a potent CDK1/2/5/7/9 inhibitor. (R)-CR8 inhibits CDK1/cyclin B (IC₅₀=0.09 μM), CDK2/cyclin A (0.072 μM), CDK2/cyclin E (0.041 μM), CDK5/p25 (0.11 μM), CDK7/cyclin H (1.1 μM), CDK9/cyclin T (0.18 μM) and CK1δ/ε (0.4 μM). (R)-CR8 induces apoptosis and has neuroprotective effect. (R)-CR8 acts as a molecular glue degrader that depletes cyclin K.

Mevociclib (SY-1365) is a potent and first-in-class selective CDK7 inhibitor, with a K_i of 17.4 nM. Mevociclib exhibits anti-proliferative and apoptotic effects in solid tumor cell lines. Mevociclib possesses anti-tumor activity in hematological and multiple aggressive solid tumors.

KB-0742 is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 has potent anti-tumor activity.

KB-0742 dihydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 dihydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 dihydrochloride has potent anti-tumor activity.