ABT-263 (Navitoclax) 是 Bcl-xL、Bcl-2 和 Bcl-w 的抑制剂，Ki 分别≤0.5 nM、≤1 nM 和≤1 nM[1]。

ABT-263 (Navitoclax) 在一些但不是所有类型的衰老细胞中具有衰老作用:Navitoclax 降低衰老的人脐静脉上皮细胞 (HUVEC)、IMR90 人肺成纤维细胞和鼠胚胎成纤维细胞 (MEF) 的活力[2]。 Navitoclax (1μM ; 60 hours)主要通过抑制Bcl-xL[8]加速细胞凋亡。

ABT-263 (Navitoclax) 在 8 种卵巢癌细胞系中表现出适度的 (IC50=3-8 μM) 单药效力。 Navitoclax(0.4μM;30h) 增强 Igrov-1 细胞中卡铂和/或紫杉醇诱导的半胱天冬酶 3/7 的激活[3]。从 vavP-Bcl-2 转基因小鼠的胸腺或 BM 中分离出的多个淋巴亚群对 ABT-263 (Navitoclax)[4] 明显更敏感。

ABT-263 (Navitoclax)（100 mg/kg/d；p.o；每日一次，持续 21 天）处理接种 H345 细胞的小鼠模型，观察到显着的抗肿瘤功效[6] . Navitoclax 联合维奈托克和化疗对复发/难治性急性淋巴细胞白血病或淋巴细胞淋巴瘤患者具有良好的耐受性，并具有良好的疗效[5]。在代表 9 种不同组织学的 44 个异种移植模型中，ABT-263 (Navitoclax)（100 mg/kg/d；i.g；21 天）证明了针对 PPTP（儿科临床前测试程序）实体瘤组的有限单一药剂体内活性，但显示出显着的ALL 面板中针对异种移植物的活性[7]。

产品性质：

Cas No.:923564-51-6

别名:Navitoclax,ABT-263,ABT263,ABT 263

化学名: (R)-4-(4-((4'-chloro-4,4-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((4-morpholino-1-(phenylthio)butan-2-yl)amino)-3-((trifluoromethyl)sulfonyl)phenyl)sulfonyl)benzamide

Canonical SMILES: CC(CC1)(C)CC(CN2CCN(C3=CC=C(C(NS(C4=CC=C(N[C@@H](CSC5=CC=CC=C5)CCN6CCOCC6)C(S(C(F)(F)F)(=O)=O)=C4)(=O)=O)=O)C=C3)CC2)=C1C7=CC=C(Cl)C=C7

分子式:C47H55ClF3N5O6S3

分子量:974.61

溶解度:≥ 48.7305mg/mL in DMSO

储存条件:Desiccate at -20°C

注意事项：

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References:

[1]. Tse C, Shoemaker AR, et,al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 2008 May 1;68(9):3421-8. doi: 10.1158/0008-5472.CAN-07-5836. PMID: 18451170.

[2]. Zhu Y, Tchkonia T, et,al.Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016 Jun;15(3):428-35. doi: 10.1111/acel.12445. Epub 2016 Mar 18. PMID: 26711051; PMCID: PMC4854923.

[3]. Stamelos VA, Robinson E, et,al. Navitoclax augments the activity of carboplatin and paclitaxel combinations in ovarian cancer cells. Gynecol Oncol. 2013 Feb;128(2):377-82. doi: 10.1016/j.ygyno.2012.11.019. Epub 2012 Nov 17. PMID: 23168176.

[4]. Mérino D, Khaw SL, et,al. Bcl-2, Bcl-x(L), and Bcl-w are not equivalent targets of ABT-737 and navitoclax (ABT-263) in lymphoid and leukemic cells. Blood. 2012 Jun 14;119(24):5807-16. doi: 10.1182/blood-2011-12-400929. Epub 2012 Apr 26. PMID: 22538851; PMCID: PMC3382939.

[5]. Pullarkat VA, Lacayo NJ, et,al.Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. Cancer Discov. 2021 Jun;11(6):1440-1453. doi: 10.1158/2159-8290.CD-20-1465. Epub 2021 Feb 16. PMID: 33593877; PMCID: PMC9533326.

[6]. Shoemaker AR, Mitten MJ, et,al. Activity of the Bcl-2 family inhibitor ABT-263 in a panel of small cell lung cancer xenograft models. Clin Cancer Res. 2008 Jun 1;14(11):3268-77. doi: 10.1158/1078-0432.CCR-07-4622. PMID: 18519752.

[7]. Lock R, Carol H, et,al. Initial testing (stage 1) of the BH3 mimetic ABT-263 by the pediatric preclinical testing program. Pediatr Blood Cancer. 2008 Jun;50(6):1181-9. doi: 10.1002/pbc.21433. PMID: 18085673.

[8].Shi J, Zhou Y, Huang HC, Mitchison TJ. Navitoclax (ABT-263) accelerates apoptosis during drug-induced mitotic arrest by antagonizing Bcl-xL. Cancer Res. 2011 Jul 1;71(13):4518-26. doi: 10.1158/0008-5472.CAN-10-4336. Epub 2011 May 5. PMID: 21546570; PMCID: PMC3129452.