CDK2 Inhibitor

CDK12-IN-2 is a potent, selective and nanomolar CDK12 inhibitor (IC₅₀=52 nM) with good physicochemical properties. CDK12-IN-2 is also a strong CDK13 inhibitor due to CDK13 is the closest homologue of CDK12. CDK12-IN-2 shows excellent kinase selectivity for CDK12 over CDK2, 9, 8, and 7. CDK12-IN-2 inhibits the phosphorylation of Ser2 in the C-terminal domain of RNA polymerase II. CDK12-IN-2 can be used an excellent chemical probe for functional studies of CDK12.

FN-1501 is a potent inhibitor of FLT3 and CDK, with IC₅₀s of 2.47, 0.85, 1.96, and 0.28 nM for CDK2/cyclin A, CDK4/cyclin D1, CDK6/cyclin D1 and FLT3, respectively. FN-1501 has anticancer activity.

Lerociclib dihydrochloride (G1T38 dihydrochloride) is a potent and selective inhibitor of CDK4/CDK6, with IC₅₀s of 1 nM and 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.

BS-181 hydrochloride is a highly selective CDK7 inhibitor with IC₅₀ of 21 nM, and > 40-fold selective for CDK7 than CDK1, 2, 4, 5, 6, or 9.

GW8510 is a potent cyclin-dependent kinase-2 (CDK2) inhibitor. GW8510 is also a ribonucleotide reductase M2 (RRM2) inhibitor. GW8510 exhibits neuroprotective and anticancer activities.

MC180295 ((rel)-MC180295) is a potent and selective CDK9-Cyclin T1 inhibitor, with an IC₅₀ of 5 nM, at least 22-fold more selective for CDK9 over other CDKs. MC180295 also inhibits GSK-3α and GSK-3β. MC180295 ((rel)-MC180295) has potent anti-tumor effect.

Lerociclib (G1T38) is a potent and selective inhibitor of CDK4/6, with IC₅₀s of 1 nM, 2 nM for CDK4/CyclinD1 and CDK6/CyclinD3, respectively.

CDK5-IN-3 (compound 11) is a potent CDK5 inhibitor, with IC₅₀s of 0.6 nM and 18 nM for CDK5/p25 and CDK2/CycA, respectively. CDK5-IN-3 can be used for the research of autosomal dominant polycystic kidney disease (ADPKD).

K00546 is a potent CDK1 and CDK2 inhibitor with IC₅₀s of 0.6 nM and 0.5 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. K00546 is also a potent CDC2-like kinase 1 (CLK1) and CLK3 inhibitor with IC₅₀s of 8.9 nM and 29.2 nM, respectively.

Tudociclib is a CDK2 inhibitor with an IC₅₀ value ≤20 nM. Tudociclib modulates CDK2 activity to influence cell cycle regulation. Tudociclib can be used for the research of cancer.

PKCζ-IN-1 is a PKCζ-selective inhibitor with an IC₅₀ of 5.18 nM against human PKCζ. PKCζ-IN-1 also inhibits CDK2 with an IC₅₀ of 1.04 μM. PKCζ-IN-1 is applicable to research related to immune and inflammatory diseases.

YK-2168 is a potent and selective CDK9 inhibitor with an IC50 of 5.9 nM. YK-2168 inhibits phosphorylation of the CDK9 substrate pS2-RNA Pol II C-terminal domain. YK-2168 induces apoptosis in tumor cells, suppresses expression of CDK9-regulated genes including MYC and Mcl1, and inhibits tumor growth in CDX mice models. YK-2168 can be used for the research of cancer, such as leukemia.

Ipivivint (Compound 38) is an orally active and potent CDC-like kinase (CLK) inhibitor with EC₅₀ of 1 nM and 7 nM for CLK2 (human) and CLK3 (human), respectively. Ipivivint also inhibits the Wnt pathway (EC50=13 nM) and tyrosine phosphorylation-regulated kinase 1A (human) (EC₅₀=5 nM).

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

YKL-5-124 TFA 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 TFA is >100-fold greater selective for CDK7 than CDK9 and CDK2, and inactive against CDK12 and CDK13. YKL-5-124 TFA induces a strong cell-cycle arrest, inhibits E2F-driven gene expression, and exhibits little effect on RNA polymerase II phosphorylation status.

TMX-3013 is a CDK inhibitor capable of inhibiting the activity of CDK1, CDK2, CDK4, CDK5, and CDK6, with IC₅₀ values of 0.9 nM, <0.5 nM, 24.5 nM, 0.5 nM, and 15.6 nM, respectively. TMX-3013 can be used as a target protein ligand, conjugated with the PROTAC linker and the CRBN ligand Thalidomide (HY-14658) for the synthesis of PROTAC TMX-2138 (HY-164906). TMX-3013 can also act as an effector ligand, binding to target proteins HaloTag or FKBP, and can be used in the synthesis of regulated induced proximity targeting chimeras (RIPTACs).

AZD5597 is an inhibitor of CDK with IC₅₀ values of both 2 nM for CDK1 and CDK2. AZD5597 can inhibit the proliferation of tumor cells and has anti-tumor activity.

Desmethylglycitein (4',6,7-Trihydroxyisoflavone), a metabolite of daidzein, sourced from Glycine max with antioxidant, and anti-cancer activities. Desmethylglycitein binds directly to CDK1 and CDK2 in vivo, resulting in the suppresses CDK1 and CDK2 activity. Desmethylglycitein is a direct inhibitor of protein kinase C (PKC)α, against solar UV (sUV)-induced matrix matrix metalloproteinase 1 (MMP1). Desmethylglycitein binds to PI3K in an ATP competitive manner in the cytosol, where it inhibits the activity of PI3K and downstream signaling cascades, leading to the suppression of adipogenesis in 3T3-L1 preadipocytes.

ECI830 (CDK2-IN-37) is an orally active, ATP-competitive and highly selective CDK2 inhibitor. ECI830 shows high selectivity over other CDK family members. ECI830 can be used for the study of HR+/HER2- breast cancer and CCNE1-amplified tumors (such as ovarian cancer and lung cancer).

AMG 925 is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC₅₀s of 2±1 nM and 3±1 nM, respectively.