Home>>Signaling Pathways>> Apoptosis>> Bcl-2 Family>>ABT-263 (Navitoclax)

ABT-263 (Navitoclax) Sale

(Synonyms: Navitoclax,ABT-263,ABT263,ABT 263) 目录号 : GC12405

An inhibitor of Bcl-2 family proteins

ABT-263 (Navitoclax) Chemical Structure

Cas No.:923564-51-6

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥756.00
现货
5mg
¥389.00
现货
10mg
¥525.00
现货
50mg
¥1,512.00
现货
100mg
¥2,457.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

客户使用产品发表文献 2

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Kinase experiment [1]:

Preparation Method

Ki or IC50 values of ABT-263 (Navitoclax) on different subtypes of the Bcl-2 family were determined by competitive fluorescence polarization assay using the following peptide probe pairs or protein pairs :f-bad (1 nM) and Bcl-xL (6 nM), f-Bax (1 nM) and Bcl-2 (10 nM),f-Bax (1 nM) and Bcl-w (40 nM), f-Noxa (2 nM) and Mcl-1 (40 nM),and f-Bax (1 nM) and Bcl-2-A1 (15 nM) were used to determine the binding tightness of ABT-263 and Bcl-xL by time-resolved fluorescence resonance energy transfer method. Bcl-xL with His label was used for 1 nM and 200 nM f-Bak and 1 nMTb-labeled His antibodies were mixed and then treated at room temperature for 30 minutes.

Applications

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ¡ܰ.5 nM, ¡ܱ nM and ¡ܱ nM respectively.

Cell experiment [2]:

Cell lines

HeLa, U2OS, OVCAR-5, and A549 cell

Preparation Method

In four cancer cell lines, nvitokera (ABT-263) was treated with 1 ¦̭ol/L alone or in combination with other agents. Individual cells were monitored by phase-contrast and fluorescence time-lapse microscopy, and time from mitotic entry to morphologic death was measured and plotted as cumulative survival curves.

Reaction Conditions

1μM ;60 hours

Applications

Navitoclax accelerates apoptosis mainly by inhibiting Bcl-xL.

Animal experiment [3]:

Animal models

H345 transplanted tumor model(C.B.-17 scid-bg (scid-bg) or C.B.-17 scid (scid) mice)

Preparation Method

Mice were implanted with H345 cells maintained by in vivo propagation. Noculation volume was 0.2 mL consisting of 50% Matrigel. When tumors reached the appropriate tumor volume, mice were size matched (day 0) into treatment(ABT-263 (Navitoclax)) and control groups.

Dosage form

100 mg/kg/day ABT-263 (Navitoclax);p.o. ;once daily for 21 days

Applications

ABT-263 (Navitoclax) treated a mouse model inoculated with H345 cells, and significant antitumor efficacy was observed.

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].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.

[3]. 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.

产品描述

ABT-263 (Navitoclax) is a inhibitor of Bcl-xL, Bcl-2 and Bcl-w, with Ki ≤0.5 nM, ≤1 nM and ≤1 nM respectively[1].

ABT-263 (Navitoclax) is senolytic in some, but not all types of senescent cells: Navitoclax reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs)[2]. Navitoclax (1μM ; 60 hours) accelerates apoptosis mainly by inhibiting Bcl-xL[8].

ABT-263 (Navitoclax)exhibited modest (IC50=3-8 μM) single agent potency in 8 ovarian cancer cell lines. Navitoclax(0.4μM;30h) enhanced the activation of caspase 3/7 induced by carboplatin and/or paclitaxel in Igrov-1 cells [3]. Multiple lymphoid subpopulations isolated from the thymi or BM of vavP-Bcl-2 transgenic mice were markedly more sensitive to ABT-263 (Navitoclax)[4].

ABT-263 (Navitoclax) (100 mg/kg/d;p.o;once daily for 21 days) treated a mouse model inoculated with H345 cells, and significant antitumor efficacy was observed [6]. Navitoclax with venetoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma[5]. In 44 xenograft models representing 9 different histologies, ABT-263 (Navitoclax) (100 mg/kg/d;i.g; 21 days)demonstrated limited single agent in vivo activity against the PPTP's(pediatric preclinical testing program)solid tumor panels but showed significant activity against xenografts in the ALL panel [7].

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.

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]

Chemical Properties

Cas No. 923564-51-6 SDF
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
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 1.0261 mL 5.1303 mL 10.2605 mL
5 mM 0.2052 mL 1.0261 mL 2.0521 mL
10 mM 0.1026 mL 0.513 mL 1.0261 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置

Research Update

ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor

Overexpression of the prosurvival Bcl-2 family members (Bcl-2, Bcl-xL, and Mcl-1) is commonly associated with tumor maintenance, progression, and chemoresistance. We previously reported the discovery of ABT-737, a potent, small-molecule Bcl-2 family protein inhibitor. A major limitation of ABT-737 is that it is not orally bioavailable, which would limit chronic single agent therapy and flexibility to dose in combination regimens. Here we report the biological properties of ABT-263, a potent, orally bioavailable Bad-like BH3 mimetic (K(i)'s of <1 nmol/L for Bcl-2, Bcl-xL, and Bcl-w). The oral bioavailability of ABT-263 in preclinical animal models is 20% to 50%, depending on formulation. ABT-263 disrupts Bcl-2/Bcl-xL interactions with pro-death proteins (e.g., Bim), leading to the initiation of apoptosis within 2 hours posttreatment. In human tumor cells, ABT-263 induces Bax translocation, cytochrome c release, and subsequent apoptosis. Oral administration of ABT-263 alone induces complete tumor regressions in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia. In xenograft models of aggressive B-cell lymphoma and multiple myeloma where ABT-263 exhibits modest or no single agent activity, it significantly enhances the efficacy of clinically relevant therapeutic regimens. These data provide the rationale for clinical trials evaluating ABT-263 in small-cell lung cancer and B-cell malignancies. The oral efficacy of ABT-263 should provide dosing flexibility to maximize clinical utility both as a single agent and in combination regimens.

