JNJ-7706621

Description

JNJ-7706621 is a dual inhibitor of cyclin-dependent kinases (CDKs) and Aurora kinases. It potently inhibits Cdk1/cyclin B, Cdk2/cyclin A, Cdk2/cyclin E, Cdk3/cyclin E, Cdk4/cyclin D1, Cdk6/cyclin D1, Aurora A, and Aurora B in vitro (IC₅₀s = 9, 4, 3, 58, 253, 175, 11, and 15 nM, respectively). It shows selectivity for these enzymes over a panel of other receptors and kinases, although it exhibits submicromolar inhibition of VEGF and FGF receptors, as well as GSK3β. JNJ-7706621 blocks the growth of a large variety of cancer cell lines (IC₅₀ values range from 112 to 514 nM), with lower potency against normal cells (IC₅₀ values between 3.67 and 5.42 μM). It induces the regression of A375 melanoma human tumor xenografts in mice. JNJ-7706621 is a substrate for the ATP-binding cassette transporter G2, also known as breast cancer resistance protein.

Uses

JNJ-770662 is a broad spectrum inhibitor of cyclin-dependent kinases and aurora kinases including CDK1/Cyclin B, CDK2/Cyclin A, CDK2/Cyclin E, Aurora-A and Aurora-B. JNJ-770662 has been shown to induce growth suppression and mitotic defects, these results suggest that JNJ-7706621 could be useful for cell cycle analysis and therapy of various cancers, including Ewing''s sarcoma.

Definition

ChEBI: 4-[[5-amino-1-[(2,6-difluorophenyl)-oxomethyl]-1,2,4-triazol-3-yl]amino]benzenesulfonamide is a sulfonamide.

in vivo

target

CDK1

IC 50

CDK6/cyclinD1: 175 nM (IC₅₀); CDK2/cyclinE: 3 nM (IC₅₀); Cdk4/cyclin D1: 253 nM (IC₅₀); Cdk1/cyclin B: 9 nM (IC₅₀); cdk2/cyclin A: 4 nM (IC₅₀); CDK3/Cyclin E: 58 nM (IC₅₀); Aurora A: 11 nM (IC₅₀); Aurora B: 15 nM (IC₅₀); VEGF-R2: 154 nM (IC₅₀); VEGF-R1: 6400 nM (IC₅₀); VEGF-R3: 735 nM (IC₅₀); FGF-R1: 575 nM (IC₅₀); FGF-R2: 226 nM (IC₅₀); GSK3β: 254 nM (IC₅₀)