(R)-(-)-Gossypol acetic acid (AT-101 (acetic acid))
(Synonyms: (R)-(-)-醋酸棉酚; AT-101 (acetic acid); (-)-Gossypol acetic acid; (R)-Gossypol acetic acid) 目录号 : GC34096
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(R)-(-)-Gossypol acetic acid (AT-101 (acetic acid))是一种新型的、具有口服活性的Bcl-2家族蛋白抑制剂，可抑制Bcl-2（Ki=260±30nM），Mcl-1（Ki=170±10nM）和Bcl-xL（Ki=480±40nM）。
Cas No.:866541-93-7
Sample solution is provided at 25 µL, 10mM.
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(R)-(-)-Gossypol acetic acid (AT-101 (acetic acid)) is a novel, orally active Bcl-2 family protein inhibitor that inhibits Bcl-2 (Ki=260±30nM), Mcl-1 (Ki=170±10nM), and Bcl-xL (Ki=480±40nM)[1-2]. (R)-(-)-Gossypol acetic acid can be used in research related to glioblastoma, chronic lymphocytic leukemia, and non-small cell lung cancer, among others[3-4].
In vitro, (R)-(-)-Gossypol acetic acid (2.5–15μM) was co-treated with Trastuzumab in SKBR-3 and MDA-MB-453 HER2-positive breast cancer cells for 72 hours. (R)-(-)-Gossypol acetic acid induced apoptosis by inhibiting the PI3K/AKT signaling pathway[5]. (R)-(-)-Gossypol acetic acid (15μM) was used to treat U87MG and U343 glioma cells for 48 hours. (R)-(-)-Gossypol acetic acid induced mitophagic cell death[6].
In vivo, (R)-(-)-Gossypol acetic acid (35mg/kg) combined with Gefitinib (50mg/kg) was administered orally five times per week to BALB/c nude mice subcutaneously inoculated with PC-9-GR cells (harboring the EGFR T790M mutation). The combination of (R)-(-)-Gossypol acetic acid and Gefitinib significantly inhibited tumor growth and increased the expression of the apoptosis marker cleaved caspase-3 in tumor tissues[7]. (R)-(-)-Gossypol acetic acid (50mg/kg) was administered via daily intraperitoneal injection, five times per week, to NOD/SCID mice subcutaneously inoculated with U937 human leukemia cells for 60 days. (R)-(-)-Gossypol acetic acid significantly inhibited tumor growth and induced tumor cell apoptosis[8].
References:
[1] Oliver CL, Bauer JA, Wolter KG, et al. In vitro effects of the BH3 mimetic, (-)-gossypol, on head and neck squamous cell carcinoma cells. Clin Cancer Res. 2004 Nov 15;10(22):7757-63.
[2] Sun Y, Wu J, Aboukameel A, et al. Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther. 2008 Sep;7(9):1418-26.
[3] Baggstrom MQ, Qi Y, Koczywas M, et al. A phase II study of AT-101 (Gossypol) in chemotherapy-sensitive recurrent extensive-stage small cell lung cancer. J Thorac Oncol. 2011 Oct;6(10):1757-60.
[4] Schelman WR, Mohammed TA, Traynor AM, et al. A phase I study of AT-101 with cisplatin and etoposide in patients with advanced solid tumors with an expanded cohort in extensive-stage small cell lung cancer. Invest New Drugs. 2014 Apr;32(2):295-302.
[5] Bulut G, Atmaca H, Karaca B. Trastuzumab in combination with AT-101 induces cytotoxicity and apoptosis in Her2 positive breast cancer cells. Future Oncol. 2020 Jan;16(3):4485-4495.
[6] Meyer N, Zielke S, Michaelis JB, et al. AT 101 induces early mitochondrial dysfunction and HMOX1 (heme oxygenase 1) to trigger mitophagic cell death in glioma cells. Autophagy. 2018;14(10):1693-1709.
[7] Zhao R, Zhou S, Xia B, et al. AT-101 enhances gefitinib sensitivity in non-small cell lung cancer with EGFR T790M mutations. BMC Cancer. 2016 Jul 18;16:491.
[8] Li G, Liu L, Shan C, et al. RhoA/ROCK/PTEN signaling is involved in AT-101-mediated apoptosis in human leukemia cells in vitro and in vivo. Cell Death Dis. 2014 Jan 16;5(1):e998. doi: 10.1038/cddis.2013.519. Erratum in: Cell Death Dis. 2025 Apr 3;16(1):243.
