GlpBio

AMG-176

目录号: GC19452纯度: >99.00%同义词: AMG-176
AMG-176 (Tapotoclax) 是一种有效的、选择性的、具有口服活性的 MCL-1 抑制剂，Ki 为 0.13 nM。
AMG-176
Cas No.: 1883727-34-1
规格价格库存数量操作
1mg¥6,120.00现货
1
5mg¥17,550.00现货
1
电话: 400-920-5774Email: sales@glpbio.cn

文献被引

本产品暂无引用记录;以下为 GlpBio 产品在 Nature / Cell / Science 等顶刊的客户引用样例
  • Nature cover
    Nature
    641, 529–536 (2025)
  • Nature cover
    Nature
    628, 630–638 (2024)
  • Nature cover
    Nature
    632, 686–694 (2024)
  • Nature cover
    Nature
    618, 1017–1023 (2023)
  • Nature cover
    Nature
    610, 366–372 (2022)
  • Cell cover
    Cell
    187(9):2288-2304 (2024)
  • Cell cover
    Cell
    183(7):1867-1883 (2020)
  • Science cover
    Science
    388(6745) (2025)
  • Science cover
    Science
    387(6739) (2025)
  • Science cover
    Science
    387(6734) (2025)
  • Cell Research cover
    Cell Research
    35, 97–116 (2025)
  • Cell Research cover
    Cell Research
    34, 683–706 (2024)
  • Cell Research cover
    Cell Research
    33, 273–287 (2023)
  • Cell Research cover
    Cell Research
    33, 546–561 (2023)
  • Cell Research cover
    Cell Research
    33, 904–922 (2023)
  • Cell Research cover
    Cell Research
    31, 1291–1307 (2021)

产品描述 Description

AMG-176 (Tapotoclax) is a potent, selective and orally active MCL-1 inhibitor, with a Ki of 0.13 nM.?AMG-176 is a potent antagonist of Mcl-1; in cell free system the Ki value is <1 nM. In whole cells, the drug was tested in different leukemias, lymphoma, and multiple myeloma cell lines[1]. AMG-176 incubations resulted in time- and dose-dependent CLL cell death. At 100 and 300 nmol/L, there was 30% and 45% cell death at 24 hours. These concentrations did not result in significant cell death in normal hematopoietic cells. Presence of stroma did not affect AMG-176-induced CLL cell death[4].AMG-176 induced cell death was inversely correlated with endogenous McL-1 levels[5].

AMG-176 has a weak ability to induce apoptosis in C002M melanoma cell line, but a strong ability to induce apoptosis in C057M melanoma cell line. AMG-176 has a synergistic effect with I-BET151 in these two melanoma cell lines[2]. AMG-176 completely neutralized the survival effect of the IDO1/Kyn/AHR pathway in CLL cells[6].

AMG-176 Is Efficacious in Multiple Myeloma. In vivo, Dose-dependent activation of the intrinsic apoptosis pathway in OPM-2 xenografts, as measured by activated BAK, cleaved caspase-3, and cleaved PARP, was detected as early as 2 hours after oral administration of AMG 176, with sustained cleaved PARP and activated BAK detectable through 12 hours and cleaved caspase-3 through 24 hours. Immunohistochemistry analysis revealed a similar dose-dependent increase in cleaved caspase-3[3].

References:
[1]:Garner TP, Lopez A, et,al. Progress in targeting the BCL-2 family of proteins. Curr Opin Chem Biol. 2017 Aug;39:133-142. doi: 10.1016/j.cbpa.2017.06.014. Epub 2017 Aug 17. PMID: 28735187; PMCID: PMC5667545.
[2]: Tseng HY, Dreyer J, et,al.Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma. Int J Cancer. 2020 Oct 15;147(8):2176-2189. doi: 10.1002/ijc.33000. Epub 2020 Apr 24. PMID: 32249419.
[3]: Caenepeel S, Brown SP,et,al. AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. Cancer Discov. 2018 Dec;8(12):1582-1597. doi: 10.1158/2159-8290.CD-18-0387. Epub 2018 Sep 25. Erratum in: Cancer Discov. 2019 Jul;9(7):980. PMID: 30254093.
[4]:Yi X, Sarkar A, et,al. AMG-176, an Mcl-1 Antagonist, Shows Preclinical Efficacy in Chronic Lymphocytic Leukemia. Clin Cancer Res. 2020 Jul 15;26(14):3856-3867. doi: 10.1158/1078-0432.CCR-19-1397. Epub 2020 Jan 14. PMID: 31937611; PMCID: PMC7358119.
[5]: Yi X, Jain N, et,al. Targeting Mcl-1 by AMG-176 During Ibrutinib and Venetoclax Therapy in Chronic Lymphocytic Leukemia. Front Oncol. 2022 Feb 22;12:833714. doi: 10.3389/fonc.2022.833714. PMID: 35273915; PMCID: PMC8901605.
[6]: Atene CG, Fiorcari S, et,al. Indoleamine 2, 3-Dioxygenase 1 Mediates Survival Signals in Chronic Lymphocytic Leukemia via Kynurenine/Aryl Hydrocarbon Receptor-Mediated MCL1 Modulation. Front Immunol. 2022 Mar 18;13:832263. doi: 10.3389/fimmu.2022.832263. PMID: 35371054; PMCID: PMC8971515.

