brd3-bd2

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.

BY27, a potent and selective BET BD2 inhibitor (Ki: 3.1 nM) with anticancer activity, inhibits BD1 BD2 of BRD2, BRD3, BRD4, and BRDT, and suppresses tumor growth.

ABBV-744 is a BDII-selective BET bromodomain inhibitor that inhibits BRD2 3 4. It is used in the research on inflammatory diseases, cancer, and AIDS.

MS402 is a novel BD1-selective BET BrD inhibitor.

INCB054329, a structurally distinct bromodomain and extraterminal domain (BET) inhibitor, inhibits BRD2-BD1, BRD2-BD2, BRD3-BD1, BRD3-BD2, BRD4-BD1, BRD4-BD2, BRDT-BD1 and BRDT-BD2 with IC50 values of 44 nM, 5 nM, 9 nM, 1 nM, 28 nM, 3 nM, 119 nM and 63 nM respectively.

RVX-297 is a BD2 selective inhibitor of BET bromodomains. RVX-297 preferentially binds to the BD2 domains of the BET bromodomain and Extra Terminal (BET) family of protein.

GXF-111, a proteolysis targeting chimera (PROTAC) molecule, efficiently induces the selective degradation of the BRD3 and BRD4-L proteins. It exhibits high binding affinities to both BRD3 BD1 and BRD3 BD2, with K i values of 11.97 nM and 2.35 nM, respectively. This compound is utilized in cancer research [1].

BRD4 Inhibitor-28 (Compound 18), an orally active molecule, selectively inhibits the bromodomains of BRD4 (BRD4-BD1 and BRD4-BD2) with IC50 values of 15 and 55 nM, respectively. It also demonstrates inhibition of BRD2-BD1, BRD3-BD1, and BRDT-BD1 with IC50 values of 19, 25, and 68 nM, respectively. Furthermore, this compound exhibits anti-melanoma activity [1].

XY153 (compound 8l) is a BD2-selective BET inhibitor that binds BRD4 BD2 with an IC50 of 0.79 nM, BRD3 BD2 with an IC50 of 5.31 nM, and BRD2 BD2 with an IC50 of 5.09 nM. XY153 is used to study acute myeloid leukaemia and cancer.

GSK046 (iBET-BD2) is a potent, selective, and orally active BD2 bromodomain inhibitor of the BET proteins, with IC50 values of 264 nM [BRD2 BD2], 98 nM [BRD3 BD2], 49 nM [BRD4 BD2], and 214 nM [BRDT BD2], respectively. It exhibits immunomodulatory activity.

BET-IN-27 (compound 6C) is an orally active BET inhibitor with IC50 values of 3.3 nM (BRD4-BD2), 3.4 nM (BRD4-BD1), 4.1 nM (BRD2-BD1), 20.4 nM (BRD3-BD1), and 42.0 nM (BRDT-BD1). It also exhibits antiproliferative activity.

PLX51107 is a potent and selective BET inhibitor with Kds of 1.6, 2.1, 1.7, and 5 nM for BRD2-BD1, BRD3-BD1, BRD4-BD1, and BRDT-BD1, respectively.

BRD4 degrader AT1 is a highly selective Brd4 degrader based on PROTAC technology, with a Kd of 44 nM for Brd4BD2 in cells.

I-BET282E is a pan-inhibitor of eight BET bromodomains and shows selectivity for other representative bromodomain-containing proteins. It can act on eight BRD2 (BD1 BD2), BRD2 (BD1 BD), BRD3 (BD1 BD), and BRD4 (BD1 BD), with their pIC50 values ranging from 6.4 to 7.7.

SJ46421, a PROTAC protein degrader derived from (+)-JQ-1, targets KLHDC2. It efficiently forms a stable ternary complex with KLHDC2, exhibiting an IC50 of 7.8 nM. Furthermore, SJ46421 promotes the polyubiquitination of the BD2 domain of BRD2, BRD3, or BRD4.

GSK973 is a highly selective and orally bioavailable inhibitor that targets the second bromodomains (BD2s) of the BET family. It exhibits a pIC 50 of 7.8 and a pK d of 8.7 specifically for BRD4 BD2. Additionally, GSK973 demonstrates a remarkable selectivity of 1600-fold for BRD4 BD2 over BRD4 BD1. Moreover, it displays good potency against BRD2 BD2, BRD3 BD2, and BRDT BD2, with pIC 50 ranging from 7.4 to 7.8 and pK d ranging from 8.3 to 8.5.

PARP1 BRD4-IN-3 (compound HF4) is an effective inhibitor of BRD4 and PARP1, with IC50 values of 1210 nM and 2019 nM respectively. The compound exhibits antiproliferative activity, induces apoptosis (apoptosis) and cell cycle arrest at the G0 G1 phase. Additionally, PARP1 BRD4-IN-3 causes DNA damage and reduces the expression of the Rad51 protein, demonstrating anti-tumor activity.

GW841819X is an analogue of (+)-JQ1 and a novel inhibitor of BET bromodomains. GW841819X was a single enantiomer but of undefined chirality at the 4-position of the benzodiazepine ring3. GW841819X and JQ1 were recently discovered that bind to the acetyl-lysine binding pocket of BET bromodomains with Kd ranges from 50 to 370 nM [1]. GW841819X bounded to both the individual BD1 and BD2 domains with affinities of 46 and 52.5 nM, respectively. GW841819X-Brd3 interaction was estimated to be around 70 nM4. GW841819X displayed activity in vivo against NUT-midline carcinoma, multiple myeloma, mixed-lineage leukemia, and acute myeloid leukemia1. It also potent induced the ApoA1 reporter gene with an EC50 of 440 nM. It had very little effect on LDL-R luciferase activity at the concentrations at which it induces ApoA1 expression, suggesting that the effect is indeed specific3. GW841819X competed directly with GATA1 site for BD1 binding and also specifically blocked the interaction between Brd3 and acetylated GATA14. Recent findings reported that GW841819X are chose as an interest compound to further develop into potential drugs against diseases including cancer, HIV infection and heart disease2.

HJB97 is used for the design of potential PROTAC BET degrader. It also has antitumor activity. HJB97 is a high-affinity inhibitor of BET (Kis: 0.9 nM (BRD2 BD1), 0.27 nM (BRD2 BD2), 0.18 nM (BRD3 BD1), 0.21 nM (BRD3 BD2), 0.5 nM (BRD4 BD1), 1.0 nM (BRD4 BD2), respectively).

GS-626510 is an orally bioavailable inhibitor of BET family bromodomains (Kd: 0.59-3.2 nM for BRD2 3 4; IC50: 83 nM and 78 nM for BD1 and BD2).

BET BD2-IN-1 (compound 45) is a potent and selective BET BD2 inhibitor with an IC50 value of 1.6 nM. It suppresses Th17 cell differentiation by reducing the activation of STAT3 and NF-κB, making it relevant for psoriasis and inflammatory bowel disease (IBD) research [1].

XY221 (Compound 16o) selectively inhibits BRD4 BD2 with an IC50 of 5.8 nM. It demonstrates high selectivity for pan-BD2 and BRD4 BD2 domains, being 667 times more selective than for BRD4 BD1, and 9-32 times more selective than for BRD2 3 T BD2. XY221 can induce apoptosis in MV4-11 cells and exhibits anti-cancer activity.