Epigenetic Reader Domain Inhibitor

(+)-JQ1 PA is a derivative of the Bromodomain and extra-terminal (BET) inhibitor JQ1, with an IC₅₀ of 10.4 nM. (+)-JQ1 PA is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.

GSK2801, a chemical probe, is a potent, selective, orally active and cell active acetyl-lysine competitive BAZ2A and BAZ2B bromodomains inhibitor with K_d values of 136 nM and 257 nM, respectively. GSK2801 shows >50-fold selectivity for BAZ2A/B over BRD4.

E-7386 is an orally active CBP/beta-catenin modulator.

GSK761 is a selective inhibitor of speckled 140 kDa (SP140) with an IC₅₀ value of 77.79 nM. GSK761 reduces monocyte-to-inflammatory macrophage differentiation and lipopolysaccharide (LPS)-induced inflammatory activation. GSK761 induces the production of CD206⁺ regulatory macrophages by inhibiting SP140.

BMS-986158 is a potent BET inhibitor with IC₅₀s of 6.6 and 5 nM in NCI-H211 small cell lung cancer (SCLC) cells and MDA-MB231 triple negative breast cancer (TNBC) cells, respectively.

Zefamenib (BN-104) is an effective selective brain membrane protein inhibitor with oral activity, and it's also a Menin inhibitor, it can block the Menin-MLL interaction and leads to the degradation of Menin protein. Zefamenib is a weak hERG inhibitor, with an IC₅₀ greater than 100 μM. Zefamenib has anti-tumor activity and can be used in cancer research, such as for acute myeloid leukemia.

IACS-9571 (ASIS-P040) hydrochloride is a potent and selective inhibitor of TRIM24 and BRPF1, with an IC₅₀ of 8 nM for TRIM24, and K_ds of 31 nM and 14 nM for TRIM24 and BRPF1, respectively.

Enzomenib (DSP-5336) is an orally active Menin inhibitor (IC₅₀=1.4 nM, K_d=6.0 nM). Enzomenib disrupts the interaction between Menin and KMT2A/MLL fusion proteins, specifically inhibits the expression of leukemia driver genes such as HOX/MEIS1, and upregulates ITGAM. Enzomenib effectively induces cell differentiation, inhibits tumor cell proliferation, and suppresses primitive cell colony formation. Enzomenib reduces disease burden and prolongs survival, but causes adverse reactions including differentiation syndrome and QTc interval prolongation. Enzomenib is used for research on relapsed/refractory acute myeloid leukemia, acute lymphoblastic leukemia, and other hematologic malignancies with mixed lineage leukemia (MLL) rearrangements or NPM1 mutations.

(R)-(-)-JQ1 Enantiomer is the stereoisomer of (+)-JQ1. (+)-JQ1 potently decreases expression of both BRD4 target genes, whereas (R)-(-)-JQ1 Enantiomer has no effect.

PLX51107 is a potent and selective BET inhibitor, with K_ds of 1.6, 2.1, 1.7, and 5 nM for BD1 and 5.9, 6.2, 6.1, and 120 nM for BD2 of BRD2, BRD3, BRD4, and BRDT, respectively; PLX51107 also interacts with the bromodomains of CBP and EP300 (K_d, in the 100 nM range).

MI-3454 is an orally active, highly potent and selective menin-MLL1 interaction inhibitor with an IC₅₀ of 0.51 nM. MI-3454 inhibits proliferation, induces differentiation and complete remission or regression of leukemia in mouse models of MLL1-rearranged or NPM1-mutated leukemia through downregulation of key genes involved in leukemogenesis.

AZD5153 6-Hydroxy-2-naphthoic acid is the 6-Hydroxy-2-naphthoic acid of AZD5153. AZD5153 is a potent, selective, and orally available BET/BRD4 bromodomain inhibitor; disrupts BRD4 with an IC₅₀ of 1.7 nM.

Biotinylated-JQ1 (Biotin-JQ1) is a biotinylated derivative of JQ1 with high affinity for the bromodomain of BRD4. Biotinylated-JQ1 inhibits MM1.S multiple myeloma cells proliferation with the EC₅₀ of 0.4 μM.

Hexamethylene bisacetamide (HMBA) is a differentiation inducer and selective bromine domain inhibitor that can differentiate across the blood-brain barrier. Hexamethylene bisacetamide can induce tumor cell differentiation and inhibit cell proliferation, showing antitumor activity. Hexamethylene bisacetamide induces apoptosis by Notch1, Bcl-2 and p53 signaling pathways. In addition, Hexamethylene bisacetamide improves the obesity phenotype of mice.

CPI-203 is a novel potent, selective and cell permeable inhibitor of BET bromodomain, with an IC₅₀ value of appr 37 nM (BRD4 α-screen assay).

NHWD-870 is a potent, orally active and selective BET family bromodomain inhibitor and only binds bromodomains of BRD2, BRD3, BRD4 (IC₅₀=2.7 nM), and BRDT. NHWD-870 has potent tumor suppressive efficacies and suppresses cancer cell-macrophage interaction. NHWD-870 increases tumor apoptosis and inhibits tumor proliferation.

PKI 14-22 amide, myristoylated TFA is a selective, cAMP-dependent, competitive PKA inhibitor with K_i=~36 nM. The myristoylation modification of PKI 14-22 amide, myristoylated TFA makes it more permeable to cell membranes and blood-brain barriers than the precursor molecule. PKI 14-22 amide, myristoylated TFA can block the phosphorylation of cAMP-dependent downstream targets (such as CREB). PKI 14-22 amide, myristoylated TFA can prevent the development of analgesic tolerance in mice, and also inhibits protein translation and negative-strand RNA synthesis of Zika virus. PKI 14-22 amide, myristoylated TFA can be used in research fields such as opioid tolerance mechanisms and antiviral drugs.

Amredobresib (BI894999) is an orally active BET inhibitor. Amredobresib inhibits the binding of BRD4-BD1 and BRD4-BD2 bromodomains to acetylated histones with IC₅₀ values of 5 nM and 41 nM, respectively. Amredobresib exhibits anticancer activity against acute myeloid leukemia (AML) and NUT cancer.

TDI-11055 is a selective and orally active eleven-nineteen leukemia (ENL) inhibitor, which displaces ENL from chromatin by blocking its YEATS domain interaction with acylated histones. TDI-11055 inhibits ENL and AF9 YEATS domains with IC₅₀ values of 50 nM and 70 nM, respectively, and no activity against GAS41 or YEATS2. TDI-11055 decreases chromatin occupancy of ENL-associated complexes, impairs transcription elongation, suppresses key oncogenic gene expression programs, and induces differentiation. TDI-11055 can be used for the research of acute myeloid leukemia.

GSK620, a chemical probe, is a potent and orally active pan-BD2 inhibitor with excellent broad selectivity, developability and in vivo oral pharmacokinetics. GSK620 is highly selective for the BET-BD2 family of proteins, with >200-fold selectivity over all other bromodomains. GSK620 shows an anti-inflammatory phenotype in human whole blood.