BRD4-IN-2

BRD4-IN-2 is a bromodomain BRD4 inhibitor with an IC50 value of 9.9 nM.

PARP1 BRD4-IN-2 is a potent and selective inhibitor of PARP1 (IC50: 197 nM) and BRD4 (IC50: 238 nM), which inhibits DNA damage repair, blocks the G0 G1 cell cycle transition, and induces apoptosis. PARP1 BRD4-IN-2 exhibits antitumor effects in the MDA-MB-468 mouse xenograft tumor model and is used to study triple-negative breast cancer (TNBC).

PLK1 BRD4-IN-2 (compound 15), an analog of BI-2536, simultaneously inhibits both Polo-like kinase 1 (PLK1 IC 50 = 40 nM) and BRD4 bromodomain (BRD4-BD1 IC 50 = 28 nM) as a dual inhibitor [1].

BRD4-BD1-IN-2 is a selective and potent BRD4-BD1 inhibitor with an IC50 value of 2.51 µM, exhibiting 20-fold greater inhibitory activity against BRD4-BD1 compared to BRD4-BD2. [BRD4-BD1-IN-2] is applicable for research in cardiovascular and cancer-related diseases.

BRD4-BD1 2-IN-1 is a highly effective inhibitor of BRD4, targeting the BRD4 BD-1 and BD-2 domains with IC50 values of <100 nM each (US20150148375A1, compound 5) [1].

BRD4-BD1 2-IN-2 is a potent inhibitor of BRD4-BD2, effective on both BRD4 BD2 (IC50 < 0.5 nM) and BRD4 BD1 (IC50 < 300 nM).

BRD4 D1-IN-2 (compound 26) is a selective and potent inhibitor of BRD4 D1, exhibiting an IC50 value of less than 0.092 μM and a 15 nM affinity for BRD4 D1, with over 500-fold selectivity for BRD2 D1 and BRD4 D2.

CF53 is a highly potent, selective, and orally active inhibitor of BET protein, with a Ki of <1 nM, Kd of 2.2 nM, and an IC50 of 2 nM for BRD4 BD1. CF53 binds to both the BD1 and BD2 domains of BRD2, BRD3, BRD4, and BRDT BET proteins with high affinities, being very selective over non-BET bromodomain-containing proteins. CF53 exhibits potent anti-tumor activity both in vitro and in vivo.

(R)-(-)-JQ1 Enantiomer is the stereoisomer of (+)-JQ1, a BET bromodomain inhibitor, which acts on BRD4(1 2) with IC50 values of 77 nM and 33 nM in a cell-free assay.

BET-IN-2 is a BET inhibitor with an IC50 of 52 nM for BRD4-BD1.

Lenalidomide-PEG1-azide is an E3 ligase ligand-linker conjugate that incorporates the cereblon ligand based on Lenalidomide and a linker. It is designed for use in the development of PROTAC BRD4 Degrader-2[1].

HDAC3 BRD4-IN-1 (compound 26n) is an inhibitor of HDAC3 BRD4, exhibiting an IC50 of 8 nM for HDAC3, while its IC50 values for HDAC1 and HDAC2 are 220 nM and 120 nM, respectively. It displays anti-tumor and anti-proliferative effects by upregulating Ac-H3 and downregulating c-Myc. The half-life of HDAC3 BRD4-IN-1 in human liver microsomes is 29.36 minutes.

AZD5153 6-Hydroxy-2-naphthoic acid (AZD5153) is a potent triazolopyridazine-based Bromodomain (BRD4) and Extraterminal (BET) inhibitor utilized in cancer treatments.

