Identification | Back Directory | [Name]
FHD-286 | [CAS]
2671128-05-3 | [Synonyms]
FHD-286 1H-Pyrrole-3-carboxamide, N-[(1S)-2-[[4-[6-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-2-pyridinyl]-2-thiazolyl]amino]-1-(methoxymethyl)-2-oxoethyl]-1-(methylsulfonyl)- | [Molecular Formula]
C24H30N6O6S2 | [MOL File]
2671128-05-3.mol | [Molecular Weight]
562.66 |
Chemical Properties | Back Directory | [density ]
1.46±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 250 mg/mL (444.32 mM; Need ultrasonic) | [form ]
Solid | [pka]
7.18±0.50(Predicted) | [color ]
Off-white to light yellow | [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 |
Hazard Information | Back Directory | [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]
FHD-286 (1.5 mg/kg; oral administration; for 10 days) increases in IFNγ and Th1-type chemokine CXCL10 levels[2]. Animal Model: | B16F10 tumor-bearing mice[2] | Dosage: | 1.5 mg/kg | Administration: | Oral administration; for 10 days | Result: | Increased in IFNγ and Th1-type chemokine CXCL10 levels. |
| [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. |
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