CDK4 Inhibitor

CDK4/6-IN-2 is a potent CDK4 and CDK6 inhibitor extracted from patent US20180000819A1, Compound 1, has IC₅₀s of 2.7 and 16 nM for CDK4 and CDK6, respectively.

Damulin B is a dammarane-type saponin found in Gynostemma pentaphyllum. Damulin B can inhibit cancer cell apoptosis, decrease mitochondrial membrane potential, inhibit ROS production and cause G0/G1 phase arrest. Damulin B can prevent Cisplatin (HY-17394)-induced acute kidney injury and induce hair growth. Damulin B shows anti-inflammation anti-diabetic and anti-obesity effect. Damulin B can be used for the researches of cancer, inflammation, metabolic disease, such as lung cancer, osteoarthritis and diabetes.

PNU-292137 is an orally active, potent CDK2 inhibitor with IC₅₀s of 37 nM and 92 nM for CDK2/cyclin A and CDK2/cyclin E, respectively. PNU-292137 makes interactions with the hydrophobic pocket at the back of the CDK2 ATP pocket. PNU-292137 efficiently inhibits tumor cell proliferation in human colon and prostate tumor cell lines. PNU-292137 exhibits antitumor activity (TGI>50%) in a mouse xenograft model.

CDK9-IN-7 (compound 21e) is a selective, highly potent, and orally active CDK9/cyclin T inhibitor (IC₅₀=11 nM), which exhibits more potent over other CDKs (CDK4/cyclinD=148 nM; CDK6/cyclinD=145 nM). CDK9-IN-7 shows antitumor activity without obvious toxicity. CDK9-IN-7 induces NSCLC cell apoptosis, arrests the cell cycle in the G2 phase, and suppresses the stemness properties of NSCLC.

CAN508 is a potent, ATP-competitive CDK9/cyclin T1 inhibitor with an IC₅₀ of 0.35 μM. CAN508 exhibits a 38-fold selectivity for CDK9/cyclin T over other CDK/cyclin complexes. Antitumor activity.

Inixaciclib (NUV-422) is a blood-brain barrier-penetrant inhibitor of CDK2, CDK4 and CDK6. Inixaciclib inhibits cancer cell growth. Inixaciclib induces anti-tumor activity in xenograft models of glioblastoma, CDK4/CDK6 inhibitor-resistant HR⁺ HER2^- metastatic breast cancer, and anti-androgen-resistant prostate cancer. Inixaciclib can be used for the research of relapsed or metastatic castration-resistant prostate cancer.

NSC 625987 is a specific and high-affinity CDK4 inhibitor with an IC₅₀ of 0.2 μM for CDK4:cyclin D1. NSC 625987 shows >500-fold selectivity for CDK4 over CDK2.

SHR5428 is a potent, orally active, selective and noncovalent inhibitor of CDK7 with highly potent CDK7 enzymatic activity (IC₅₀=2.3 nM). SHR5428 inhibits triple negative breast cancer cellular activity on MDA-MB-468 cell (IC₅₀=6.6 nM).

AG-012986 is a pan-CDK inhibitor with K_i values of 44 nM (CDK1), 9.2 nM (CDK4), 94 nM (CDK2), and IC50 values of 22 nM (CDK5), 4 nM (CDK9). AG-012986 causes apoptosis of T-cells by targeting upstream kinases in the p38 Mitogen-activated protein kinase (MAPK) pathway and impairing cellular survival. AG-012986 induces cell cycle arrest, retinoblastoma protein hypophosphorylation, and reduces K_i-67 expression. AG-012986 exerts antiproliferative activity in tumor cells, demonstrates antitumor efficacy in human xenograft models, and causes retinal and peripheral neurotoxicity, plus immune cell toxicity. AG-012986 can be used for the research of colon carcinoma, non-small cell lung carcinoma, lung carcinoma, breast carcinoma, ovarian tumor, pancreatic carcinoma, osteosarcoma, lymphoma, leukemia, retinotoxicity.

GP-82996 (CINK4) is a pharmacological inhibitor of CDK4/6. GP-82996 has IC₅₀s of 1.5, 5.6 and 25 μM for CDK4/cyclin D1, CDK6/cyclin D1 and Cdk5/p35, respectively. GP-82996 induces the apoptosis of cancer cells U2OS. GP-82996 can be used in the research of cancer.

Ganoderic acid H is a hydroxylated lanostane-type triterpenoid derived from Ganoderma lucidum with anticancer activity. Ganoderic acid H inhibits the constitutive transactivation activity of AP-1 and NF-κB; it also downregulates the secretion of uPA and the expression of CDK4, and suppresses the growth, adhesion, migration and invasion of cancer cells. Ganoderic acid H inhibits HIV-1 protease in vitro. Ganoderic acid H can be used in studies related to breast cancer and HIV infection.

Abemaciclib metabolite M20-d₈ is the deuterium labeled Abemaciclib metabolite M20. Abemaciclib metabolite M20 (LSN3106726), the active metabolite of Abemaciclib, is a selective CDK4/6 inhibitor.

ON-013100, an antineoplastic agent, acts a mitotic inhibitor that could inhibit Cyclin D1 expression.

AT7519 (AT7519M) TFA 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.

CDK4/6-IN-12 is a potent cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. CDK4/6-IN-12 has enzymatic inhibitory activity for CDK4 and CDK6 with IC₅₀ of 592.3 nM and 3090 nM, respectively. CDK4/6-IN-12 can be used for the research of cancer.

Fascaplysin is an antimicrobial and cytotoxic red pigment, that can come from the marine sponge (Fascaplysinopsis sp.). Fascaplysin has been synthesized in seven steps from indole (65% yield). Fascaplysin can induces apoptosis and autophagy in human leukemia HL-60 cells. Fascaplysin shows anti-tumor activity.

CDK4/6-IN-9 (compound 10) is a selective CDK4/6 inhibitor with an IC₅₀ of 905 nM for CDK6/cyclin D1. CDK4/6-IN-9 has the potential for multiple myeloma (MM) research.

CDK6/PIM1-IN-1 (Compound 51) hydrochloride is an orally active and potent dual CDK6/PIM1 inhibitor with IC₅₀ values of 39 and 88 nM, respectively. CDK6/PIM1-IN-1 hydrochloride inhibits CDK4 (IC₅₀=3.6 nM). CDK6/PIM1-IN-1 hydrochloride 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.

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.

ZDLD20, a β-carboline, is orally active and selective CDK4/CycD3 inhibitor with an IC₅₀ value of 6.51  μM. ZDLD20 exhibits potent anti-HCT116 activity including inhibition of colony formation, inhibition of invasion and migration, inducing of apoptosis, and arresting of G1 phase in cell cycle. ZDLD20 exhibits potent anticancer activity.