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

ABT-263 (Navitoclax) 在一些但不是所有類型的衰老細(xì)胞中具有衰老作用:Navitoclax 降低衰老的人臍靜脈上皮細(xì)胞 (HUVEC)、IMR90 人肺成纖維細(xì)胞和鼠胚胎成纖維細(xì)胞 (MEF) 的活力[2]。 Navitoclax (1μM ; 60 hours)主要通過抑制Bcl-xL[8]加速細(xì)胞凋亡。

ABT-263 (Navitoclax) 在 8 種卵巢癌細(xì)胞系中表現(xiàn)出適度的 (IC50=3-8 μM) 單藥效力。 Navitoclax(0.4μM;30h) 增強(qiáng) Igrov-1 細(xì)胞中卡鉑和/或紫杉醇誘導(dǎo)的半胱天冬酶 3/7 的激活[3]。從 vavP-Bcl-2 轉(zhuǎn)基因小鼠的胸腺或 BM 中分離出的多個淋巴亞群對 ABT-263 (Navitoclax)[4] 明顯更敏感。

ABT-263 (Navitoclax)（100 mg/kg/d；p.o；每日一次，持續(xù) 21 天）處理接種 H345 細(xì)胞的小鼠模型，觀察到顯著的抗腫瘤功效[6] . Navitoclax 聯(lián)合維奈托克和化療對復(fù)發(fā)/難治性急性淋巴細(xì)胞白血病或淋巴細(xì)胞淋巴瘤患者具有良好的耐受性，并具有良好的療效[5]。在代表 9 種不同組織學(xué)的 44 個異種移植模型中，ABT-263 (Navitoclax)（100 mg/kg/d；i.g；21 天）證明了針對 PPTP（兒科臨床前測試程序）實體瘤組的有限單一藥劑體內(nèi)活性，但顯示出顯著的ALL 面板中針對異種移植物的活性[7]。

產(chǎn)品性質(zhì)：

Cas No.:923564-51-6

別名:Navitoclax,ABT-263,ABT263,ABT 263

化學(xué)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

儲存條件:Desiccate at -20°C

注意事項：

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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.