1231930-82-7

• 常用中文名：N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-异丙基-1H-苯并咪唑-6-基]-2-嘧啶胺甲烷磺酸盐
• 常用英文名：Abemaciclib(LY2835219)
• CAS号：1231930-82-7
• 分子式：C₂₈H₃₆F₂N₈O₃S
• 分子量：602.699
• 相关类别： 生物化工 抑制剂 细胞周期(Cell Cycle) CDK 抑制剂
• 发布时间：2016-05-26 06:48:49
• 更新时间：2026-07-16 12:38:13
• Abemaciclib (LY2835219) (methanesulfonate) 是选择性的 CDK4/6 抑制剂,抑制 CDK4/CDK6 的 IC50 分别为 2 nM 和 10 nM。

名称

• 中文名: N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-异丙基-1H-苯并咪唑-6-基]-2-嘧啶胺甲烷磺酸盐
• 英文名: N-[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]-5-fluoro-4-(7-fluoro-2-methyl-3-propan-2-ylbenzimidazol-5-yl)pyrimidin-2-amine,methanesulfonic acid
• 中文别名: 阿贝昔利布甲磺酸盐; Abemaciclib mesylate (LY2835219) 甲磺酸阿贝西尼,S7158; CDK4/6抑制剂(LY2835219); abemaciclib 甲磺酸盐; N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-(1-甲基乙基)-1H-苯并咪; 阿贝西利甲磺酸盐; N-(5-((4-甲基哌嗪-1-基甲基)吡啶-2-基)-5氟-4-(4-氟-1-异丙基-2-甲基-1H-苯并[D]咪唑-6-基)嘧啶-2-胺甲磺酸盐; LY2835219盐; N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-(1-甲基乙基)-1H-苯并咪唑-6-基]-2-嘧啶胺甲烷磺酸酯; 甲磺酸阿贝西利; 阿贝西利甲磺酸; N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-(1-甲基乙基)-1H-苯并咪唑- 6-基]-2-嘧啶胺甲磺酸盐; 玻马西林甲磺酸盐; 甲磺酸LY2835219; LY 2835219N-[5-[(4-乙基-1-哌嗪基)甲基]-2-吡啶基]-5-氟-4-[4-氟-2-甲基-1-异丙基-1H-苯并咪唑-6-基]-2-嘧啶胺甲烷磺酸盐; LY2835219甲磺酸盐; ABEMACICLIB METHANESULFONATE(阿贝西利); Abemaciclib mesylate (LY2835219) 甲磺酸阿贝西尼，S7158
• 英文别名: N-{5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl}-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzimidazol-6-yl)-2-pyrimidinamine methanesulfonate (1:1); Bemaciclib(salt); LY2835219; LY-2835219; LY; QCR-274; LY2835219 mesylate; N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine methanesulfonate (1:1); Abemaciclib mesylate(LY2835219 mesylate); 2-Pyrimidinamine, N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-, methanesulfonate (1:1); LY2835219/LY-2835219; N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine methanesulfonate (1:1) LY2835219; LY2835219; N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine methanesulfonate; CS-1229; 2-Pyrimidinamine, N-[5-[(4-ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimida; N-(5-((4-ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-amine methanesulfonate; N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methylethyl)-1H-benzimidazol-6-yl]-2-pyrimidinamine Methanesulfonate; Abemaciclib (methanesulfonate); ABEMACICLIB LY2835219; Abemaciclib (LY2835219) mesylate; LY2835219 Ms salt, Abemaciclib Ms salt; Abemaciclib mesylate; LY2835219 (methanesulfonate); Abemaciclib Mesylate; Bemaciclib; LY2835219 (Abemaciclib) mesylate; ABEMACICLIB METHANESULFONATE (LY2835219 METHANESULFONATE); Abemaciclib methanesulfonate, 10 mM in DMSO; Bamaciclib Mesylate; UNII-KKT462Q807; N-[5-[(4-Ethyl-1-piperazinyl)methyl]-2-pyridinyl]-5-fluoro-4-[4-fluoro-2-methyl-1-(1-methyle; ABEMACICLIB (LY2835219);LY2835219;LY 2835219;LY-2835219; N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzodimidazol-6-yl)pyrimidin-2-amine mesylate; Abemaciclib mesylate(LY2835219); LY2835219methanesulfonic acid; LY2835219 //BP; N-(5-((4-Ethylpiperazin-1-yl)methyl)pyridin-2-yl)-5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H

物化性质

• 分子式: C₂₈H₃₆F₂N₈O₃S
• 分子量: 602.699
• 精确质量: 602.259888
• PSA: 137.75000
• LogP: 5.47050
• 外观性状: 白色 粉末
• 储存条件: 室温，干燥，密封

