GNE-781 Inhibitor

Solid. Powder

98.00%

Store at -20 degree C for 3 years powder
-80 degree C for 2 years in solvent

525.59

DMSO: 100mg/mL (190.26mM) Need ultrasonic
(<1mg/ml refers to the product slightly soluble or insoluble)

C27H33F2N7O2

O=C(N1CCC(N(C2CCOCC2)N=C3N4CCCC5=C4C=C(C(F)F)C(C6=CN(C)N=C6)=C5)=C3C1)NC

1936422-33-1

CBP: ic50 0.94nM
BRET: ic50 6.2nM
BRD41: ic50 5100nM

GNE-781 is a highly potent and selective inhibitor of CBP that is efficacious in a MOLM-16 AML xenograft model. GNE-781 shows antitumor activity in an AML tumor model and is also shown to reduce Foxp3 transcript levels in a dose-dependent manner and it also shows moderate to low clearance in vivo in all species evaluated, with acceptable oral bioavailability. The effect of GNE-781 is determined in an in vivo PK/PD experiment using a MOLM-16 (adult AML cell line) xenograft mouse model. GNE-781(3 and 30mg/kg; Single doses) are given in MOLM-16 tumor-bearing animals, and samples are collected at time points covering 2-24 hours. Upon tumor establishment, Administration with GNE-781(3-30mg/kg; twice daily). Single-agent efficacy is observed at all doses, as evidenced by inhibition of MOLM-16 tumor growthours. Tumor growth inhibition (%TGI) is 73%, 71%, and 89% at 3, 10, and 30mg/kg, respectively. All doses of GNE-781 are well tolerated over the 21-day dosing window, with a maximal body weight loss of 3.7%. Tumor RNA is generated and used to assess MYC transcript by quantitative RT-PCR relative to vehicle-treated animals. At doses as low as 3mg/kg at 2 and 8 hours, suppression of MYC is observed, with maximal suppression observed at 10 and 30mg/kg at 2 hours (87% and 88% inhibition, respectively).

Chromatin/Epigenetic; Epigenetic Reader Domain; Epigenetics