128517-07-7

• 常用中文名：罗米地辛
• 常用英文名：Romidepsin (FK228, Depsipeptide)
• CAS号：128517-07-7
• 分子式：C₂₄H₃₆N₄O₆S₂
• 分子量：540.696
• 相关类别： 生物化工 抑制剂 表观遗传学(Epigenetics) HDAC 抑制剂
• 发布时间：2018-09-14 13:19:01
• 更新时间：2026-07-01 20:34:01
• Romidepsin 是一种有效的 HDAC1 和 HDAC2 抑制剂,IC50 值分别为 36 nM 和 47 nM。

名称

• 中文名: 罗米地辛
• 英文名: romidepsin
• 中文别名: (1S,4S,7Z,10S,16E,21R)-7-亚乙基-4,21-二异丙基-2-氧杂-12,13-二硫杂-5,8,20,23-四氮杂双环[8.7.6]二十三烷-16-烯-3,6,9,19,22-五酮; 抗生素 FR901228; FK228 罗米地辛; 抑制剂Romidsin; 罗米地辛抑制剂; 罗米地辛, 一种有效的HDAC1和HDAC2抑制剂; 罗米地辛 (FK228, DSIPTIDE); 化合物:Romidsin (FK228, dsiptide); 化合物：Romidsin (FK228, dsiptide); ROMIDSIN,HDAC1和HDAC2抑制剂; 2-氧杂-12,13-二硫杂-5,8,20,23-四氮杂双环[8.7.6]三十烷,环肽衍生物; HDAC1和HDAC2抑制剂(ROMIDSIN)
• 英文别名: FK 228; FR 901228; NSC 630176; DSIPTIDE;FK228; Romidsin D7Q: What is Romidsin D7 Q: What is the CAS Number of Romidsin D7 Q: What is the storage condition of Romidsin D7 Q: What e the applications of Romidsin D7; dsiptide; Romidsin a potent HDAC1 and HDAC2 inhibitor; (1S,4S,7Z,10S,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone; (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18,21-tetrazabicyclo[8.7.6]tricos-11-ene-2,5,8,19,22-pentone; Romidsin Antibiotic FR; Chromadax; Romidsin; Antibiotic FR; Cyclo[(2Z)-2-amino-2-butenoyl-L-valyl-(3S,4E)-3-hydroxy-7-Mercapto-4-htenoyl-D-valyl-D-cysteinyl],cyclic (3®; Romidepsin; Istodax; FK228, Dsiptide; (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18,21-tetrazabicyclo[8.7.6]tricos-11-ene-2,5,8,19,22-pentone //BP; istodax; (1S,4S,7Z,10S,16E,21R)-7-ethylidene-4,21-di(propan-2-yl)-2-oxa-12,13-dithia-5,8,20,23-tetrazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone; GSI-001; FK-228; Romidsin (FK228, FR901228, Dsiptide, NSC630176); GS-003; (1S,4S,7Z,10S,21R)-7-Ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone; Romidsin - Bio-X; GS-002; (1S,4S,7Z,10S,16E,21R)-7-Ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentaone; FK228 Romidsin FK-228; [S-(E)]-N-(3-Hydroxy-7-Mercapto-1-oxo-4- htenyl)-D-valyl-D-cysteinyl-(Z)-2,3-didehydro-2-aMinobutanoyl; Romidsin (FK228, Dsiptide, FR1228); RoMidsin-d8; (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7; (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18,21-tetrazabicyclo[; Cyclo[(2Z)-2-amino-2-butenoyl-L-valyl-(3S,4E)-3-hydroxy-7-Mercapto-4-htenoyl-D-valyl-D-cysteinyl]-d8 Cyclic (35)-Disulfide; FK228 RoMidsin; Cyclo[(2Z)-2-amino-2-butenoyl-L-valyl-(3S,4E)-3-hydroxy-7-Mercapto-4-htenoyl-D-valyl-D-cysteinyl] Cyclic (35)-Disulfide; (1S,4S,7Z,10S,16Z,21R)-7-Ethylidene-4,21-diisopropyl-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone; Romidixin; 5)-disulfide; Romidisin; FK228; (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18,21-tetrazabicyclo[8.7.6]tricos-11-ene-2,5,8,19,22-pentone RoMidsin (FK228, Dsiptide); RoMidsin/Dsiptide(FK-228, NSC-63017); RoMidsin(FK228); (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18; Depsipeptide; Romidepsin (FK228,depsipeptide); Romidsin, >=; RoMidsin (FK228 ,Dsiptide); (1S,4Z,7S,10S,11E,20R)-4-ethylidene-7,20-dipropan-2-yl-9-oxa-15,16-dit hia-3,6,18,21-tetrazabicyclo[8.7.6]tricos-11-ene-2,5,8,19,23-pentone

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 942.8±65.0 °C at 760 mmHg
• 熔点: 219-224°C
• 分子式: C₂₄H₃₆N₄O₆S₂
• 分子量: 540.696
• 闪点: 524.0±34.3 °C
• 精确质量: 540.207642
• PSA: 193.30000
• LogP: 0.95
• 蒸汽压: 0.0±0.3 mmHg at 25°C
• 折射率: 1.529
• 储存条件: Amber Vial, -20°C Freezer, Under Inert Atmosphere

生物活性

• 描述: Romidepsin 是一种有效的 HDAC1 和 HDAC2 抑制剂,IC50 值分别为 36 nM 和 47 nM。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> HDAC
  信号通路 >> 表观遗传学 >> HDAC
  研究领域 >> 癌症
• 靶点:

  HDAC1:36 nM (IC50)

