3008577-34-9
Chemical Structure
FHD-909
Synonym(s): LY4050784
- CAS No.: 3008577-34-9
- Formula:C29H25F2N5O5S
- Molecular Weight:593.60
InChIKey: FTVMRDJXYKJEPP-RUZDIDTESA-N
SMILES: O=C(C1=CC(F)=C(OCC[C@@H](S2(=O)=O)F)C2=C1)NCC3=CC4=C(C=N3)C=CC(N5C6=NC(C7CC7)=CC=C6OCC5)=N4
Biological Activity: FHD-909 (LY4050784) is an orally active and selective SMARCA2 (BRM) ATPase inhibitor. FHD-909 potently inhibits purified BRM ATPase with an IC50 of 0.0025 μM and exhibits 35.69-fold selectivity for BRM over purified SMARCA4 (BRG1) ATPase. FHD-909 induces synthetic lethality, suppresses cell proliferation, modulates target gene expression, and achieves remarkable tumor growth inhibition and regression in SMARCA4-mutant cancer cells and xenograft models. FHD-909 can be used for the research of SMARCA4/BRG1-mutant cancers, advanced solid tumors, and BAF complex-related disorders[1][2][3][4].
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FHD-909 | FHD-909 (LY4050784) is an orally active and selective SMARCA2 (BRM) ATPase inhibitor. FHD-909 potently inhibits purified BRM ATPase with an IC50 of 0.0025 μM and exhibits 35.69-fold selectivity for BRM over purified SMARCA4 (BRG1) ATPase. FHD-909 induces synthetic lethality, suppresses cell proliferation, modulates target gene expression, and achieves remarkable tumor growth inhibition and regression in SMARCA4-mutant cancer cells and xenograft models. FHD-909 can be used for the research of SMARCA4/BRG1-mutant cancers, advanced solid tumors, and BAF complex-related disorders. | |||||||||||||||||||||
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- [1]. Brooks NA. LY4050784, a selective inhibitor of SMARCA2, demonstrates synergistic activity in combinations with pembrolizumab or KRAS inhibitors. Proceedings of the American Association for Cancer Research Annual Meeting 2025; 2025 Apr 25-30; Chicago, IL. Proc Am Assoc Cancer Res. 2025;66.
- [2]. Yap T. Abstract CT109: A first-in-human phase 1 study of LY4050784, an oral, potent, and selective SMARCA2 inhibitor, in patients with advanced solid tumors with SMARCA4 alterations (Trial in Progress). Cancer Res. 2025;85(8_Supplement_2):CT109.
- [3]. Lee JY, et al. Discovery of LY4050784 (FHD-909), a selective BRM (SMARCA2) ATPase inhibitor for the treatment of BRG1(SMARCA4) mutant cancers. Mol Cancer Ther. 2024;23(6_Suppl):PR015.
- [4]. Schiller SE. Compounds and uses thereof, WO, WO2023220219A1, 2023-11-16.
Keywords
