CS-2252
中文名称 | CS-2252 |
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中文同义词 | BRD4抑制剂(ARV-825);(6S)-4-(4-氯苯基)-N-[4-[2-[2-[2-[2-[2-[2-[2-(2,6-二氧代-3-哌啶基)-2,3-二氢-1,3-二氧代-1H-异吲哚-4-基]氨基]乙氧基]乙氧基]乙氧基]乙氧基]苯基]-2,3,9-三甲基-6H-噻吩并[3,2-f][1,2,4]三唑并[4,3-a][1,4]二氮杂6-乙酰胺;化合物ARV-825;(6S)-4-(4-氯苯基)-N-[4-[2-[2-[2-[2-[2-[2-[2-(2,6-二氧代-3-哌啶基)-2,3-二氢-1,3-二氧代-1H-异吲哚-4-基]氨基]乙氧基]乙氧基]乙氧基]乙氧基]苯基]-2,3,9-三甲基-6H-噻吩并[3,2-F][1,2,4]三唑并[4,3-A][1,4]二氮杂6-乙酰胺;2-((S)-4-(4-氯苯基)-2,3,9-三甲基-6H-噻吩并[3,2-F][1,2,4]三唑并[4,3-A][1,4]二氮杂卓-6-基)-N-(4-(2-(2-(2-(2-((2-(2,6-二氧代哌啶-3-基)-1,3-二氧代异吲哚啉-4-基)氨基)乙氧基)乙氧基)乙氧基)乙氧基)苯基)乙酰胺 |
英文名称 | ARV-825 |
英文同义词 | ARV-825;CS-2252;ARV-825;ARV 825;ARV825;AVR-825;6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-N-[4-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]phenyl]-2,3,9-trimethyl-, (6S)-;Epigenetic Reader Domain,inhibit,PROTACs,ARV 825,Inhibitor,ARV825,ARV-825;2-((S)-4-(4-Chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)-N-(4-(2-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethoxy)ethoxy)phenyl)acetamide |
CAS号 | 1818885-28-7 |
分子式 | C46H47ClN8O9S |
分子量 | 923.43 |
EINECS号 | |
相关类别 | 细胞生物学试剂 |
Mol文件 | 1818885-28-7.mol |
结构式 |
CS-2252 性质
密度 | 1.47±0.1 g/cm3(Predicted) |
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储存条件 | 2-8°C(protect from light) |
溶解度 | DMSO:5.0(最大浓度 mg/mL);5.41(最大浓度 mM) DMF:5.0(最大浓度 mg/mL);5.41(最大浓度 mM) 水:0.0(最大浓度 mg/mL);0.0(最大浓度 mM) |
形态 | 结晶固体 |
酸度系数(pKa) | 10.74±0.40(Predicted) |
ARV-825是一种BRD4抑制剂,可招募BRD4到E3泛素连接酶cereblon上,引起BRD4蛋白快速、有效和持续的降解,持续性下调MYC水平。
ARV-825 is a PROTAC (proteolysis-targeting chimera). ARV-825 exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.
Target | Value |
BRD4 BD2
(Cell-free assay) | 28 nM(Kd) |
BRD4 BD1
(Cell-free assay) | 90 nM(Kd) |
与其他BRD4抑制剂比较,在伯基特氏淋巴瘤细胞中,ARV-825的处理可引起c-MYC水平和下游细胞增殖和凋亡诱导发生更为显著的变化。与ARV-825共孵育72小时,ARV-825对所检测细胞系和原代AML细胞的IC50值在2-50 nM范围内。在AML细胞中,ARV-825可降低PIM1水平和CXCR4的磷酸化水平,而PIM1或CXCR4的过表达可逆转该效应。
在移植有人源白血病细胞的小鼠模型中,ARV-825实验组的小鼠的白血病负荷显著低于对照组,其生存时间也较对照组长。
用途
一种BRD4抑制剂,对BRD4的BD1和BD2结构域具有高亲和力,Kd值分别为90和28nM。ARV-825 is a PROTAC (proteolysis-targeting chimera). ARV-825 exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.
安全信息
海关编码 | 2933998090 |
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更新日期 | 产品编号 | 产品名称 | CAS号 | 包装 | 价格 |
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2024/01/25 | HY-16954 | ARV-825 | 1 mg | 590元 | |
2024/01/25 | HY-16954 | CS-2252 ARV-825 | 1818885-28-7 | 5mg | 1300元 |