  HDAC2:47 nM (IC50)

  HDAC4:510 nM (IC50)

  HDAC6:14000 nM (IC50)

• 体外研究: 罗米地辛有效抑制HDAC1和HDAC2(IC50 = 36,47 nM,分别)。罗米地辛对HDAC4和HDAC6具有轻微抑制作用(IC50 = 510,14000nM)。罗米地辛诱导组蛋白乙酰化和p21表达,EC50为3.0 nM。由于redFK在HeLa细胞中的不稳定性,Romidepsin比redFK更强,EC50为11 nM [1]。 Romidepsin的效力是TSA的100倍,在抑制A549细胞增殖方面比丁酸盐强1,000,000倍。 Romidepsin导致有丝分裂停滞,HDIs治疗导致有丝分裂染色体分离缺陷[2]。罗米地辛抑制U-937,K562和CCRF-CEM细胞的生长,IC50值分别为5.92 nM,8.36 nM和6.95 nM [3]。
• 体内研究: 在scid小鼠淋巴瘤模型中,罗米地辛治疗小鼠每周一次或两次比对照小鼠存活时间更长,中位生存时间分别为30.5(0.56 mg/kg)和33天(0.32 mg/kg)(相对于20天)控制小鼠)。值得注意的是,用罗米地辛治疗的12只小鼠中有2只(0.56mg/kg,每周一次或两次)在60天的观察期后存活。在用罗米地辛处理48小时后,U-937细胞的凋亡群体以时间依赖性方式增加至37.7％。此外,罗米地辛诱导G1和G2/M阻滞以及U-937细胞分化为CD11b(+)/ CD14(+)表型。在用罗米地辛处理24小时后,p21(WAF1/Cip1)和凝溶胶蛋白mRNA的表达分别增加至654倍和152倍。 Romidepsin在p21(WAF1/Cip1)启动子区域引起组蛋白乙酰化,包括Sp1结合位点[3]。
• 激酶实验: 对于酶测定，将10μL[3H]乙酰基标记的组蛋白（25,000cpm /10μg）加入到90μL从过量表达HDAC1或HDAC2的293T细胞中提取的HDAC酶级分中，在增加浓度的罗米地辛存在下，和将混合物在37℃下温育15分钟。酶反应是线性的至少1小时。加入10μL浓HCl终止反应。用1mL乙酸乙酯萃取释放的[3H]乙酸，并将0.9mL溶剂层加入5mL含水计数闪烁液II水溶液中以测定放射性。 IC50值由至少三个独立的剂量 - 反应曲线确定。
• 细胞实验: 将细胞在96孔板中暴露于各种浓度的罗米地辛72小时。向每个孔中加入20μL5mg/ mL MTT的PBS溶液4小时。除去培养基后，向各孔中加入170μLDMSO以溶解甲crystals晶体。测定540nm处的吸光度。另外，将细胞与台盼蓝一起孵育，并在血细胞计数器中计数蓝色（死亡）细胞和透明（活）细胞的数量。对于细胞周期分析，将细胞在含有0.05mg / mL碘化丙啶，1mM EDTA，0.1％Triton X-100和PBS中1mg / mL RNase A的碘化丙锭染色溶液中孵育30分钟。然后使悬浮液通过尼龙筛网过滤器并在Becton Dickinson FACScan上分析。
• 动物实验: 简而言之，腹膜内注射150mg / kg环磷酰胺的雄性scidmice。所有注射环磷酰胺的小鼠仅在观察期内存活。环磷酰胺注射后24小时，用500μLPBS中的1×107U-937细胞腹膜内接种小鼠。在肿瘤细胞接种后24小时，用或不用FK228腹膜内处理小鼠，剂量范围为0.1至1mg / kg，每周一次或两次。对照小鼠每周两次用10％HCO60盐水处理。 6只和12只小鼠分别用于FK228处理组和对照组。观察期为细胞接种后60天，通过存活时间评估抗肿瘤效果，通过Peto检验分析其统计学显着性。
• 参考文献:

  [1]. Furumai R, et al. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res. 2002 Sep 1;62(17):4916-21.

  [2]. Blagosklonny MV, et al. Histone deacetylase inhibitors all induce p21 but differentially cause tubulin acetylation, mitotic arrest, and cytotoxicity. Mol Cancer Ther. 2002 Sep;1(11):937-41.

  [3]. Sasakawa Y, et al. Effects of FK228, a novel histone deacetylase inhibitor, on human lymphoma U-937 cells in vitro and in vivo. Biochem Pharmacol. 2002 Oct 1;64(7):1079-90.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : YV9399000 CHEMICAL NAME : L-Valine, N-(3-hydroxy-7-mercapto-1-oxo-4-heptenyl)-D-valyl-D-c ysteinyl-(Z)-2,3-dide hydro-2- aminobutanoyl-, ti-lactone, cyclic (1-2)-disulfide, (S-(E))- CAS REGISTRY NUMBER : 128517-07-7 LAST UPDATED : 199610 DATA ITEMS CITED : 2 MOLECULAR FORMULA : C24-H36-N4-O6-S2 MOLECULAR WEIGHT : 540.76 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 6400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 47,301,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 10 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : JANTAJ Journal of Antibiotics. (Japan Antibiotics Research Assoc., 2-20-8 Kamiosaki, Shinagawa-ku, Tokyo, 141, Japan) V.2-5, 1948-52; V.21- 1968- Volume(issue)/page/year: 47,301,1994

安全

• 危险品运输编码: NONH for all modes of transport
• RTECS号: YV9399000
• 海关编码: 29349990

合成路线