CDK9 Inhibitor

CDK6/9-IN-1 (compound 66) is an orally active active and dual CDK 6 and CDK 9 inhibitor, with IC₅₀ values of 40.5 nM and 39.5 nM for CDK6 anmd CDK9, respectively.

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.

A-1592668 is a selective CDK9 inhibitor. A-1592668 induces Apoptosis. A-1592668 plus Venetoclax (HY-15531) co-treatment inhibits the growth of Jeko-1 tumors.

CDK4/9-IN-1 (Compound 29) is a selective dual CDK4/9 inhibitor with IC₅₀ values of 23 nM and 12 nM, respectively. CDK4/9-IN-1 is promising for research of cancers.

CDK9-IN-51 is a CDK9 inhibitor. CDK9-IN-51 binds stably to purified CDK9 protein via interactions with key active-site residues Cys106, Asp109, and Phe103. CDK9-IN-51 exhibits antiproliferative activity against multiple cancer cells. CDK9-IN-51 can be used for the research of cancer, such as lung carcinoma, cervical carcinoma and breast carcinoma.

CDK2-IN-12 (compound 10b) is a potent CDK2 inhibitor, with an IC₅₀ of 11.6 μM. CDK2-IN-12 inhibits hCA (carbonic anhydrase) isoforms I, II, IX and XII, with K_I values of 3534, 638.4, 44.3, and 48.8 nM. CDK2-IN-12 shows anticancer activity.

CDK9-IN-45 (Compound B11) is a highly selective CDK9 inhibitor with IC₅₀ values for CDK9 and CDK1 of 7.13 and 489.5 nM respectively. CDK9-IN-45 exhibits a potent inhibitory effect on colorectal cancer cells. CDK9-IN-45 induces cell apoptosis and leads to significant accumulation of ROS. CDK9-IN-45 activates Caspase-3, downregulates Mcl-1, XIAP, and c-Myc. CDK9-IN-45 can be used for research on colorectal cancer.

ZLMT-72 is an orally active dual CDK2 and CDK9 inhibitor with IC₅₀s of 0.741 nM and 1.03 nM, respectively. ZLMT-72 shows good selectivity in kinase profiling andcholinesterase inhibition activity. ZLMT-72 has strong antiproliferative effects in the colorectal cancer (CRC) cell line HCT116 (GI₅₀ < 0.1 nM). ZLMT-72 induces apoptosis by inhibiting thephosphorylation of retinoblastoma and RNA polymerase II, resulting in downregulation of antiapoptotic proteins (Mcl-1 and XIAP). ZLMT-72 can be used for the study of colorectal cancer (CRC).

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.

LCI133 is afirst-in-class,nanomolar-potent, selective multikinase inhibitor targeting CDK4/6/9 and AURKA/B (IC₅₀ = 4.7/10.2/4.1 nM and 2.8/10.6 nM). LCI133 induces S/G2 cell-cycle arrest and robust apoptosis in MYCN-amplified neuroblastoma BE(2)-C cells. LCI133 demonstrates significant antitumor efficacy in a BE(2)-C neuroblastoma xenograft model.

CDK9-IN-49 is a CDK9 inhibitor with an IC₅₀ of 7.32 nM. CDK9-IN-49 inhibits the proliferation of various cancer cells. CDK9-IN-49 can be used in the research of cancers such as acute myeloid leukemia and prostate cancer.

CDK9-IN-37 (Compound 24) is a CDK9 inhibitor (EC₅₀: 5.5 nM) with weak inhibition on other CDK isoforms, showing high selectivity. CDK9-IN-37 has significant antiproliferative activity against acute myeloid leukemia MOLM-13 cells (IC₅₀: 0.034 μM). CDK9-IN-37 inhibits the CDK9 signaling pathway, reduces the phosphorylation level of RNAP II CTD (Ser2), downregulates the anti-apoptotic protein McI-1, induces cell apoptosis, and arrests the cell cycle at the G2/M phase. CDK9-IN-37 can be used in the study of acute myeloid leukemia (AML).

CDK5-IN-4 (compound 4) is a potent multikinase type-II inhibitor targeting CDK5, with an IC₅₀ of 9.8 μM. CDK5-IN-4 also inhibits GSK-3α, GSK-3β, CDK9, and CDK2, with IC₅₀ values of 0.98, 4.00, 1.76, and 6.24 μM, respectively. CDK5-IN-4 can be used for glioblastoma research.

CDK9 ligand 1 is a CDK9-targeting ligand. CDK9 ligand 1 can be used for PROTAC synthesis, and serves as the target protein ligand for PROTAC CDK9 Degrader-1 (HY-103628).

CDK9-IN-24 (compound 21a) is a highly selective CDK9 inhibitor with significant inhibitory effect on tumor growth. CDK9-IN-24 effectively blocks cell proliferation and induces apoptosis by downregulating Mcl-1 and c-Myc, and can be used in acute myeloid leukemia research.

BAY-1112054 (BAY-958) hydrochloride is a potent PTEFb/CDK9 inhibitor with high selectivity demonstrated, particularly within the CDK family. BAY-1112054 hydrochloride shows strong antiproliferative activity against cancer cell lines such as HeLa and MOLM-13. BAY-1112054 hydrochloride exhibits good metabolic stability. BAY-1112054 hydrochloride effectively inhibits tumor growth in mouse xenograft models without significant toxicity.

Rohitukine is an orally active CDK9/T1 inhibitor with an IC₅₀ of 0.3 μM. Rohitukine blocks ATP binding sites of CDK2/A and CDK9/T1, suppresses PPARγ, AKT, mTOR, C/EBPα, SREBP-2, and NF-κB signaling, and increases hepatic LXRα expression. Rohitukine induces S-phase cell cycle arrest, ROS generation, apoptosis, and exhibits anti-inflammatory activity. Rohitukine can be used for the research of leukemia, pancreatic cancer, prostate cancer, breast cancer, CNS cancer, ovarian cancer, lung cancer, dyslipidemia, inflammatory diseases, inflammatory bowel disease, and arthritis.

SLM6 is a sangivamycin-like molecule. SLM6 is a CDK9 inhibitor. SLM6 inhibits CDK9/cyclin K and CDK9/cyclin T1 kinase activity with IC₅₀s of 280 nM and 133 nM, respectively. SLM6 also inhibits CDK1/cyclin B and CDK2/ cyclin A with IC₅₀s of less than 300 nM. SLM6 induces apoptosis in multiple myeloma (MM) cells.

CDK9-IN-34 (Compound 1b) is an inhibitor for CDK9 with an IC₅₀ of 0.25 μM. CDK9-IN-34 exhibits cytotoxicity to cancer cell HCT116, MCF7 and K652 with IC₅₀s of 1.43, 3.01 and 50.27 μM, respectively. CDK9-IN-34 exhibits antiviral activity against coronavirus 229E with an IC₅₀ of 145.92 μM.

CDK9-IN-33 (compound C35) is a potent, selective and orally active CDK9 inhibitor with IC₅₀ values of 17.44, 160, 316.30, 1771.00, >10000 nM for CDK9, CDK7, CDK2, CDK4, CDK6 respectively. CDK9-IN-33 induces apoptosis. CDK9-IN-33 decreases the protein expression of RPB1 CTD Ser2, RPB1, MCL1. CDK9-IN-33 shows anti-tumor activity.