JNJ-26481585

Uses

JNJ-26481585 is an HDAC1, HDAC2, HDAC4, HDAC10, and HDAC11 inhibitor. Potent Histone deacetylase inhibitor.

Definition

ChEBI: N-hydroxy-2-[4-[[(1-methyl-3-indolyl)methylamino]methyl]-1-piperidinyl]-5-pyrimidinecarboxamide is a member of indoles.

Biological Activity

jnj-26481585 is a novel histone deacetylase (hdac) inhibitor that exerts a strong potency towards class i hdac (including hdac1, hdac2 and hdac3), with values of inhibition constant ic50 of 0.11, 0.33 and 4.8 nmol/l respectively, leading to strong anti-proliferative activities (ic50 ranging from 3.1 to 246 nmol/l) against a broad range of cancer cell lines including lung, breast, colon, prostate, brain and overian cancer cell lines. recent study results have shown that jnj-26481585 strongly induce the hdac1-suppressed p21waf1,cip1 promoter in vivo, histone h3 acetylation in tumor tissue and apoptosis in human colon cancer cell lines (both apc wild-type and mutant) in vitro.arts j, king p, mariën a, floren w, beliën a, janssen l, pilatte i, roux b, decrane l, gilissen r, hickson i, vreys v, cox e, bol k, talloen w, goris i, andries l, du jardin m, janicot m, page m, van emelen k, angibaud p. jnj-26481585, a novel "second-generation" oral histone deacetylase inhibitor, shows broad-spectrum preclinical antitumoral activity. clin cancer res. 2009;15(22):6841-6851

in vivo

target

HDAC1

IC 50

HDAC1: 0.11 nM (IC₅₀); HDAC2: 0.33 nM (IC₅₀); HDAC4: 0.64 nM (IC₅₀); HDAC10: 0.46 nM (IC₅₀); HDAC11: 0.37 nM (IC₅₀); HDAC3: 4.86 nM (IC₅₀); HDAC5: 3.69 nM (IC₅₀); HDAC8: 4.26 nM (IC₅₀); HDAC9: 32.1 nM (IC₅₀); HDAC6: 76.8 nM (IC₅₀); HDAC7: 119 nM (IC₅₀)