(R)-(-)-Gossypol acetic acid (AT-101 (acetic acid))是一种新型的、具有口服活性的Bcl-2家族蛋白抑制剂，可抑制Bcl-2（Ki=260±30nM），Mcl-1（Ki=170±10nM）和Bcl-xL（Ki=480±40nM）[1-2]。(R)-(-)-Gossypol acetic acid可用于胶质母细胞瘤、慢性淋巴细胞白血病和非小细胞肺癌等的相关研究[3-4]。
在体外，(R)-(-)-Gossypol acetic acid（2.5–15μM）与曲妥珠单抗（Trastuzumab）联合处理SKBR-3和MDA-MB-453 HER2阳性乳腺癌细胞72小时。(R)-(-)-Gossypol acetic acid通过抑制PI3K/AKT信号通路诱导细胞凋亡[5]。(R)-(-)-Gossypol acetic acid（15μM）处理U87MG和U343胶质瘤细胞48小时。(R)-(-)-Gossypol acetic acid诱导线粒体自噬性细胞死亡[6]。
在体内，(R)-(-)-Gossypol acetic acid（35mg/kg）联合Gefitinib（50mg/kg）每周五次口服给药，用于处理皮下接种了PC-9-GR细胞（具有EGFR T790M突变）的BALB/c裸鼠。(R)-(-)-Gossypol acetic acid联合Gefitinib显著抑制了肿瘤生长，并增加了肿瘤组织中的细胞凋亡标志物（cleaved caspase-3）表达[7]。(R)-(-)-Gossypol acetic acid（50mg/kg）每日腹腔注射，每周五次，用于处理皮下接种了U937人白血病细胞的NOD/SCID小鼠，持续60天。(R)-(-)-Gossypol acetic acid显著抑制了肿瘤生长并诱导了肿瘤细胞凋亡[8]。
| Cell experiment [1]: | |
Cell lines | U87MG and U343 human glioma cells |
Preparation Method | U87MG and U343 cells were treated with (R)-(-)-Gossypol acetic acid (15µM). |
Reaction Conditions | 15µM; 48h. |
Applications | (R)-(-)-Gossypol acetic acid treatment induced a robust decrease in mitochondrial protein clusters, triggered early mitochondrial membrane depolarization, and promoted the engulfment of mitochondria within autophagosomes. This mitophagic cell death was dependent on autophagy (ATG5) and the mitophagy receptors (BNIP3/BNIP3L), and was driven by the upregulation of HMOX1 (heme oxygenase 1). |
| Animal experiment [2]: | |
Animal models | NOD/SCID mice |
Preparation Method | Mice were subcutaneously inoculated with U937 human leukemia cells. Five days after tumor inoculation, mice received daily intraperitoneal injections of (R)-(-)-Gossypol acetic acid (50mg/kg) for 60 days. |
Dosage form | 50mg/kg; i.p.; five times per week. |
Applications | (R)-(-)-Gossypol acetic acid treatment significantly inhibited tumor growth and induced apoptosis in U937 xenografts, as evidenced by TUNEL assay and increased immunoreactivity for cleaved caspase-3 and PARP. This antileukemic activity was associated with the activation of the RhoA/ROCK1/PTEN signaling pathway and the inactivation of Akt in vivo. |
References: | |
| Cas No. | 866541-93-7 | SDF | |
| 别名 | (R)-(-)-醋酸棉酚; AT-101 (acetic acid); (-)-Gossypol acetic acid; (R)-Gossypol acetic acid | ||
| Canonical SMILES | OC1=C2C(C=O)=C(O)C(O)=C(C(C)C)C2=CC(C)=[C@]1[C@]3=C(C)C=C4C(C(C)C)=C(O)C(O)=C(C=O)C4=C3O.CC(O)=O.[R] | ||
| 分子式 | C32H34O10 | 分子量 | 578.61 |
| 溶解度 | DMSO : 39.33 mg/mL (67.97 mM) | 储存条件 | Store at -20°C, protect from light, stored under nitrogen |
| 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。 |
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| 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。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.7283 mL | 8.6414 mL | 17.2828 mL |
| 5 mM | 345.7 μL | 1.7283 mL | 3.4566 mL |
| 10 mM | 172.8 μL | 864.1 μL | 1.7283 mL |
| 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 | 只 |
| 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 | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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