CDK1 Inhibitor

TrkA Inhibitor (Compound 18) is a CDK2 inhibitor with an IC₅₀ of 0.69  μM over CDK1. TrkA Inhibitor can be used for chemotherapy-induced alopecia research.

CDK4/6-IN-14 is a potent and highly selective CDK4 and CDK6 (CDK) inhibitor with IC₅₀s of 10 nM and 16 nM, respectively. CDK4/6-IN-14 exhibits more than 60-fold selectivity over CDKs 1, 2, 7, and 9, and shows high selectivity among other 205 kinases.

CDC20/HSP90-IN-1 (Compound 2b) is a Cdc20/Hsp90 inhibitor with a K_d of 16.2 μM for Cdc20 and a K_d of 0.241 μM for Hsp90α. CDC20/HSP90-IN-1 exerts potent antitumor activity through reducing p53-mediated Cdc20, upregulating Bim, downregulating Cyclin B1 expression, and disturbing B-Raf and AKT pathways via destroying Hsp90 chaperone function. CDC20/HSP90-IN-1 overcomes Vemurafenib (HY-12057)-induced resistant melanoma.

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.

CDK4/6/HDAC-IN-1 (Compound N14) is a dual-targeting inhibitor of CDK4/6 and HDAC (IC₅₀: CDK4 = 7.23 nM, CDK6 = 13.20 nM, HDAC1 = 55.66 nM, HDAC6 = 48.38 nM). CDK4/6/HDAC-IN-1 induces cell Apoptosis and G0/G1 phase arrest through HDAC-p21-CDK signaling pathway. CDK4/6/HDAC-IN-1 inhibits hepatocellular carcinoma.

CDK/HDAC-IN-2 is a potent HDAC/CDK dual inhibitor with IC₅₀ of 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM for HDAC1, HDAC2, HDAC3, HDAC6,8, CDK1, CDK2, CDK4,6,7, respectively. CDK/HDAC-IN-2 shows excellent antiproliferative activities. CDK/HDAC-IN-2 induces apoptosis and cell cycle arrest at G2/M phase. CDK/HDAC-IN-2 shows potent antitumor efficacy.

KDM1/CDK1-IN-1 (compound 4) is a potent KDM1 and CDK1 inhibitor, with IC₅₀ values of 0.096 and 0.078 μM, respectively.KDM1/CDK1-IN-1 induces cell cycle arrest at G2/M phase and apoptosis in HOP-92 cells. KDM1/CDK1-IN-1 exhibits potent cytotoxic activity against the CCRF-CEM, HOP-92 and Hep-G2 cells, with IC₅₀ values of 16.34, 3.45 and 7.79 μM, respectively.

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.

ZNL-02-096 is a selective Wee1 PROTAC degrader. ZNL-02-096 binds to CRBN and Wee1 to form a ternary complex, inducing CRBN- and proteasome-dependent ubiquitination and proteasomal degradation of Wee1. ZNL-02-096 inhibits recombinant PLK1 with an IC₅₀ of 102 nM, but does not induce its degradation in cells. ZNL-02-096 induces G₂/M phase arrest, Apoptosis, transient integrated stress response, upregulation of ATF4, and phosphorylation of GCN2. ZNL-02-096 reduces Tyr15 phosphorylation of CDK1. ZNL-02-096 can be used in research related to ovarian cancer, acute lymphoblastic leukemia, triple-negative breast cancer, multiple myeloma, and pancreatic ductal adenocarcinoma.

CDK2-IN-47 is a potent CDK2 inhibitor with an IC₅₀ of 0.21 μM. CDK2-IN-47 exhibits outstanding anticancer activity against MCF-7, HCT-116, and MGC-803 cell lines. CDK2-IN-47 effectively induces G1 cell cycle arrest, retinoblastoma protein (Rb) dephosphorylation, and significant apoptosis. CDK2-IN-47 can be used for the studies of breast cancer, colorectal cancer and gastric cancer.

