BAY 1238097

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

BAY 1238097 是一种新型 BET 溴结构域抑制剂，IC50 为 50 nM。

BAY 1238097 is a novel BET bromodomain inhibitor with IC50 of 50 nM, inhibits the interaction between BRD4, BRD3 or BRD2 and H4 with IC50 values of 63 nM, 609 nM and 2430 nM in the NanoBRET assay; shows selectivity of the compound for BRD4; strongly reduces c-Myc transcript and protein levels in MOLM-13 (AML) and MOLP-8 (MM) cell lines; exhibits strong efficacy in the AML models THP-1, MOLM-13 and KG-1.

BAY 1238097 shows 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 (IC50=63 nM), BRD3 or BRD2 (IC50=609 nM) and H4 (IC50=2430 nM) is inhibited. BAY 1238097 has in vitro anti-tumour activity in lymphoma models. BAY 1238097 affects the gene expression of GCB DLBCL cells. At the gene level, BTK, CCDC86, CCND2, CD19, CD27, FAIM, FCMR (FAIM3), IL7R, IRAK1, MAPK13, MYB, MYC, PDE4B, TNFRSF13B, TNFRSF17 are among the top downregulated genes. Beside histone-coding genes, the upregulated genes include CCL5, CDKN2C, CD69, JUN, and MKNK2.

BAY 1238097 shows strong efficacy in the AML and MM models. BAY 1238097 has in vivo anti-tumour activity in lymphoma models. BAY 1238097 is well tolerated at 10-15 mg/kg applied daily over 9-14 days in different disease models, with no obvious toxicity. Animal Model:Severe combined immunodeficiency (SCID) female mice (9-12 weeks old) inoculated subcutaneously into the right flank with 5×106 SU-DHL-8 cells/mouse suspended in 0.1 mL of matrigel or with O Dosage:15 mg/kg (maximal tolerated dose).Administration:Orally daily for 12 days (on day 21 post-tumour inoculation).Result:Showed strong efficacy in the AML models THP-1, MOLM-13 and KG-1, with T/C between 13 and 20%. Also active in MM models in a human IGH-cyclin D1 translocated MOLP-8 model with a T/C of 3%.

BAY1238097

Chromatin/Epigenetic

Bromodomain

Bromodomain

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1564268-08-1

451.571

C25H33N5O3

>98% (HPLC)

DMSO : 150 mg/mL 332.18 mM

O=C(N1N=C(C2=CC=C(N3CCN(C)CC3)C=C2)C4=CC(OC)=C(OC)C=C4C[C@@H]1C)NC

(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

(-20℃)

With Ice Pack

≥ 2 years