Epigenetic Reader Domain Inhibitor

PFI-1, a chemical probe, is a selective BET (bromodomain-containing protein) inhibitor for BRD4 with IC₅₀ of 0.22 μM in a cell-free assay.

OF-1, a chemical probe, is a potent pan-BRPF bromodomain (BRD) inhibitor, with IC₅₀ values of 270 nM, 1.2 μM for TRIM24 and BRPF1B, respectively.

GSK1324726A is a novel, potent, and selective inhibitor of BET proteins with high affinity to BRD2 (IC₅₀=41 nM), BRD3 (IC₅₀=31 nM), and BRD4 (IC₅₀=22 nM).

BRD7-IN-2 (compound 2-77) is a potent inhibitor of bromodomain-containing protein 7 (BRD7), targeting to prostate cancer cells. BRD7-IN-2 is selective for BRD7 rather than BRD9, with IC50s of 5.4 μM, and >300 μM, respectively.

SF2523 is a highly selective and potent inhibitor of PI3K with IC₅₀s of 34 nM, 158 nM, 9 nM, 241 nM and 280 nM for PI3Kα, PI3Kγ, DNA-PK, BRD4 and mTOR, respectively.

MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC₅₀ of 21 nM.

GSK-5959 is a potent, selective and cell permeable BRPF1 bromodomain inhibitor with an IC₅₀ of ~ 80 nM.

GSK973, a chemical probe, is a highly selective, orally bioavailable inhibitor of the BD2s (second bromodomains) of the BET family, with a pIC₅₀ of 7.8 and a pK_d of 8.7 for BRD4 BD2. GSK973 displays a 1600-fold selectivity for BRD4 BD2 over BRD4 BD1. GSK973 shows good potency against BRD2 BD2, BRD3 BD2, and BRDT BD2 (pIC₅₀=7.4~7.8; pK_d=8.3~8.5).

KMI169 is a potent and selective inhibitor targeting lysine methyl-transferase (KMT9) (IC₅₀ = 0.05 μM, K_d = 0.025 μM). KMI169 functions as a bi-substrate inhibitor targeting the cofactor S-5’-adenosyl-L-methionine (SAM) and substrate binding pockets of KMT9. KMI169 can downregulate target genes involved in cell cycle regulation and impair proliferation of tumor cells by inhibiting KMT9. KMI169 is a valuable tool to probe cellular KMT9 functions and can be research for combating diseases including prostate, lung, colon, and invasive bladder cancer.

MS436 is a new class of bromodomain inhibitor, exhibits potent affinity of an estimated K_i=30-50 nM for the BRD4 BrD1 and a 10-fold selectivity over the BrD2.

VTP50469 fumarate is a potent, highly selective and orally active Menin-MLL interaction inhibitor with a K_i of 104 pM. VTP50469 fumarate has potently anti-leukemia activity.

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.

INCB054329 is a potent BET inhibitor.

BETd-260 (ZBC 260) is a BET PROTAC degrader. BETd-260 recruits BRD2, BRD3, and BRD4 to the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex, driving cereblon-, proteasome-, and NEDD8-activating enzyme-dependent ubiquitination and degradation, with a DC50 of approximately 30-100 pM in RS4;11 cells. BETd-260 induces cancer cell apoptosis via endogenous signaling pathways, regulates the expression of the Bcl-2 family, inhibits the oncogene c-Myc, and reduces cell viability. BETd-260 suppresses tumor growth in mouse xenograft models with good biosafety. BETd-260 can be used in research related to acute leukemia, hepatocellular carcinoma, osteosarcoma, and triple-negative breast cancer.

LT052 is a highly selective BET BD1 inhibitor with an IC₅₀ of 87.7 nM. LT052 exhibits nanomolar BRD4 BD1 potency and 138-fold selectivity over BRD4 BD2 (IC₅₀=12.130 μM). LT052 has anti-inflammatory?activity and can be used for acute gout arthritis research.

ZL0454 is a potent and selective Bromodomain-containing protein 4 (BRD4) inhibitor with an IC₅₀ of 49 and 32 nM for BD1 and BD2.

LP99, an epigenetic probe, is a potent and selective inhibitor of the BRD7 and BRD9 bromodomains with a K_d of 99 nM against BRD9. LP99 disrupts the binding of BRD7 and BRD9 to chromatin in cells.

MT1 is a bivalent chemical probe of BET bromodomains, with an IC₅₀ of 0.789 nM for BRD4(1).

4-Chloro-N-methylpicolinamide (Compound 3) is a BAZ2A bromodomain inhibitor with a K_d of >500 μM. 4-Chloro-N-methylpicolinamide forms a weak hydrogen bond with the carbonyl oxygen of Pro1817. 4-Chloro-N-methylpicolinamide can be used in the research of invasive prostate cancer.

KPT-276 is an orally active and blood-brain barrier-penetrant selective XPO1/CRM1 inhibitor. KPT-276 blocks XPO1-mediated nuclear export function and promotes nuclear retention of various tumor suppressor proteins. KPT-276 induces apoptosis and G1 cell cycle arrest in tumor cells, and downregulates c-MYC, CDC25A, and BRD4. KPT-276 reduces immune cell proliferation through nuclear accumulation of cell cycle inhibitors, rescues TDP-43 cytoplasmic mislocalization, and restores axon growth and growth rate in mutant PFN1 motor neurons. KPT-276 maintains axonal cytoskeletal integrity and mitochondrial function, and inhibits tumor growth. KPT-276 can be used for research on glioblastoma, non-Hodgkin lymphoma, amyotrophic lateral sclerosis, multiple myeloma, and non-small cell lung cancer.