AMG-176 (Tapotoclax) 是一种有效的、选择性的、具有口服活性的 MCL-1 抑制剂，Ki 为 0.13 nM。 AMG-176 是一种有效的 Mcl-1 拮抗剂；在无细胞系统中，Ki 值为 &<1 nM。在全细胞中，该药物在不同的白血病、淋巴瘤和多发性骨髓瘤细胞系中进行了测试[1]。 AMG-176 孵育导致时间和剂量依赖性 CLL 细胞死亡。在 100 和 300 nmol/L 时，24 小时时有 30% 和 45% 的细胞死亡。这些浓度不会导致正常造血细胞显着死亡。基质的存在不影响 AMG-176 诱导的 CLL 细胞死亡[4]。AMG-176 诱导的细胞死亡与内源性 McL-1 水平呈负相关[5] .

AMG-176对C002M黑色素瘤细胞系的凋亡诱导能力较弱，但对C057M黑色素瘤细胞系的凋亡诱导能力较强。 AMG-176 与 I-BET151 在这两种黑色素瘤细胞系中具有协同作用[2]。 AMG-176完全中和IDO1/Kyn/AHR通路对CLL细胞的存活效应[6]。

AMG-176 对多发性骨髓瘤有效。在体内，早在口服 AMG 176 后 2 小时就检测到 OPM-2 异种移植物中内在凋亡途径的剂量依赖性激活，如通过激活的 BAK、裂解的 caspase-3 和裂解的 PARP 所测量的，持续裂解PARP 和激活的 BAK 可在 12 小时内检测到，而裂解的 caspase-3 可在 24 小时内检测到。免疫组织化学分析表明，裂解的 caspase-3[3] 呈剂量依赖性增加。

实验参考方法 Experimental Reference Method

Cell experiment [1]:

Cell lines

C002M and C057M melanoma cell lines

Preparation Method

C002M and C057M were treated with the MCL1 inhibitor (AMG-176, 5 μM) for 72 hours and cell death was measured by Annexin V staining.

Reaction Conditions

AMG-176 5uM; 72h

Applications

AMG-176 has a weak ability to induce apoptosis in C002M melanoma cell line, but a strong ability to induce apoptosis in C057M melanoma cell line. AMG-176 has a synergistic effect with I-BET151 in these two melanoma cell lines.
Animal experiment [2]:

Animal models

Human MCL1 Knock-In Mice

Preparation Method

Ultiple myeloma cells (cell line OPM-2 luc) were injected s.c. in the right flank of mice (5 × 106 cells). Animals were randomized into groups (n = 10 per group). Animals were then orally administered with AMG-176 daily, 2×/week, or 1×/week.

Dosage form

10mg/kg;20 mg/kg;30 mg/kg; 60mg/kg. 2h-24h

Applications

Dose-dependent activation of the intrinsic apoptosis pathway in OPM-2 xenografts, as measured by activated BAK, cleaved caspase-3, and cleaved PARP, was detected as early as 2 hours after oral administration of AMG-176, with sustained cleaved PARP and activated BAK detectable through 12 hours and cleaved caspase-3 through 24 hours. Immunohistochemistry analysis revealed a similar dose-dependent increase in cleaved caspase-3.

References:

[1]. Tseng HY, Dreyer J, et,al.Co-targeting bromodomain and extra-terminal proteins and MCL1 induces synergistic cell death in melanoma. Int J Cancer. 2020 Oct 15;147(8):2176-2189. doi: 10.1002/ijc.33000. Epub 2020 Apr 24. PMID: 32249419.

[2]. Caenepeel S, Brown SP,et,al. AMG 176, a Selective MCL1 Inhibitor, Is Effective in Hematologic Cancer Models Alone and in Combination with Established Therapies. Cancer Discov. 2018 Dec;8(12):1582-1597. doi: 10.1158/2159-8290.CD-18-0387. Epub 2018 Sep 25. Erratum in: Cancer Discov. 2019 Jul;9(7):980. PMID: 30254093.

产品文档 Product Documents

Purity:>99.00%

化学性质Chemical Properties

CAS 号
1883727-34-1
同义词
AMG-176
SMILES
ClC1=CC=C2C(CCC[C@@]23CN(C[C@@](CC4)([H])[C@]4([H])[C@H](/C=C/C[C@H](C)[C@H]5C)OC)C6=CC(C(NS5(=O)=O)=O)=CC=C6OC3)=C1
分子式
C33H41ClN2O5S
分子量
613.21 g/mol
溶解性
Soluble in DMSO
保存条件
Store at -20&#176;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°C，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。

计算工具摩尔浓度 / 稀释 / 分子量 / 单位换算 / 体内配方 / 溶解度

g/mol