CDK7 Inhibitor

Tambiciclib (GFH009, JSH-009) dimaleate 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 dimaleate 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 dimaleate can be used for AML research.

LDC3140 is a selective CDK7 inhibitor (IC₅₀<5 nM). By inhibiting the activity of CDK7, LDC3140 affects the regulation of the cell cycle, leading to cell cycle arrest and thus inhibiting the proliferation of tumor cells. LDC3140 can be used in the research of cancer treatment.

BS-181 is a potent and selective CDK7 inhibitor (IC₅₀=21 nM) than Seliciclib (HY-30237). BS-181 is also against CDK2, CDK5 and CDK9 with IC₅₀ values of 880, 3000 and 4200 nM, respectively (fails to block CDK1, 4 and 6). BS-181 inhibits a panel of cancer cells growth (IC₅₀=11.5 μM-37.3 μM) and induces cell apoptosis. BS-181 has the potential for the research of cancer therapy.

THZ1-R is a non-cysteine reactive analog of THZ1 which displays diminished activity for CDK7 inhibition. THZ1-R binds to CDK7 with a K_d of 142 nM.

CDK7-IN-1, an analog of YKL-5-124, is a cyclin-dependent kinase 7 (cdk7) inhibitor, with an IC₅₀ of less than 100 nM, extracted from patent WO 2016105528 A2, Compound 215.

IV-361 is an orally active and selective CDK7 inhibitor (K_i≤50 nM). IV-361 has anti-cancer activity (US20190256531A1).

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.

(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.

Olomoucine II is a potent CDK inhibitor with IC₅₀ values of 0.06, 0.1, 0.45, 7.6, 19.8 µM for CDK9/cyclin T, CDK2/cyclin E, CDK7/cyclin H, CDK1/cyclin B, CDK4/cyclin D1, respectively. Olomoucine II shows antiproliferative activity.

CDK7-IN-2 hydrochloride hydrate (Example 6) is a potent and selective CDK7 inhibitor. CDK7-IN-2 has potent anti-cancer activity.

BS-181 dihydrochloride is a potent and selective CDK7 inhibitor (IC₅₀=21 nM) than Seliciclib (HY-30237). BS-181 is also against CDK2, CDK5 and CDK9 with IC₅₀ values of 880 nM, 3000 nM and 4200 nM, respectively (fails to block CDK1, 4 and 6). BS-181 dihydrochloride inhibits a panel of cancer cells growth (IC₅₀=11.5 μM-37.3 μM) and induces cell apoptosis. BS-181 dihydrochloride has the potential for the research of cancer therapy.

CDK7-IN-11 is an orally active CDK7 inhibitor. CDK7-IN-11 exhibits high CDK7 inhibitory activity with IC₅₀ value of 4.2 nM. CDK7-IN-11 can be effectively used for the research of diseases associated with CDK7.

CDK7-IN-30 (Compound 22) is a CDK7 inhibitor (IC₅₀ = 7.21 nM) that effectively inhibits the phosphorylation of RNA Polymerase II and CDK2. CDK7-IN-30 CDK7-IN-30 can induce cell apoptosis and has anti-cancer activity and can be used in cancer research.

CDK7-IN-6 is a potent and selective cyclin-dependent kinase (CDK7) inhibitor (IC₅₀≤100 nM), extracted from patent WO2019197549 A1, compound 210. CDK7-IN-6 is > 200-fold selective for CDK7 over CDK1, CDK2, and CDK5. CDK7-IN-6 can be used for the research of cancer.

CDK7-IN-16 (compound 9) is a potent CDK 7 inhibitor with an IC₅₀ range of 1 ~ 10 nM. CDK7-IN-16 can be used for researching anticancer, especially the cancer with transcriptional dysregulation.

CDK7-IN-10 is a CDK7 inhibitor with an IC₅₀ of less than 100 nM, extracted from patent WO2021016388A1, compound I-1. CDK7-IN-10 is useful in inhibiting the activity of a kinase. CDK7-IN-10 has the potential of inhibiting cell growth and inducing cell apoptosis.

HDAC1/CDK7-IN-1 (compound 8e) is a dual CDK7 and HDAC1 inhibitor with IC₅₀s of 893 nM and 248 nM, respectively. HDAC1/CDK7-IN-1 inhibits the growth cells of MDA-MB-231, MCF-7, A549, and HCT-116 cancer cells. HDAC1/CDK7-IN-1 induces cell cycle arrest and apoptosis in HCT-116 cells, as well as hindered the migration of HCT-116 cells.

CDKI-83 is a potent CDK9 and CDK1 inhibitor with K_i values of 21 nM and 72 nM for CDK9/T1 and CDK1/B, respectively. CDKI-83 demonstrates effective anti-proliferative activity in human tumour cell lines with a GI₅₀<1 μM. CDKI-83 effectively induces apoptosis in A2780 human ovarian cancer cells. CDKI-83 reduces phosphorylation at Ser-2 of RNA polymerase II (RNAPII) by inhibiting cellular CDK9 activity, and down-regulates Mcl-1 and Bcl-2. CDKI-83 has the potential for anti-cancer research.

CDK7-IN-32 (compound10) is a CDK7 inhibitor.