Uses
BRM/BRG1 ATP Inhibitor-1 (compound 14) is an orally active allosteric dual brahma homolog (BRM)/SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily A member 2 (SMARCA2) and brahma related gene 1 (BRG1)/SMARCA4 ATPase activity inhibitor, both IC50s are below 0.005 μM. BRM/BRG1 ATP Inhibitor-1 has anticancer activity[1].
Biological Activity
NVP-RXI570 is an orally active, potent, and selective allosteric dual inhibitor of BRM ((SMARCA2) and BRG1 (SMARCA4) th at th at downregulates BRM-dependent gene expression. NVP-RXI570 exhibits antiproliferative activity in a BRG1 mutant-lung-tumor xenograft model.
in vivo
BRM/BRG1 ATP Inhibitor-1 (compound 14) (oral administration, 7.5 or 20 mg/kg, everyday, 3 weeks) can inhibit tumor growth and inhibit KRT80 expression in a dose-dependent manner[1].
| Animal Model: | Female athymic nude mice with RERF-LC-AI tumor xenografts[1] |
| Dosage: | 7.5 mg/kg, 20 mg/kg |
| Administration: | Oral administration; everyday; 3 weeks |
| Result: | Inhibited tumor growth by 21% and 55% at doses of 7.5 mg/kg and 20 mg/kg, respectively.
Inhibited KRT80 expression by up to 90% at 20 mg/kg for 7 hours after administration.
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References
[1] Papillon JPN, et al. Discovery of Orally Active Inhibitors of Brahma Homolog (BRM)/SMARCA2 ATPase Activity for the Treatment of Brahma Related Gene 1 (BRG1)/SMARCA4-Mutant Cancers. J Med Chem. 2018 Nov 21;61(22):10155-10172 DOI:
10.1021/acs.jmedchem.8b01318
