CDK5 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.

Dinaciclib (SCH 727965) is a potent inhibitor of CDK, with IC₅₀s of 1 nM, 1 nM, 3 nM, and 4 nM for CDK2, CDK5, CDK1, and CDK9, respectively.

(R)-Roscovitine (Seliciclib) is an orally bioavailable, selective and BBB-permeable CDKs inhibitor with IC₅₀s of 0.2 μM, 0.65 μM, and 0.7 μM for CDK5, Cdc2, and CDK2, respectively.

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.

Kenpaullone is a potent inhibitor of CDK1/cyclin B and GSK-3β, with IC₅₀s of 0.4 μM and 23 nM, and also inhibits CDK2/cyclin A, CDK2/cyclin E, and CDK5/p25 with IC₅₀s of 0.68 μM, 7.5 μM, 0.85 μM, respectively. Kenpaullone, a small molecule inhibitor of KLF4, reduces self-renewal of breast cancer stem cells and cell motility in vitro.

17β-HSD10/CDK5-IN-1 is a poent dual 17β-HSD10 and CDK5 inhibitor with IC₅₀s of 2.44 and 0.26 μM for 17β-HSD10 and CDK5, respectively. 17β-HSD10/CDK5-IN-1 reduces ROS accumulation, attenuates pathological Tau phosphorylation, reduces Aβ plaque deposition, and ameliorates cognitive deficits in Alzheimer's mice. 17β-HSD10/CDK5-IN-1 can be used for the research of Alzheimer's disease.

GSK 3 Inhibitor IX (6-Bromoindirubin-3'-oxime; BIO) is a potent, selective, reversible and ATP-competitive inhibitor of GSK-3α/β and CDK1-cyclinB complex with IC₅₀s of 5 nM/320 nM/80 nM for (GSK-3α/β)/CDK1/CDK5, respectively.

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.

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 .

NG 52 is a potent, cell-permeable, selective, ATP-compatible and orally active Cdc28p and Pho85p kinase inhibitor with IC₅₀s of 7 μM and 2 μM, respectively. NG 52 also inhibits the activity of phosphoglycerate kinase 1 (PGK1) with an IC₅₀ of 2.5 μM. NG 52 is inactive against yeast kinases Kin28p, Srb10, and Cak1p.

(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.

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.

Purvalanol A is a potent CDK inhibitor, which inhibits cdc2-cyclin B, cdk2-cyclin A, cdk2-cyclin E, cdk4-cyclin D1, and cdk5-p35 with IC₅₀s of 4, 70, 35, 850, 75 nM, resepctively.

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.

R547 is a potent, selective and orally active ATP-competitive CDK inhibitor, with K_is of 2 nM, 3 nM and 1 nM for CDK1/cyclin B, CDK2/cyclin E and CDK4/cyclin D1, respectively.

Alsterpaullone (9-Nitropaullone) is a potent CDK inhibitor, with IC₅₀s of 35 nM, 15 nM, 200 nM and 40 nM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E and CDK5/p35, respectively. Alsterpaullone also competes with ATP for binding to GSK-3alpha/GSK-3beta with IC₅₀s of both 4 nM. Alsterpaullone has antitumor activity, and possesses potential for the study in neurodegenerative and proliferative disorders. Alsterpaullone induces apoptosis in leukemia cell line.

PHA-793887 is a potent, ATP-competitive CDK inhibitor, can inhibit Cdk2, Cdk1, Cdk4, and Cdk9 with IC₅₀s of 8 nM, 60 nM, 62 nM and 138 nM, respectively, and also inhibits glycogen synthase kinase 3β with an IC₅₀ of 79 nM.

Atuveciclib (BAY-1143572) is a potent and highly selective, oral PTEFb/CDK9 inhibitor. Atuveciclib (BAY-1143572) inhibits CDK9/CycT1 with an IC₅₀ of 13 nM.