Epigenetic Reader Domain Inhibitor

MI-463 is a highly potent and orally bioavailable small molecule inhibitor of the menin-mLL interaction.

SR-0813 is a potent and selective ENL/AF9 YEATS domain inhibitor. SR-0813 has IC₅₀ and EC₅₀ values of 25 nM and 205 nM for ENL YEATS domain, respectively. SR-0813 has IC₅₀ and EC₅₀ values of 311 nM and 76 nM (CETSA) for AF9 YEATS domain, respectively. SR-0813 binds MAP3K19 with over 100-fold lower affinity (K_d=3.5 μM) than ENL YEATS (K_d=30 nM). SR-0813 can be used for the research of acute leukemia.

BAZ2-ICR is a potent, selective, cell active and orally active BAZ2A/B bromodomains inhibitor with IC₅₀s of 130 nM and 180 nM, and K_ds of 109 nM and 170 nM, respectively. BAZ2-ICR shows 10-15-fold selectivity for binding BAZ2A/B over CECR2 and >100-fold selectivity over all other bromodomains. BAZ2-ICR is an epigenetic chemical probe.

CC-90010 (compound 1) is a reversible and orally active BET inhibitor. CC-90010 is applied in the study for advanced solid tumors.

AZ13824374 is a potent and selective ATAD2 bromodomain inhibitor (pIC₅₀ of 6.9 in HCT116 cells). AZ13824374 disrupts chromatin interactions and gene transcription by binding to the acetyl-lysine binding site of the ATAD2 bromodomain. AZ13824374 has anticancer activity against breast cancer.

GSK6853, a chemical probe, is a potent and selective inhibitor of the BRPF1 bromodomain. GSK6853 shows excellent BRPF1 potency (pK_d = 9.5) and greater than 1600-fold selectivity over all other bromodomains.

Menin-MLL inhibitor MI-2 is a competitive and selective Menin-MLL interaction inhibitor with an IC₅₀ value of 446 nM and a K_i value of 158 nM. Menin-MLL inhibitor MI-2 downregulates the expression of target genes such as HOXA9 and MEIS1, inhibits proliferation of leukemia cells and induces apoptosis and differentiation. Menin-MLL inhibitor MI-2 is proming for rasearch of MLL-rearranged acute leukemias (e.g., AML, ALL).

MI-2-2 is a potent menin-MLL inhibitor. MI-2-2 binds to menin with low nanomolar affinity (K_d=22nM) and very effectively disrupts the bivalent protein-protein interaction between menin and MLL. MI-2-2 has specific and very pronounced activity in MLL leukemia cells, including inhibition of cell proliferation, down-regulation of Hoxa9 expression, and differentiation.

SGC-iMLLT is a first-in-class chemical probe and a potent, selective inhibitor of MLLT1/3-histone interactions with an IC₅₀ of 0.26 μM. SGC-iMLLT shows high binding activity towards MLLT1 YEATS domain (YD) and MLLT3 YD (AF9/YEATS3) with K_ds of 0.129 and 0.077 μM, respectively.

NI-57, a chemical probe, is an inhibitor of bromodomain and plant homeodomain finger-containing (BRPF) famlily of proteins, with IC₅₀s of 3.1, 46 and 140 nM for BRPF1, BRPF2 (BRD1) and BRPF3, respectively.

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.

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.

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.

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