(brm)/smarca2

BRM BRG1 ATP Inhibitor-1 is an allosteric dual Brahma homolog (BRM) SWI SNF related matrix-associated actin-dependent regulator of chromatin subfamily A member 2 (SMARCA2) and BRG1 SMARCA4 ATPase activity inhibitor (IC50s<0.005 μM).

SMARCA2-IN-6 is a potent inhibitor of SMARCA2 (also known as BRM), exhibiting an IC50 of less than 5 nM against both SMARCA2 and SMARCA4. Additionally, this compound suppresses the expression of the KRT80 gene in H1299 cells with an IC50 of 26 nM and inhibits the proliferation of SKMEL5 cells carrying a BRG1 mutation with an IC50 value of 13 nM.

PROTAC SMARCA2 degrader-29 (Example 87) is a potent PROTAC SMARCA2 (BRM) degrading agent with a DC50 ranging between 10-100 nM (BRM) and over 1 μM (BRG1, also known as SMARCA2).

FHT-1204 is a potent inhibitor of SMARCA4 SMARCA2 ATPase (BRG1 and BRM) (IC50 ≤ 10 nM).

FHT-1015 is a potent SMARCA4 SMARCA2 ATPase (BRG1 and BRM) inhibitor with potential anticancer activity for the study of cancer and inflammation.

SMARCA2-IN-7 (compound 12) acts as a dual inhibitor for both BRM and BRG1 with IC50 values less than 0.005, exhibiting antitumor proliferation effects. It inhibits tumor proliferation in SKMEL5 cells lacking BRG1 with an AAC50 of 13 nM. Additionally, in H1299 cells, it suppresses cell proliferation activity of KRT880 with an AAC50 of 42 nM.

SMARCA2-IN-8 (Compound 13) is an orally effective inhibitor targeting the SWI SNF chromatin remodeling complexes SMARCA2 (also known as Brahma homolog, BRM) and SMARCA4 (also known as Brahma-related gene 1, BRG1), with IC50 values of 5 nM and 6 nM respectively. This compound inhibits the proliferation of SMARCA2-mutant SKMEL5 cancer cells with an AAC50 of 5 nM and downregulates the expression of the SMARCA2-dependent gene KRT80, showing an AAC50 of 10 nM. Additionally, SMARCA2-IN-8 demonstrates antitumor efficacy and favorable pharmacokinetic properties in mice.