bromodomains

NHWD-870 是一种有效且特异性的 BET 家族溴结构域抑制剂，仅与 BRD2、BRD3、BRD4 (IC50 = 2.7 nM) 和 BRDT 结合。 NHWD-870 具有强大的抗肿瘤功效，并通过增加肿瘤细胞凋亡和抑制肿瘤增殖来抑制癌细胞-巨噬细胞相互作用。

ZL0420 是有效且选择性的 BET 溴结构域 4 (BRD4) 抑制剂，对 BRD4 的溴结构域 (BD) 具有纳摩尔结合亲和力。ZL0420 对 BRD4 BD1和 BRD4 BD2 的IC50分别为 27 nM 和 32 nM。

PFI-3是一种选择性，可渗透细胞的SMARCA2 4溴结构域抑制剂，Kd 值为89 nM，可延迟和预防乳腺癌。

FKBP12 PROTAC dTAG-7 (dTAG-7) is a heterobifunctional compound that selectively degrades the BET bromodomain transcriptional co-activator BRD4 by connecting BET bromodomains to the E3 ubiquitin ligase CRBN. Additionally, it serves as a degrader of FKBP12F36V when FKBP12F36V is expressed in-frame with a targeted protein.

NEO2734 (EP31670) 是一种具有口服活性的选择性 p300 CBP 和 BET 溴结构域抑制剂，其 IC50值均小于30 nM，可用于前列腺癌的研究。

RVX-297 是口服具有活性的，对BD2有选择性的BET 高效抑制剂，作用于BRD2(BD2)、BRD3(BD2)、BRD4(BD2) 的IC50分别为 0.08、0.05、0.02 μM。它能够阻碍多种免疫细胞炎症基因的表达，对临床前模型急性炎症及自身免疫均有效。

PF-CBP1 是一种高选择性的 CREB ​​结合蛋白 (CREBBP) 溴结构域抑制剂。它抑制 CREBBP (IC50: 125 nM) 和 p300 溴结构域 (IC50: 363 nM)。

FKBP12 PROTAC dTAG-13是一种PROTAC和选择性降解剂，通过接合FKBP12 F36V和CRBN从而降解 FKBP12 F36V，可用于药物发现过程中的靶标验证。

GNE-987 is a highly active chimeric BET degrader. GNE-987 binds equipotently to the BD1 and BD2 bromodomains of BRD4 with low nanomolar affinities (IC50: 4.7 and 4.4 nM, respectively). GNE-987 exhibits picomolar cell BRD4 degradation activity (DC50: 0.03

(S)-GNE-987 binds to the BRD4 BD1(IC50=4 nM) and BD2 (3.9 nM) bromodomains and can be used to design PROTAC-Antibody Conjugate (PAC).

BAZ2-ICR is an epigenetic chemical probe and it also is a potent, selective, cell active and orally active BAZ2A B bromodomains inhibitor with IC50s of 130 nM and 180 nM, and Kds of 109 nM and 170 nM, respectively. BAZ2-ICR shows 10-15-fold selectivity for binding BAZ2A B over CECR2 and >100-fold selectivity over all other bromodomains.

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).

LP99 是一种表观遗传探针，可破坏 BRD7 和 BRD9 与细胞中染色质的结合。它是一种选择性的 BRD7 和 BRD9 溴结构域抑制剂，对 BRD9 的 Kd 为 99 nM。

MS436 是溴结构域抑制剂，作用于 BRD4 BrD1的Ki 为 30 到 50 nM 之间，比作用于 BrD2 选择性高 10 倍。

GSK 5959 是一种选择性的、细胞渗透性的BRPF1溴端结构域的抑制剂，其IC50值为 80 nM。她对 BRPF1 的选择性是 35 个其他溴结构域的 100 倍以上。

Bromodomain inhibitor-13 （Compound 1）为PFI-3的衍生物，属于含溴结构域蛋白（BCP）抑制剂类。该化合物特别针对SMARCA2、SMARCA4、PB1(5)及PB1的第二个溴结构域（PB1(2)），其KD值分别达37 nM、53 nM、30 nM和190 nM。

DDO-8958 是一种口服活性选择性BET BD1抑制剂，对BRD4 BD1的KD为5.6 nM。除了BRDT BD1之外，DDO-8958对所有BET BD1溴结构域均表现出低纳摩尔级的抑制活性。它还能够抑制肿瘤细胞的增殖和迁移，诱导凋亡 (apoptosis) 和细胞周期阻滞，展现了抗肿瘤活性。

GSK2801 是一种有口服活性的和细胞活性的乙酰赖氨酸竞争性BAZ2A 和BAZ2B 溴结构域选择性抑制剂，Kd 值分别为 136 nM 和 257 nM。

BDOIA383 is a novel inhibitor of CBP/p300 Bromodomains.

CPI098 is a potent and selective inhibitors for the bromodomains of CREBBP EP300. CREBBP EP300 bromodomains play a critical role in regulatory T cell biology. T cell recruitment to tumors is a major mechanism of immune evasion by cancer cells.

CPI571 is a potent and selective inhibitor for the bromodomains of CREBBP EP300.

PF-CBP1 hydrochloride (PF-CBP1 HCl) 是 CREB 结合蛋白溴结构域的一种高选择性抑制剂，抑制 CREBBP 和 EP300溴结构域的 IC50分别为 125 和 363 nM。它降低 LPS 诱导的巨噬细胞中炎症因子的表达，也可下调皮质神经元 RGS4 的表达，可用于癫痫和帕金森病等神经疾病的研究。

High affinity and selective cell-permeable p300/CBP-associated factor (PCAF) inhibitor (Ki = 47 nM). Exhibits no significant activity against a panel of 48 other bromodomains except GCN5 (Kd = 600 nM). Exhibits >4500-fold selectivity for PCAF over BRD4. Also exhibits metabolic stability in mouse and human liver microsomes and no observable cytotoxicity in peripheral blood mononuclear cells (PBMC). Moustakim et al (2017) Discovery of a PCAF bromodomain chemical probe. Angew.Chem.Int.Ed. 56 827 PMID:27966810

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.