brd4 in 2

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

BRD4 degrader-2 (Compound JP-2-197) is a covalent and monovalent molecule glue-type BRD4 degrader. It targets RNF126 (E3 ligase) to degrade both long and short isoforms of BRD4 in cells.

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

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.

PROTAC BRD4 Degrader-2 is an efficacious degrader of PROTAC BRD4(BRD4 BD1,IC50 of 14.2 nM).

PROTAC BRD2/BRD4 degrader-1 (compound 15) is a potent, selective degrader of BET proteins BRD4 and BRD2, achieving rapid, reversible, and unexpectedly selective elimination compared to BRD3. It effectively suppresses solid tumors with minimal cytotoxic effects and comprises a BET inhibitor, a connecting linker, and thalidomide as the ligand for cereblon (CRBN)/cullin 4A[1].

BRD4/FKBP12 degrader-2 (a1d) is a BRD4/FKBP12 degrader with anticancer activity.

PROTACFLT3/JAK2/BRD4 Degrader-1 is a PROTAC degrader targeting FLT3, JAK2, and BRD4, with DC50 values of 5.23 nM, 0.678 nM, and 1.17 nM, respectively. It exhibits potent antiproliferative activity against MV4;11 cells (IC50= 0.79 nM) and FLT3-mutated Ba/F3 cells. Additionally, PROTACFLT3/JAK2/BRD4 Degrader-1 induces apoptosis in MV4;11 cells and demonstrates significant antitumor efficacy in an MV4;11 xenograft model established in NOD SCID mice. This compound is applicable for research in acute myeloid leukemia (AML).

BRD4/CK2-IN-1 is a small molecule inhibitor targeting BRD4 and CK2, with an IC50 of 180nM for BRD4 and 230nM for CK2. It inhibits the proliferation of MDA-MB-231 and MDA-MB-468 cells, inducing apoptosis and autophagy-related cell death. It can be used in triple-negative breast cancer research.

PROTAC BRD4 Ligand-2 Hydrochloride serves as a ligand targeting the BRD4 protein, specifically designed for use with PROTAC CFT-2718.

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].

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.

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.

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 complex comprising a cereblon ligand and linker, suitable for synthesising PROTACs and click chemistry reactions.

(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.

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.

NB512 (compound 39a) is a dual inhibitor targeting both BET and HDAC, exhibiting high affinity for the BRD4 bromodomain and HDAC1/2, with EC50 values ranging from 100 to 400 nM. It demonstrates antiproliferative activity in cancer cell lines PaTu8988T and NMC.

FKBP12 ligand-2 (compound d) is a high-affinity ligand that targets FKBP12. This compound is utilized to selectively enhance the binding of heterobifunctional molecules to BRD4, facilitating the intracellular accumulation of drugs through the "CellTrap" effect. It forms a ternary complex of FKBP12-ligand-BRD4, which inhibits BRD4, suppresses the expression of BRD4 target genes such as MYC, and induces tumor cell death. FKBP12 ligand-2 is applicable in selective cancer research based on the differential levels of presenter proteins within cells.

4-[(1E)-2-Nitroethenyl]benzoic acid functions as an E3 ligase ligand and is utilized in the synthesis of PROTAC BRD4 Degrader-38.

JP-2-196 hydrochloride is a covalent molecular glue degrader that specifically targets RNF126. It facilitates the formation of a ternary complex between RNF126 and target proteins (e.g., BRD4, AR-V7), promoting their ubiquitination and proteasomal degradation. JP-2-196 hydrochloride is being explored for potential applications in cancer research, such as prostate cancer and leukemia.

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)