brdt

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.

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.

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.

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.

NHWD-870 is an effective and selective inhibitor of BET family bromodomain only binding to BRD2, BRD3, BRD4 (IC50 = 2.7 nM), and BRDT. NHWD-870 exhibits potent anti-tumor efficacies and suppresses cancer cell-macrophage interaction through the increase of tumor apoptosis and inhibition of tumor proliferation.

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.

CDD-1102 HCl is a novel BRDT-BD4 BRD2-BD1302 selective inhibitor that shows non-hormonal contraceptive potential in ex vivo experiments.

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.

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.

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.

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.

BET bromodomain inhibitor 1 is an orally active, selective inhibitor of bromodomain and extra-terminal (BET) proteins, specifically inhibiting BRD4 with an IC50 of 2.6 nM. It also demonstrates high affinities towards BRD2(2), BRD3(2), BRD4(1), BRD4(2), and BRDT(2) with Kd values of 1.3 nM, 1.0 nM, 3.0 nM, 1.6 nM, and 2.1 nM, respectively. This compound exhibits anti-cancer activity.

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.

FT-1101 is an orally bioavailable, potent and selective BET inhibitor. FT-1101 binds to the acetylated lysine recognition motifs in the bromodomain sites of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histones. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to the inhibition of tumor cell growth. BET proteins, comprised of BRD2, BRD3, BRD4 and BRDT, are transcriptional regulators that play an important role during development and cellular growth.

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.

BD-IN-1, a pan bromodomain (BD) inhibitor, exhibits K_D values of 250 nM for BRD4(1), 420 nM for CBP, 130 nM for BRPF1B, 430 nM for BRD7, 67 nM for BRD9, 240 nM for BRDT(1), and 970 nM for CECR2, respectively. This compound demonstrates antiproliferative activity [1].

NC-III-49-1 is a potent bivalent bromodomain and extraterminal domain (BET) inhibitor with significant affinity for various BRD4 and BRDT isoforms, as demonstrated by its Kd values of 0.095 nM for BRD4-1, 0.32 nM for BRD4-2, 0.29 nM for BRD4-T, 0.089 nM for BRDT-1, 5.5 nM for BRDT-2, and 0.058 nM for BRDT-T. Additionally, NC-III-49-1 exhibits antiproliferative effects and reduces the expression of c-Myc [1].

GXH-II-052 is a potent bivalent inhibitor targeting the bromodomain and extraterminal domain (BET), exhibiting significant binding affinity to various BET proteins, including BRD4-1, BRD4-2, BRD4-T, BRDT-1, BRDT-2, and BRDT-T, with dissociation constants (Kd) of 28, 9.1, 4.8, 0.6, 8.4, and 2.6 nM, respectively. Additionally, GXH-II-052 demonstrates antiproliferative effects and reduces the expression of c-Myc [1].

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].

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].

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.

N1-[5-[[[3-(4-Methoxyphenyl)-1-methyl-1H-indazol-5-yl]carbonyl]amino]-2-methylphenyl]-N4-methyl-1,4-benzenedicarboxamide (ACI) in BD2 DEC-Tec assay with an affinity value of 521 nM.

N-[5-[[[3-(6-Amino-4-methylpyridin-3-yl)-1-methyl-1H-indazol-5-yl]carbonyl]amino]-2-methylphenyl]-N′-methylterephthalamide had an IC50 value of 22 nM in a BD2 DEC-Tec assay.