CAS: 2180923-05-9; (S)-N-((4-(((1,4-Dioxan-2-yl)Methyl)Amino)-3-Nitrophenyl)Sulfonyl)-2-((1H-Pyrrolo[2,3-B]Pyridin-5-yl)Oxy)-4-(4-((6-(4-Chlorophenyl)Spiro[3.5]Non-6-En-7-yl)Methyl)Piperazin-1-yl)Benzamide
该化合物是一种新颖的,口述生物可获得的小分子BCL-2抑制剂,旨在有选择地瞄准和扰乱BCL-2蛋白质的抗吸食活动.它通过对具有高度亲近性的BCL-2的约束,在癌症细胞中,特别是在依赖BCL-2生存的细胞中,促进流行性疾病.Lisafoclax表明与早期的BCL-2抑制剂相比,选择性程度有所提高,目标外影响减少,提高了治疗潜力.临床和临床研究表明,血解恶性恶性疾病,包括慢性淋巴细胞性白血病(CLLL)和急性类细胞性白血病(AML)的功效.其最优化的药性皮肤病特征允许灵活剂量疗法,而其可控制的安全特征则支持对混合疗法的进一步调查.Lisftoclax是定向癌症治疗的一个大有希望的进步.
- 英文名称(S)-N-((4-(((1,4-Dioxan-2-yl)Methyl)Amino)-3-Nitrophenyl)Sulfonyl)-2-((1H-Pyrrolo[2,3-B]Pyridin-5-yl)Oxy)-4-(4-((6-(4-Chlorophenyl)Spiro[3.5]Non-6-En-7-yl)Methyl)Piperazin-1-yl)Benzamide
- 中文名称(S)-N-((4-(((1,4-二恶烷-2-基)甲基)氨基)-3-硝基苯基)磺酰基)-2-((1H-B[2,3-B]吡啶-5-基)氧基)-4-(4-((6-(4-氯苯基).[3.5]壬烷-6-烯-7-基)甲基)哌嗪-1-基)苯甲酰胺
- IUPAC名称(S)-N-((4-(((1,4-dioxan-2-yl)methyl)amino)-3-nitrophenyl)sulfonyl)-2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((6-(4-chlorophenyl)spiro[3.5]non-6-en-7-yl)methyl)piperazin-1-yl)benzamide
- 其它别名Bcl-2/bcl-Xl Inhibitor 1; Lisaftoclax; Benzamide, 4-[4-[[6-(4-Chlorophenyl)Spiro[3.5]Non-6-En-7-Yl]Methyl]-1-Piperazinyl]-N-[[4-[[(2S)-1,4-Dioxan-2-Ylmethyl]Amino]-3-Nitrophenyl]Sulfonyl]-2-(1H-Pyrrolo[2,3-B]Pyridin-5-Yloxy)-; (S)-N-((4-(((1,4-Dioxan-2-yl)Methyl)Amino)-3-Nitrophenyl)Sulfonyl)-2-((1H-Pyrrolo[2,3-B]Pyridin-5-yl)Oxy)-4-(4-((6-(4-Chlorophenyl)Spiro[3.5]Non-6-En-7-yl)Methyl)Piperazin-1-yl)Benzamide; Lisaftoclax, 10 Mm In Dmso
- CAS编号2180923-05-9
- MFCD编号:MFCD34469554
- FDA UNII编号:OSL3FEZ1IF
- 分子式:C45H48ClN7O8S分子量:882.44
- 产品CID: 1135692
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海关参考信息
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主要参考文献
1: Luo F, Li H, Ma W, Cao J, Chen Q, Lu F, Qiu M, Zhou P, Xia Z, Zeng K, Zhan J, Zhou T, Luo Q, Pan W, Zhang L, Lin C, Huang Y, Zhang L, Yang D, Zhao H. The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype, promoting a favorable response to anti-PD-1 therapy via NLRP3 activation. Cell Mol Immunol. 2024 Jan;21(1):60-79. doi: 10.1038/s41423-023-01112-y. Epub 2023 Dec 7.
2: Ailawadhi S, Chen Z, Huang B, Paulus A, Collins MC, Fu LT, Li M, Ahmad M, Men L, Wang H, Davids MS, Liang E, Mekala DJ, He Z, Lasica M, Yannakou CK, Parrondo R, Glass L, Yang D, Chanan-Khan A, Zhai Y. Novel BCL-2 Inhibitor Lisaftoclax in Relapsed or Refractory Chronic Lymphocytic Leukemia and Other Hematologic Malignancies: First-in-Human Open-Label Trial. Clin Cancer Res. 2023 Jul 5;29(13):2385-2393. doi: 10.1158/1078-0432.CCR-22-3321.
3: Zhai Y, Tang Q, Fang DD, Deng J, Zhang K, Wang Q, Yin Y, Fu C, Xue SL, Li N, Zhou F, Yang D. Lisaftoclax in Combination with Alrizomadlin Overcomes Venetoclax Resistance in Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia: Preclinical Studies. Clin Cancer Res. 2023 Jan 4;29(1):183-196. doi: 10.1158/1078-0432.CCR-22-0978. 28(24):5455-5468. doi: 10.1158/1078-0432.CCR-21-4037. 20(1):299. doi: 10.1186/s12967-022-03497-2.
合成参考文献
参考文献:10.1021/acs.jmedchem.4c00027
摘要:Guo Y, Xue H, Hu N, Liu Y, Sun H, Yu D, Qin L, Shi G, Wang F, Xin L, Sun W, Zhang F, Song X, Li S, Wei Q, Guo Y, Li Y, Liu X, Chen S, Zhang T, Wu Y, Su D, Zhu Y, Xu A, Xu H, Yang S, Zheng Z, Liu J, Yang X, Yuan X, Hong Y, Sun X, Guo Y, Zhou C, Liu X, Wang L, Wang Z. Discovery of the Clinical Candidate Sonrotoclax (BGB-11417), a Highly Potent and Selective Inhibitor for Both WT and G101V Mutant Bcl-2. J. Med. Chem. 2024 May 02;67(10):7836–58. doi: 10.1021/acs.jmedchem.4c00027.
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