CDK5 Inhibitor

NSC693868 is a selective inhibitor of CDK1 and CDK5 with IC₅₀s of 600 nM and 400 nM, respectively. NSC693868 less potently inhibits GSK3β with an IC₅₀ of 1 µM) and does not block CDC25 activity. NSC693868 is used to help define the roles of CDK1 and CDK5 in various signaling pathways.

GSK-3 inhibitor 4 is an orally active and brain-penetrant inhibitor of GSK-3, CDK2, and CDK5, with IC₅₀ values of 0.56 nM (GSK-3β), 0.45 nM (GSK-3α), 0.47 μM, and 0.68 μM, respectively. GSK-3 inhibitor 4 effectively reduces the phosphorylation level of Tau protein. GSK-3 inhibitor 4 can be used in Alzheimer's disease (AD) studies.

(R)-DRF053 dihydrochloride is a potent casein kinases 1 (CK1), CDK1/cyclin B and CDK5/p25 inhibitor with IC₅₀s of 14 nM, 220 nM and 80 nM, respectively. (R)-DRF053 dihydrochloride prevents the CK1-dependent production of amyloid-beta in a cell model.

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.

PNU112455A hydrochloride is an ATP-competitive CDK2 and CDK5 inhibitor. PNU112455A hydrochloride binds to the ATP site of CDK2 and CDK5 with K_ms of 3.6 and 3.2 μM, respectively.

Manzamine A, an orally active beta-carboline alkaloid, inhibits specifically GSK-3β and CDK-5 with IC₅₀s of 10.2 μM and 1.5 μM, respectively. Manzamine A targets vacuolar ATPases and inhibits autophagy in pancreatic cancer cells. Manzamine A has antimalarial and anticancer activities. Manzamine A also shows potent activity against HSV-1.

(R)-(+)-O-Demethylbuchenavianine is an inhibitor for Cyclin-dependent kinases (CDK). (R)-(+)-O-Demethylbuchenavianine inhibits CDK1, CDK5, glycogen synthase kinase-3 (GSK3), cdc2-like kinase (CLK1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), with IC₅₀s of 1.1, 0.95, >10, >10 and >10 μM, respectively.

CDK1-IN-5 (10h) is a selective CDK1 inhibitor with IC₅₀s of 42.19, 188.71 and 354.15 nM for CDK1, CDK2 and CDK5, respectively. CDK1-IN-5 inhibits growth of cancer cells by affecting cell cycle. CDK1-IN-5 can be used for the research of cancer.

CDK1-IN-3 (8g) is a selective CDK1 inhibitor with IC₅₀s of 36.8, 305.17 and 369.37 nM for CDK1, CDK2 and CDK5, respectively. CDK1-IN-3 inhibits the growth of cancer cells by affecting cell cycle. CDK1-IN-3 can be used for the research of cancer.

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-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.

Aloisine A (RP107) is a a potent cyclin-dependent kinase (CDK) inhibitor with IC₅₀s of 0.15 μM, 0.12 μM, 0.4 μM, 0.16 μM for CDK1/cyclin B, CDK2/cyclin A, CDK2/cyclin E, CDK5/p35, respectively. Aloisine A ininhibits GSK-3α (IC₅₀=0.5 μM) and GSK-3β (IC₅₀=1.5 μM). Aloisine A stimulates wild-type CFTR and mutated CFTR, with submicromolar affinity by a cAMP-independent mechanism. Aloisine A has the potential for CFTR-related diseases, including cystic fibrosis research.

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.

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.

GSK3β/CDK5/CK1 IN-1 is a kinase inhibitor targeting GSK-3, CDK5, and CK1. GSK3β/CDK5/CK1 IN-1 is used in the research of cognitive, neurodegenerative, or neurological diseases or disorders.

CDK5-IN-2 (compound 15) is a highly selective CDK5 inhibitor with IC₅₀s of 0.2 and 23 for CDK5/p25 and CDK2/CycA, respectively.

BLINK11 is a BBB-penetrant CDK5 inhibitor. BLINK11 lowers CDK5 activity for both complexes CDK5/p35 (IC₅₀ = 17.09 nM) and CDK5/p25 (IC₅₀ = 14.69 nM). BLINK11 offers anti-diabetic and neuroprotective benefits. BLINK11 lowers blood glucose, enhances cognition, and reduces neurodegeneration in T2D mice.

CDK7-IN-20 is a potent, selective and irreversible CDK7 (CDK) inhibitor with an IC₅₀ value of 4 nM. CDK7-IN-20 displays >206-fold selectivity for CDK7 over CDK1, CDK2, CDK3, CDK5, CDK6, CDK9 and CDK12 . CDK7-IN-20 has the potential for autosomal dominant polycystic kidney disease (ADPKD) research.

KB-0742 hydrochloride is a potent, selective and orally active CDK9 inhibitor with an IC₅₀ of 6 nM for CDK9/cyclin T1. KB-0742 hydrochloride is selective for CDK9/cyclin T1 with >50-fold selectivity over other CDK kinases. KB-0742 hydrochloride has potent anti-tumor activity.

Multi-kinase-IN-7 is a multikinase inhibitor with IC₅₀s of 2.19, 2.95, 3.59 and 9.31 μM against EGFR, VEGFR2, TrKA and CDK2, respectively. Multi-kinase-IN-7 shows moderate and weaker activity against FAK, AKT1, GSK3β and CDK5 with IC₅₀ values of 6.3, 9.2, 11.7 and 23.4 μM, respectively. Multi-kinase-IN-7 displays broad spectrum anti­proliferative potential against NCI cancer cell lines. Multi-kinase-IN-7 induces cell cycle arrest, apoptosis and necrosis. Multi-kinase-IN-7 Inhibitor can be used for the study of breast cancer.