FHD-286 Chemical Properties

Density 

1.46±0.1 g/cm3(Predicted)

storage temp. 

Store at -20°C

solubility 

DMSO : 250 mg/mL (444.32 mM; Need ultrasonic)

pka

7.18±0.50(Predicted)

form 

Solid

color 

Off-white to light yellow

InChI

InChI=1S/C24H30N6O6S2/c1-15-10-29(11-16(2)36-15)21-7-5-6-18(25-21)20-14-37-24(27-20)28-23(32)19(13-35-3)26-22(31)17-8-9-30(12-17)38(4,33)34/h5-9,12,14-16,19H,10-11,13H2,1-4H3,(H,26,31)(H,27,28,32)/t15-,16+,19-/m0/s1

InChIKey

JBLQNFBXKOAIHG-FCEWJHQRSA-N

SMILES

N1(S(C)(=O)=O)C=CC(C(N[C@@H](COC)C(NC2=NC(C3=NC(N4C[C@H](C)O[C@H](C)C4)=CC=C3)=CS2)=O)=O)=C1

FHD-286 Usage And Synthesis

Description

FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2), two highly similar proteins that are the ATPases, or the catalytic engines of the BAF complex, one of the critical regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumour activity across a broad range of malignancies, including hematologic and solid tumours. FHD-286 is being developed for relapsed and/or refractory AML.

Uses

FHD-286 is a selective, oral inhibitor of SMARCA4/SMARCA2 ATPase (BRG1 and BRM) inhibitor. FHD-286 has the potential for the research of BAF (BRG1/BRM-associated factor)-related disorders such as acute myeloid leukemia[1].

in vivo

References

[1] Warren C. Fiskus, et al. Abstract 1140: Pre-clinical efficacy of targeting BAF complexes through inhibition of the dual ATPases BRG1 and BRM by FHD-286 in cellular models of AML. Cancer Res (2023) 83 (7_Supplement): 1140.
[2] Kana Ichikawa, et al. Synergistic efficacy of the BRM/BRG1 ATPase inhibitor, FHD-286, and anti-PD-1 antibody in mouse syngeneic tumor models.