BAY-1238097

InvivoChem Cat #:V4200CAS #:1564268-08-1Purity >=98%

Description: BAY-1238097 (the S-isomer of BAY-1238097) is a novel, potent and selective inhibitor of BET (bromodomain and extra-terminal) binding to histones and targeting the NFKB/TLR/JAK/STAT signalling pathways, MYC and E2F1-regulated genes, cell cycle regulation and chromatin structure. It has strong anti-proliferative activity in different AML (acute myeloid leukemia) and MM (multiple myeloma) models through down-regulation of c-Myc levels and its downstream transcriptome (IC50 < 100 nM in a TR-FRET assay). In vitro, BAY 1238097 showed strong inhibitory activity (IC50 < 100 nM) in a TR-FRET assay using BET BRD4 bromodomain 1 and an acetylated peptide derived from histone H4. In the NanoBRET assay, the interaction between BRD4, BRD3 or BRD2 and H4 was inhibited with IC50 values of 63 nM, 609 nM and 2430 nM, showing selectivity of the compound for BRD4. A strong reduction of c-Myc transcript and protein levels was observed in treated MOLM-13 (AML) and MOLP-8 (MM) cell lines. ChIP experiments performed in these models additionally revealed that BAY 1238097 prevented binding of BRD4 to c-Myc regulatory regions. In vivo, BAY 1238097 showed strong efficacy in the AML models THP-1, MOLM-13 and KG-1, with T/C between 13 and 20%. Overall, the compound was well tolerated at MTD, with body weight losses of 5-9% at nadir. BAY 1238097 was also active in MM models. Efficacy was observed against a human IGH-cyclin D1 translocated MOLP-8 model with a T/C of 3%, whereas the standard-of-care agents bortezomib and lenalidomide were inactive or poorly active. In this model, BAY 1238097 was well tolerated at 10 mg/kg applied over 14 days, with no body weight loss measured. BAY 1238097 was also active against the FGFR/MMSET translocated model NCIH929, with 19% T/C versus 49% T/C for the standard-of-care lenalidomide. The compound was well tolerated applied at 12 mg/kg for 9 days (maximum body weight loss 6%).

Description:

References: Cancer Research, 75(15 Suppl), 884.; Br J Haematol. 2017 Sep; 178(6):936-948.

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Related CAS#:1564269-85-7 (R-isomer)

-20C for 3 years in powder form

Synonym: S-isomer of BAY-1238097; BAY1238097; BAY-1238097; BAY 1238097; BAY 12-38097; BAY 123; BAY-123; BAY12-38097; BAY-12-38097
IUPAC/Chemical Name: (S)-7, 8-dimethoxy-N, 4-dimethyl-1-(4-(4-methylpiperazin-1-yl)phenyl)-4, 5-dihydro-3H-benzo[d][1, 2]diazepine-3-carboxamide
InChi Key: CJIPEACKIJJYED-KRWDZBQOSA-N
InChi Code: InChI=1S/C25H33N5O3/c1-17-14-19-15-22(32-4)23(33-5)16-21(19)24(27-30(17)25(31)26-2)18-6-8-20(9-7-18)29-12-10-28(3)11-13-29/h6-9, 15-17H, 10-14H2, 1-5H3, (H, 26, 31)/t17-/m0/s1
SMILES Code: O=C(N1N=C(C2=CC=C(N3CCN(C)CC3)C=C2)C4=CC(OC)=C(OC)C=C4C[CH]1C)NC