brdt-bd1

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.

LT052 is a selective and efficient BET BD1 inhibitor with anti-inflammatory activity. It mediates the BRD4 NF-κB NLRP3 inflammatory signaling pathway and can be used in gout arthritis research.

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.

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].

GSK778 is a potent and selective inhibitor of BD1 bromodomain such as BRD2 BD1 (IC50s = 75 nM), BRD3 BD1 (IC50s = 41 nM), BRD4 BD1 (IC50s = 41 nM), and BRDT BD1 (IC50s = 143 nM). GSK778 inhibits proliferation, induces a cell cycle arrest and apoptosis.

BI01826025 (pArg-JQ1), a PROTAC degrader targeting the bromodomain 1 of BRDT (BRDT BD1), proves useful in exploring the regulatory impact of ClpC2 on the ClpC1P1P2 protease complex [1].

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.

SB-284851-BT is a chemical compound that serves as an inhibitor of BRD4, p38α, and BRDT, exhibiting varying degrees of affinity and inhibition for each. Specifically, it inhibits BRD4-BD1 with an IC50 value of 1.7 µM, p38α with a Kd of 0.47 nM, BRDT (1) with an IC50 value of 18 µM, and BRD4 (1) with an IC50 value of 3.7 µM. By targeting p38α, SB-284851-BT effectively reduces IL-8 production and, through inhibiting BRD4, down-regulates both the c-Myc and NF-κB gene pathways, crucial in cancer pathways. Additionally, SB-284851-BT is designed to combine with the bromine domain and extra terminal (BET) proteins.

N-Methyl-N′-[2-methyl-5-[[[1-methyl-3-(pyridin-4-yl)-1H-indazol-5-yl]carbonyl]amino]phenyl]terephthalamide showed weak affinity for BRDT-BD1 with IC50 values >10 μM.

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.

Compound 21, also known as PLK1 BRD4-IN-3, acts as a selective dual inhibitor targeting both bromodomain 4 (BRD4) and polo-like kinase 1 (PLK1). It effectively inhibits BRD4-BD1, PLK1, and BRDT-BD1, exhibiting IC50 values of 0.059, 0.127, and 0.245 μM, respectively.

GSK778 hydrochloride hydrochloride is a potent and selective BD1 bromodomain inhibitor of the BET proteins, with IC50s of 75 nM (BRD2 BD1), 41 nM (BRD3 BD1), 41 nM (BRD4 BD1), and 143 nM (BRDT BD1), respectively. GSK778 hydrochloride hydrochloride phenocopies the effects of pan-BET inhibitors in cancer models[1].

DDO-8958 is an orally active and selective BET BD1 inhibitor, exhibiting a KD of 5.6 nM for BRD4 BD1. It shows low nanomolar inhibitory activity across all BET BD1 bromodomains except for BRDT BD1. DDO-8958 inhibits tumor cell proliferation and migration, induces apoptosis and cell cycle arrest, and demonstrates antitumor activity.

N1-[5-[[[3-(4-Amino-2-methylphenyl)-1-methyl-1H-indazol-5-yl]carbonyl]amino]-2-methylphenyl]-N4-methyl-1,4-benzenedicarboxamide is a potent, selective second bromodomain (BD2) of BRDT and BRD4 inhibitor with IC50 of 7 and 25 nM, >1,000-fold and 300-fold selectivity over BRDT-BD1 and BRD4-BD1.

SRG-II-19F (dCym-JQ1), a BRDT BD1 (bromodomain1 of BRDT) degrader, is utilized to examine the regulatory influence of ClpC2 on the ClpC1P1P2 protease [1].

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].