CDK2-IN-55 (Compound 12c) is a CDK2 inhibitor with an IC₅₀ value of 4.7 nM. CDK2-IN-55 also has a strong inhibitory effect on CDK1 (IC₅₀ = 26.3 nM), moderate inhibitory effects on Aurora A (IC₅₀ = 92.0 nM) and CDK9 (IC₅₀ = 288 nM), and very weak inhibitory activities on CDK4, CDK6, DYRK1A, and GSK3β (IC₅₀ > 1000 nM). CDK2-IN-55 shows strong anti-proliferative activity against various cancer cell lines, inducing cell cycle arrest and apoptosis. CDK2-IN-55 can be used for research on colorectal cancer, lung cancer, and cervical cancer.

8‑Acetonyldihydronitidine is a naturally occurring benzophenanthridine alkaloid with antibacterial, antifungal, and anti-proliferative activities against colorectal cancer cells. 8‑Acetonyldihydronitidine inhibits Staphylococcus aureus and exerts a potent antifungal effect against Cladosporium cladosporioides. 8‑Acetonyldihydronitidine activates the p53 signaling pathway, upregulates the expression of target genes including p21, BAX, and FAS, downregulates cyclin A and cyclin B, and induces cell cycle arrest and apoptosis, thereby suppressing the proliferation of colorectal cancer cells. 8‑Acetonyldihydronitidine is used in research related to colorectal cancer, fungal infections, and bacterial infections.

BMI-1026 is a cyclin-dependent kinase 1 (Cdk1) inhibitor with IC₅₀ of 2.3 nM. BMI-1026 induces apoptosis by arresting the G2-M phase.

CDK1-IN-8 is a CDK1 inhibitor. CDK1-IN-8 inhibits cell migration, induces apoptosis, and arrests the cell cycle at the G2/M phase. CDK1-IN-8 leads to a significant downregulation of CDK1 protein levels in HepG2 cells. CDK1-IN-8 can be used for the study of hepatocellular carcinoma.

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.

CDK2-IN-48 (Compound 109) is a CDK2 inhibitor with IC₅₀ values for CDK2 and CDK1 of respectively < 0.05 and > 1 μM. CDK2-IN-48 can be used for the study of CDK2-dependent cancers.

BLINK15 is a BBB-penetrant CDK5 inhibitor. BLINK15 lowers CDK5 activity for both complexes CDK5/p35 (IC₅₀ = 29.34 nM) and CDK5/p25 (IC₅₀ = 12.08 nM). BLINK15 offers anti-diabetic and neuroprotective benefits. BLINK15 lowers blood glucose, enhances cognition, and reduces neurodegeneration in T2D mice.

PKMYT1-IN-12 (Compound 4) is a selective inhibitor of PKMYT1, with an IC₅₀ of 2.6 nM. PKMYT1-IN-12 can effectively inhibit the phosphorylation of CDK1, with an IC₅₀ of 44 nM. PKMYT1-IN-12 is a target protein ligand that can be used for the synthesis of PROTAC D16-M1P2 (HY-180485).

3-Methylthienyl-carbonyl-JNJ-7706621 is a potent and selective inhibitor of cyclin-dependent kinase (CDK), with IC₅₀s of 6.4 nM and 2 nM for CDK1/cyclin B and CDK2/cyclin A, respectively. 3-Methylthienyl-carbonyl-JNJ-7706621 also shows potent inhibition of GSK-3 (IC₅₀=0.041 μM) and modest potency against CDK4, VEGF-R2, and FGF-R2 (IC₅₀=0.11, 0.13, 0.22 μM, respectively). 3-Methylthienyl-carbonyl-JNJ-7706621 can be used for the research of cancer.

BMS-357075 is a pan-CDK inhibitor with CDK1 IC₅₀ 18 nM, CDK2 IC₅₀ 3 nM, CDK4 IC₅₀ 26 nM. BMS-357075 induces cytotoxicity in human ovarian cancer A2780 cells. BMS-357075 exhibits anticancer activity in mice against P388 murine leukemia. BMS-357075 can be used for the research of leukemia.