BI-9564

• CAT Number: I002430
• CAS Number: 1883429-22-8
• Molecular Formula: C₂₀H₂₃N₃O₃
• Molecular Weight: 353.41
• Purity: ≥95%
• Synonyms: 4-(4-((dimethylamino)methyl)-2,5-dimethoxyphenyl)-2-methyl-2,7-naphthyridin-1(2H)-one
• Target: Bromodomain
• Solubility: DMSO: ≥ 7.2 mg/mL (Need warming)
• Storage: Store at -20°C
• IC50: Kd: 20 nM (BRD9)
• InChI: InChI=1S/C20H23N3O3/c1-22(2)11-13-8-19(26-5)15(9-18(13)25-4)17-12-23(3)20(24)16-10-21-7-6-14(16)17/h6-10,12H,11H2,1-5H3
• InChIKey: BJFSUDWKXGMUKA-UHFFFAOYSA-N
• SMILES: CN1C=C(C2=C(C1=O)C=NC=C2)C3=CC(=C(C=C3OC)CN(C)C)OC

BI-9564 is a selective, and cell-permeable BRD9 BD inhibitor, with Kd of 5.9 nM for BRD9, and IC50 of > 100 μM for BET family.IC50 value: Kd: 20 nM (BRD9)Target:In vitro: BI-9564 ( <5 μM) show no activity against 324 kinases, and at 10 μM, an inhibition >40% was observed for only 2 out of 55 GPCRs. BI-9564 has antiproliferative effect on human acute myeloid eosinophilic leukemia cell line EOL-1, with EC50 of 800 nM[1]. BI-9564 shows KD of 73 nM for BRD7, and is >10-fold more selective for BRD9 over the highly homologues bromodomain BRD7, which has been implied as a tumor suppressor and is down-regulated in cancer cells[2].In vivo: BI-9564 (180 mg/kg, p.o.) shows attractive ADME/PK profiles for in vivo proof-of-concept studies. BI-9564 results in a modest but significant additional survival benefit of 2 days compared to survival of the control group in a xenograft model of human AML[1].

Reference

[1]. Martin LJ, et al. Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75.

[2]. Rezaul M. Karim, et al. An Advanced Tool To Interrogate BRD9. J. Med. Chem., 2016, 59 (10), pp 4459-4461