The Cancer SENESCopedia: A delineation of cancer cell senescence

Cellular senescence is characterized as a stable proliferation arrest that can be triggered by multiple stresses. Most knowledge about senescent cells is obtained from studies in primary cells. However, senescence features may be different in cancer cells, since the pathways that are involved in senescence induction are often deregulated in cancer. We report here a comprehensive analysis of the transcriptome and senolytic responses in a panel of 13 cancer cell lines rendered senescent by two distinct compounds. We show that in cancer cells, the response to senolytic agents and the composition of the senescence-associated secretory phenotype are more influenced by the cell of origin than by the senescence trigger. Using machine learning, we establish the SENCAN gene expression classifier for the detection of senescence in cancer cell samples. The expression profiles and senescence classifier are available as an interactive online Cancer SENESCopedia.

Next Generation Therapeutics for the Treatment of Myelofibrosis

Myelofibrosis is a myeloproliferative neoplasm characterized by splenomegaly, constitutional symptoms, bone marrow fibrosis, and a propensity towards transformation to acute leukemia. JAK inhibitors are the only approved therapy for myelofibrosis and have been successful in reducing spleen and symptom burden. However, they do not significantly impact disease progression and many patients are ineligible due to coexisting cytopenias. Patients who are refractory to JAK inhibition also have a dismal survival. Therefore, non-JAK inhibitor-based therapies are being explored in pre-clinical and clinical settings. In this review, we discuss novel treatments in development for myelofibrosis with targets outside of the JAK-STAT pathway. We focus on the mechanism, preclinical rationale, and available clinical efficacy and safety information of relevant agents including those that target apoptosis (navitoclax, KRT-232, LCL-161, imetelstat), epigenetic modulation (CPI-0610, bomedemstat), the bone marrow microenvironment (PRM-151, AVID-200, alisertib), signal transduction pathways (parsaclisib), and miscellaneous agents (tagraxofusp. luspatercept). We also provide commentary on the future of therapeutic development in myelofibrosis.

Venetoclax and Navitoclax in Combination with Chemotherapy in Patients with Relapsed or Refractory Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma

Combining venetoclax, a selective BCL2 inhibitor, with low-dose navitoclax, a BCL-XL/BCL2 inhibitor, may allow targeting of both BCL2 and BCL-XL without dose-limiting thrombocytopenia associated with navitoclax monotherapy. The safety and preliminary efficacy of venetoclax with low-dose navitoclax and chemotherapy was assessed in this phase I dose-escalation study (NCT03181126) in pediatric and adult patients with relapsed/refractory (R/R) acute lymphoblastic leukemia or lymphoblastic lymphoma. Forty-seven patients received treatment. A recommended phase II dose of 50 mg navitoclax for adults and 25 mg for patients <45 kg with 400 mg adult-equivalent venetoclax was identified. Delayed hematopoietic recovery was the primary safety finding. The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) proceeded to transplantation or CAR T-cell therapy on study. Venetoclax with navitoclax and chemotherapy was well tolerated and had promising efficacy in this heavily pretreated patient population. SIGNIFICANCE: In this phase I study, venetoclax with low-dose navitoclax and chemotherapy was well tolerated and had promising efficacy in patients with relapsed/refractory acute lymphoblastic leukemia or lymphoblastic lymphoma. Responses were observed in patients across histologic and genomic subtypes and in those who failed available therapies including stem cell transplant.See related commentary by Larkin and Byrd, p. 1324.This article is highlighted in the In This Issue feature, p. 1307.

Bcl-2/Bcl-xL inhibitor ABT-263 overcomes hypoxia-driven radioresistence and improves radiotherapy

Hypoxia, a characteristic of most human solid tumors, is a major obstacle to successful radiotherapy. While moderate acute hypoxia increases cell survival, chronic cycling hypoxia triggers adaptation processes, leading to the clonal selection of hypoxia-tolerant, apoptosis-resistant cancer cells. Our results demonstrate that exposure to acute and adaptation to chronic cycling hypoxia alters the balance of Bcl-2 family proteins in favor of anti-apoptotic family members, thereby elevating the apoptotic threshold and attenuating the success of radiotherapy. Of note, inhibition of Bcl-2 and Bcl-xL by BH3-mimetic ABT-263 enhanced the sensitivity of HCT116 colon cancer and NCI-H460 lung cancer cells to the cytotoxic action of ionizing radiation. Importantly, we observed this effect not only in normoxia, but also in severe hypoxia to a similar or even higher extent. ABT-263 furthermore enhanced the response of xenograft tumors of control and hypoxia-selected NCI-H460 cells to radiotherapy, thereby confirming the beneficial effect of combined treatment in vivo. Targeting the Bcl-2 rheostat with ABT-263, therefore, is a particularly promising approach to overcome radioresistance of cancer cells exposed to acute or chronic hypoxia with intermittent reoxygenation. Moreover, we found intrinsic as well as ABT-263- and irradiation-induced regulation of Bcl-2 family members to determine therapy sensitivity. In this context, we identified Mcl-1 as a resistance factor that interfered with apoptosis induction by ABT-263, ionizing radiation, and combinatorial treatment. Collectively, our findings provide novel insights into the molecular determinants of hypoxia-mediated resistance to apoptosis and radiotherapy and a rationale for future therapies of hypoxic and hypoxia-selected tumor cell fractions.