TW9 is a dual inhibitor of bromodomain 2 (BD2) in bromodomain-containing protein 4 (BRD4) and histone deacetylase 1 (HDAC1; IC50s = 0.074 and 0.29 μM, respectively).1It is selective for BD2 over BD1 in BRD4 (IC50= 0.72 μM) and for HDAC1 over HDAC2 (IC50= 2.5 μM). TW9 (50 nM) induces apoptosis in, and inhibits proliferation of, MIA PaCa-2 pancreatic cancer cells. It induces cell cycle arrest at the G1phase in HPAC pancreatic cancer cells when used at a concentration of 2 μM. TW9 acts synergistically with gemcitabine to reduce the viability of HPAC cells. 1.Zhang, X., Zegar, T., Weiser, T., et al.Characterization of a dual BET HDAC inhibitor for treatment of pancreatic ductal adenocarcinomaInt. J. Cancer147(10)2847-2861(2020)

PROTAC BRD4 Degrader-8 is a potent BRD4 inhibitor with IC50 values of 1.1 nM and 1.4 nM for BRD4 BD1 and BD2, respectively, effectively degrading the BRD4 protein in PC3 prostate cancer cells[1].

CAY17c is an inhibitor of bromodomain-containing protein 4 (BRD4; IC50= 0.71 μM), as well as class I histone deacetylases (HDACs; IC50s = 0.046, 0.058, 0.075, and 0.167 μM for HDAC1, -2, -3, and -8, respectively) and class IIb HDACs (IC50s = 0.073 and 0.923 μM for HDAC6 and HDAC10, respectively).1It is selective for these enzymes over BRD2, -3, and -T (IC50s = >20 μM for all), as well as over HDAC4, -5, -7, -9, and -11 (IC50s = >10 μM for all). CAY17c inhibits the proliferation of HCT116, SW620, and DLD-1 colorectal cancer cells (IC50s = 0.45, 1.78, and 2.11 μM, respectively), as well as induces apoptosis and autophagy in HCT116 cells. It reduces tumor growth in an HCT116 mouse xenograft model when administered at doses of 15 and 30 mg/kg. 1.Pan, Z., Li, X., Wang, Y., et al.Discovery of thieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as bromodomain-containing protein 4/histone deacetylase dual inhibitors induce autophagic cell death in colorectal carcinoma cellsJ. Med. Chem.63(7)3678-3700(2020)

PROTAC BRD4 ligand-2 is a ligand for the target BRD4 protein used in the development of PROTAC CFT-2718.

BRD4 Inhibitor-15 (compound 13) is a highly potent and specific BRD4 inhibitor with an IC50 of 18 nM, inducing apoptosis in 22RV1 cells by regulating Bcl-2 Bax proteins and activating caspase-3 signaling, and down-regulating c-Myc levels, making it valuable for prostate cancer research [1].

PROTAC BRD3 BRD4-L degrader-2, a PROTAC molecule, selectively degrades cellular BRD3 and BRD4-L with K i values of 16.91 and 2.8 nM, respectively, and exhibits robust antitumor activity in mouse xenograft models, serving as a research tool for cancer [1].

This novel compound is an orally bioavailable antagonist of P2X3 P2X2 3 receptors, exhibiting potent activity with a pIC50 of 8 in both human and rat, and a pIC50 of 7.3 specifically for the human P2X2 3 receptor. It demonstrates high brain penetration, evidenced by a brain to plasma ratio of 6, and effectively blocks agonist-evoked intracellular Ca2+ flux and inward currents within the nanomolar range (10 nM to 1 µM) in cell lines that express human P2X3 and P2X2 3 receptors recombinantly. The compound also shows favorable pharmacokinetic properties, with a half-life (t1 2) of 1.63 hours and a time to reach maximum concentration (Tmax) of 30 minutes.

PROTAC BRD4 Degrader-5-CO-PEG3-N3 (Compound 2) is a PROTAC-linker conjugate utilized in PAC, comprising the BRD4 degrader GNE-987 connected with a 3-PEG linker. This compound serves as a click chemistry reagent, featuring an Azide group capable of undergoing copper-catalyzed azide-alkyne cycloaddition reactions (CuAAc) with molecules containing an Alkyne group. Additionally, it can participate in strain-promoted alkyne-azide cycloaddition reactions (SPAAC) with molecules that possess DBCO or BCN groups.