生物活性

• 描述: Abemaciclib (LY2835219) (methanesulfonate) 是选择性的 CDK4/6 抑制剂,抑制 CDK4/CDK6 的 IC50 分别为 2 nM 和 10 nM。
• 相关类别:
  信号通路 >> 细胞周期/DNA损伤 >> CDK
  研究领域 >> 癌症
• 靶点:

  Cdk4/cyclin D1:2 nM (IC50)

  CDK6/cyclinD1:10 nM (IC50)

  CDK2/cyclinE:504 nM (IC50)

  CDK9/cyclinT1:57 nM (IC50)

  CDK1/cyclinB1:1627 nM (IC50)

  CDK7/Mat1/cyclinH1:3910 nM (IC50)

  Cdk5/p25:355 nM (IC50)

  CDK5/p35:287 nM (IC50)

  PIM1:50 nM (IC50)

  PIM2:3400 nM (IC50)

  HIPK2:31 nM (IC50)

  DYRK2:61 nM (IC50)

  CK2:117 nM (IC50)

  GSK3b:192 nM (IC50)

  JNK3:389 nM (IC50)

  FLT3 (D835Y):403 nM (IC50)

  FLT3:3960 nM (IC50)

  DRAK1:659 nM (IC50)

• 体外研究: Abemaciclib(LY2835219)降低细胞活力,IC50值范围为0.5μM至0.7μM,抑制Akt和ERK信号,但不抑制头颈部鳞状细胞癌(HNSCC)细胞的mTOR活化[1]。 Abemaciclib(LY2835219)显示对A375R1-4,M14R和SH4R的抑制,EC50值范围为0.3至0.6μM; Abemaciclib抑制亲本A375和抗性A375RV1和A375RV2细胞的增殖,具有相似的效力,IC50值分别为395,260和463 nM [2]。 Abemaciclib(LY2835219)以低纳摩尔效力抑制CDK4和CDK6,抑制Rb磷酸化,导致G1停滞和抑制增殖,其活性对Rb-熟练细胞具有特异性[3]。
• 体内研究: Abemaciclib(LY2835219)(45 mg/kg,口服)与依维莫司联合在HNSCC异种移植肿瘤中引起协同抗肿瘤作用[1]。 Abemaciclib(LY2835219)(45或90mg/kg,po)在A375异种移植模型中显示出显着的肿瘤生长抑制[2]。
• 细胞实验: 将细胞接种在96孔板中，使其粘附过夜，并用DMSO对照（0.1％v / v）或所示化合物处理72小时。使用细胞计数试剂盒根据制造商的说明书测定细胞活力和增殖。使用CompuSyn测定Abemaciclib（LY2835219）和mTOR抑制剂之间的相互作用。组合指数（CI）值1表示添加剂药物相互作用，而CI <1是协同的，CI> 1是拮抗性的。
• 动物实验: 给6周龄BALB / c雌性裸鼠皮下注射OSC-19（1×106）细胞。当肿瘤大小达到约100mm 3时，通过肿瘤大小随机化小鼠并进行每次治疗。每个治疗组包括至少5只小鼠。每组小鼠通过每日口服管饲给予载体，Abemaciclib（LY2835219）（45mg / kg / d或90mg / kg / d），依维莫司（5mg / kg / d）或两者的组合。将Abemaciclib（LY2835219）溶于1％HEC的20mM磷酸盐缓冲液（pH2.0）中。每周两次测量肿瘤大小和体重。使用以下公式计算肿瘤体积：V =（L×W2）/ 2（L，长度; W，宽度）。在第14天对小鼠进行最后一次强饲，并在第二天处死。取出肿瘤进行Western印迹和免疫组织化学。
• 参考文献:

  [1]. Ku BM, et al. The CDK4/6 inhibitor LY2835219 has potent activity in combination with mTOR inhibitor in head and neck squamous cell carcinoma. Oncotarget. 2016 Mar 22;7(12):14803-13.

  [2]. Yadav V, et al. The CDK4/6 inhibitor LY2835219 overcomes vemurafenib resistance resulting from MAPK reactivation and cyclin D1 upregulation. Mol Cancer Ther. 2014 Oct;13(10):2253-63.

  [3]. Gelbert LM, et al. Preclinical characterization of the CDK4/6 inhibitor LY2835219: in-vivo cell cycle-dependent/independent anti-tumor activities alone/in combination with gemcitabine. Invest New Drugs. 2014 Oct;32(5):825-37.

  [4]. Wu T, et al. Effect of abemaciclib (LY2835219) on enhancement of chemotherapeutic agents in ABCB1 and ABCG2 overexpressing cells in vitro and in vivo. Biochem Pharmacol. 2017 Jan 15;124:29-42.