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JNJ-7706621

Cat No.
CEI-0898
Description
JNJ-7706621 is pan-CDK inhibitor with the highest potency on CDK1/2 with IC50 of 9 nM/4 nM and showing >6-fold selectivity for CDK1/2 than CDK3/4/6. It also potently inhibits Aurora A/B and has no activity on Plk1 and Wee1.
CAS No.
443797-96-4
Molecular Weight
394.36
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
CDK1/Cyclin B, CDK2/Cyclin A, CDK2/Cyclin E, Aurora-A, Aurora-B
IC50
9 nM; 4 nM; 3 nM; 11 nM; 15 nM
Molecular Formula
C15H12F2N6O3S
Solubility
DMSO 79 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
JNJ-7706621 also shows some inhibition to VEGF-R2, FGF-R2, and GSK3β, with IC50 of 154-254 nM. JNJ-7706621 shows inhibitory effect on a panel of human cancer cell types, including HeLa, HCT-116, SK-OV-3, PC3, DU145, A375, MDA-MB-231, MES-SA, and MES-SA/Dx5, with IC50 of 112-514 nM, independent of p53, retinoblastoma, or P-glycoprotein status. JNJ-7706621 is several-fold less potent at inhibiting growth of normal cell types, including MRC-5, HASMC, HUVEC, and HMVEC, with IC50 of 3.67-5.42 μM. In HeLa or U937 cells, JNJ-7706621 (0.5-3 μM) delays exit from G1, arrests cells in G2-M, induces endoreduplication, activates apoptosis, and reduces colony formation. In a HeLa cell line, incremental treatment with increasing concentrations of JNJ-7706621 leads to a 16-fold resistance, which may be mediated by ABCG2.
In vivo
In mouse xenograft model of A375 melanoma human tumor, JNJ-7706621 (100 or 125 mg/kg) causes tumor regression.
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