swi/snf

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).

Compound I-291, also known as PROTAC SMARCA2 4-degrader-30, targets the catalytic subunits of the SWI SNF complex, specifically SMARCA2 and SMARCA4. It effectively degrades SMARCA2 in A549 and MV411 cells, as well as SMARCA4 in MV411 cells, with a degradation concentration (DC50) of less than 100 nM.

PROTAC SMARCA2 4-degrader-29 (Compound I-279) serves as a degrader for the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. In A549 cells, this compound effectively degrades SMARCA2 with a DC50 value of less than 100 nM, and similarly degrades SMARCA4 in MV411 cells with a DC50 under 100 nM.

HH-2853 is a potent inhibitor targeting EZH1 2, demonstrating significant antitumor activity. Its IC50 values for both wild-type and mutant EZH2 range from 2.21-5.36 nM, comparable to tazemetostat. HH-2853 is more effective against EZH1, with an IC50 of 9.26 nM, notably lower than tazemetostat's 58.43 nM. However, at concentrations up to 10 μM, it exhibits minimal inhibitory activity on 36 types of histone-modifying enzymes. On the cellular level, HH-2853 effectively inhibits mono-, di-, and tri-methylation of H3K27 in various cancer cell lines with wild-type or mutant EZH2, without affecting other methylation types on histone H3 at concentrations up to 10 μM. Additionally, HH-2853 significantly reduces cell viability in multiple cancer cell lines carrying EZH2 GOF mutations or SWI SNF complex alterations, and demonstrates superior antitumor effects compared to tazemetostat in several tumor xenograft models at equivalent doses.

Seclidemstat mesylate (SP-2577) is a highly effective and reversible inhibitor of KDM1A (LSD1), with a Ki of 31 nM and an IC50 of 13 nM. It shows promising potential in enhancing antitumor immunity in switch sucrose nonfermentable (SWI SNF) complex mutated ovarian cancer and exhibits inhibitory effects on virus production, viral DNA replication, and late gene expression. Additionally, seclidemstat mesylate is a valuable tool for studying Ewing Sarcoma in research settings.

Seclidemstat (SP-2577) is an effective LSD1 inhibitor, with a mean IC50 of 127 nM.

PROTAC SMARCA2 degrader-3, a degrader targeting the SWI SNF ATPase subunits specifically SMARCA2, exhibits anticancer properties (WO2023244764A1; Compound 153) [1].

PROTAC SMARCA2 4-degrader-8 (Compound I-502) is a PROTAC degrader targeting the catalytic subunit SMARCA of the SWI SNF complex. It degrades SMARCA2 in A549 and MV411 cells with a DC50 of <100 nM and SMARCA4 in MV411 cells, also exhibiting a DC50 of <100 nM.

PROTAC SMARCA2 4-degrader-4 (Compound I-434) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It efficiently degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM and degrades SMARCA4 in MV411 cells, also with a DC50 of less than 100 nM.

PROTACSMARCA2 degrader-5 (Compound I-425) functions as a PROTAC degrader targeting the catalytic subunit SMARCA2 of the SWI SNF complex. It effectively degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM, and also degrades SMARCA4 in MV411, exhibiting a DC50 ranging from 100-500 nM.

PROTAC SMARCA2 4-degrader-20 (Compound I-405) is a PROTAC degrader targeting the catalytic subunit SMARCA2 in the SWI SNF complex. It degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM. Additionally, it degrades SMARCA4 in MV411 with a DC50 ranging between 100 to 500 nM.

PROTAC SMARCA2 4-degrader-5 (Compound I-437) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM and degrades SMARCA4 in MV411 with a DC50 ranging from 100 to 500 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.

PROTAC SMARCA2 4-degrader-19 (Compound I-412) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM, and it degrades SMARCA4 in MV411 with a DC50 also under 100 nM.

PROTAC SMARCA2 4-degrader-9 (Compound I-503) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It effectively degrades SMARCA2 in MV411 and A549 cells, with a DC50 of less than 100 nM, and degrades SMARCA4 in MV411 with a similar DC50.

SMARCA2-IN-4 (Compound 26) is an inhibitor of the SWI SNF chromatin remodeling complex SMARCA, specifically targeting its bromodomain. This compound exhibits high affinity for PB1(5), SMARCA2B, and SMARCA4, with dissociation constants (Kd) of 124, 262, and 417 nM, respectively.

SMARCA2-IN-1 (Compound I-19) serves as an inhibitor of the SWI SNF chromatin remodeling complex SMARCA2, exhibiting an IC50 value greater than 1000 nM in H1299 cells.

PROTACSMARCA2 degrader-7 (Compound I-428) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. In MV411, it achieves degradation of SMARCA2 and SMARCA4 with DC50 values of <100 nM and 100-500 nM, respectively.

PROTAC SMARCA2 4-degrader-17 (Compound I-345) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It degrades SMARCA2 in A549 cells with a DC50<100 nM and SMARCA4 in MV411 cells, also demonstrating a DC50<100 nM.

DCSM06 is an inhibitor of the bromodomain of the SMARCA2 subunit within the SWI SNF chromatin remodeling complex, displaying an IC50 of 9.7 μM.

PROTACSMARCA2 degrader-4 (Compound I-424) is a PROTAC degradative agent targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It effectively degrades SMARCA2 in MV411 and A549 cell lines with a DC50 of less than 100 nM and degrades SMARCA4 in MV411 with a DC50 exceeding 1 μM.

PROTAC SMARCA2 4-degrader-15 (Compound I-335) is a PROTAC degrader designed for the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It degrades SMARCA2 in A549 cells with a DC50 of less than 100 nM; similarly, it degrades SMARCA4 in MV411 cells, also with a DC50 of less than 100 nM.

PROTAC SMARCA2 4-degrader-18 (Compound I-348) is a PROTAC degrader targeting the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It effectively degrades SMARCA2 in A549 cells with a DC50 value of less than 100 nM and similarly degrades SMARCA4 in MV411 cells, also with a DC50 of less than 100 nM.

PROTAC SMARCA2 4-degrader-31 (Compound I-280) serves as a degrader for the catalytic subunits SMARCA2 and SMARCA4 of the SWI SNF complex. It effectively degrades SMARCA2 in A549 cells and SMARCA4 in MV411 cells, both with a degradation concentration (DC50) of less than 100 nM.