SWI/SNF Complex Inhibitor

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.

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.

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.

PFI-3, a chemical probe, is a selective, potent and cell-permeable SMARCA2/4 bromodomain inhibitor with a K_d of 89 nM.

ACBI2 is a highly potent and orally active VHL PROTAC SMARCA2 degrader (EC₅₀: 7 nM), which selectively degrades SMARCA2 with a DC₅₀ value of 1 nM in RKO cells. ACBI2 can be used in the research of lung cancer.

FHT-1015 is a selective SMARCA4 (IC₅₀ = 4 nM) and SMARCA2 (IC₅₀ = 5 nM) (also known as BRG1 and BRM) inhibitor. FH-1015 is an allosteric inhibitor that causes conformation change in the BRG1/BRM protein upon interaction with an allosteric site, inhibiting ATPase activity. FH-1015 interferes with tumor cell growth and migration. FH-1015 can be studied in research for uveal melanoma and hematologic cancer.

SGC-SMARCA-BRDVIII, a chemical probe, is a potent and selective inhibitor of SMARCA2/4 and PB1(5), with K_ds of 35 nM, 36 nM, and 13 nM, respectively. SGC-SMARCA-BRDVIII also inhibits PB1(2) and PB1(3), with K_ds of 3.7 and 2.0 μM, respectively. SGC-SMARCA-BRDVIII can block adipogenesis of 3T3-L1 murine fibroblasts.

GNE-064 (compound 5) is a selective, orally active and highly soluble inhibitor of SMARCA4, SMARCA2 and PBRM1 bromodomains 5. GNE-064 inhibits SMARCA4 with an IC₅₀ of 0.035 μM and inhibits SMARCA2 with an EC₅₀ of 0.10 μM. GNE-064 possess K_ds with 0.01, 0.016, 0.018 and 0.049 μM for SMARCA4, SMARCA2, PBRM1 bromodomains 5 and PBRM1 bromodomains 2, repectively. GNE-064 can be used as a chemical probe for the research of agent synthesis.

FHT-2344, a chemical probe, is a SMARCA4/SMARCA2 ATPase inhibitor with IC₅₀ values of 0.026 μM and 0.013 μM, respectively. FHT-2344 has anticancer activity.

BPTF-IN-BZ1, a BPTF inhibitor, possesses a high potency (K_d = 6.3 nM).

PBRM1-BD2-IN-5 is a potent PBRM1 Bromodomain inhibitor with K_d values of 1.5 μM and 3.9 μM for PBRM1-BD2 and PBRM1-BD5, respectively, and an IC₅₀ value of 0.26 μM for PBRM1-BD2. PBRM1-BD2-IN-5 reduces the binding of full-length PBRM1 within the PBAF complex in cell lysates to acetylated histone peptide. PBRM1-BD2-IN-5 can be used to research anticancer.

BRM/BRG1 ATP Inhibitor-2 is a BRG1/BRM ATPase inhibitor for the research of BAF-related disorders.

FHT-1204 is a potent SMARCA4/SMARCA2 ATPase (BRG1 and BRM) inhibitor with IC₅₀s of ≤10 nM (WO2020160180A1; compound 70).

DC-BPi-11 hydrochloride is an inhibitor of bromodomain PHD finger transcription factor (BPTF), with an IC₅₀ value of 698 nM. DC-BPi-11 hydrochloride shows remarkable inhibition against leukemia cell proliferation.

IV-255 is a selective small molecule inhibitor of the BRG1 bromodomain. IV-255 increases the extent of DNA damage induced by Temozolomide (HY-17364) and Bleomycin (HY-108345). IV-255 inhibits the invasiveness of GBM cells. IV-255 enhances Temozolomide-induced cell death and the apoptosis-inducing activity of Temozolomide.

PBRM1-BD2-IN-8 (compound 34) is a potent PBRM1 Bromodomain inhibitor (PBRM1-BD2 K_d=4.4 μM, PBRM1-BD2 IC₅₀=0.16 μM; PBRM1-BD5 K_d=25 μM). PBRM1-BD2-IN-8 shows anti-cancer activity.

SMARCA2/4-IN-2 is a PROTAC target protein ligand (Ligands for Target Protein for PROTACs). SMARCA2/4-IN-2 can be used for synthesis PROTAC SMARCA2/4-degrader-5 (HY-159456).

PBRM1-BD2-IN-2 is a selective and cell-active polybromo-1 (PBRM1) bromodomain inhibitor. PBRM1-BD2-IN-2 has binding affinity and inhibitory activity for PBRM1-BD2 with K_d and IC₅₀ values of 9.3 μM and 1.0 μM, respectively. PBRM1-BD2-IN-2 can be used for the research of cancer.

DC-BPi-03 is a potent BPTF-BRD inhibitor with an IC₅₀ of 698.3 nM and a K_d of 2.81 μM.

SMARCA2-IN-1 (Compound I-19) is an inhibitor for SWI/SNF chromatin remodeling complexe SMARCA2 with IC₅₀ >1000 nM in H1299.