艾贝司他

艾贝司他（INN^[1]：Abexinostat，前身为PCI-24781），也译为阿贝司他，是一种用于癌症治疗的实验性候选药物。^[2]它由法莫斯利医药（Pharmacyclics）开发并授权给徐诺药业，并且正在进行B细胞淋巴瘤的II期临床试验。^[3]临床前研究表明它还具有治疗不同类型癌症的潜力。^[4][5][6][7]

艾贝司他
IUPAC名 3-[(Dimethylamino)methyl]-N2-[4-(hydroxycarbamoyl)phenoxy]ethyl1-benzofuran-2-carboxamide
别名	PCI-24781; CRA-024781
识别
CAS号	783355-60-2  Y 783356-67-2（(HCl)）  Y
PubChem	11749858
ChemSpider	9924562
SMILES	O=C(NO)c3ccc(OCCNC(=O)c2oc1ccccc1c2CN(C)C)cc3
InChI	1/C21H23N3O5/c1-24(2)13-17-16-5-3-4-6-18(16)29-19(17)21(26)22-11-12-28-15-9-7-14(8-10-15)20(25)23-27/h3-10,27H,11-13H2,1-2H3,(H,22,26)(H,23,25)
InChIKey	MAUCONCHVWBMHK-UHFFFAOYAM
KEGG	D10060
性质
化学式	C21H23N3O5
摩尔质量	397.42 g·mol−1
若非注明，所有数据均出自标准状态（25 ℃，100 kPa）下。

艾贝司他作为一种泛组蛋白脱乙酰酶抑制剂发挥其作用^[8][9]并抑制RAD51，后者参与修复DNA双链断裂。^[10]

参考资料

1. WHO Drug Information （页面存档备份，存于互联网档案馆）, Vol. 25, No. 2, 2011
2. Abexinostat （页面存档备份，存于互联网档案馆）, NCI Cancer Dictionary
3. Abexinostat HCl (PCI-24781), PanHDAC-inhibitor 互联网档案馆的存档，存档日期2013-10-27., Pharmacyclics
4. Bhalla, S; Balasubramanian, S; David, K; Sirisawad, M; Buggy, J; Mauro, L; Prachand, S; Miller, R; Gordon, LI; Evens, AM. PCI-24781 induces caspase and reactive oxygen species-dependent apoptosis through NF-kappaB mechanisms and is synergistic with bortezomib in lymphoma cells. Clinical Cancer Research. 2009, 15 (10): 3354–65. PMC 2704489 . PMID 19417023. doi:10.1158/1078-0432.CCR-08-2365.
5. Lopez, G; Liu, J; Ren, W; Wei, W; Wang, S; Lahat, G; Zhu, QS; Bornmann, WG; McConkey, DJ; Pollock, RE; Lev, DC. Combining PCI-24781, a novel histone deacetylase inhibitor, with chemotherapy for the treatment of soft tissue sarcoma. Clinical Cancer Research. 2009, 15 (10): 3472–83. PMID 19417021. doi:10.1158/1078-0432.CCR-08-2714 .
6. Rivera-Del Valle, N; Gao, S; Miller, CP; Fulbright, J; Gonzales, C; Sirisawad, M; Steggerda, S; Wheler, J; Balasubramanian, S; Chandra, J. PCI-24781, a Novel Hydroxamic Acid HDAC Inhibitor, Exerts Cytotoxicity and Histone Alterations via Caspase-8 and FADD in Leukemia Cells. International Journal of Cell Biology. 2010, 2010: 207420. PMC 2817379 . PMID 20145726. doi:10.1155/2010/207420 .
7. Yang, C; Choy, E; Hornicek, FJ; Wood, KB; Schwab, JH; Liu, X; Mankin, H; Duan, Z. Histone deacetylase inhibitor (HDACI) PCI-24781 potentiates cytotoxic effects of doxorubicin in bone sarcoma cells. Cancer Chemotherapy and Pharmacology. 2011, 67 (2): 439–46. PMID 20461381. S2CID 1344662. doi:10.1007/s00280-010-1344-7.
8. Buggy, JJ; Cao, ZA; Bass, KE; Verner, E; Balasubramanian, S; Liu, L; Schultz, BE; Young, PR; Dalrymple, SA. CRA-024781: A novel synthetic inhibitor of histone deacetylase enzymes with antitumor activity in vitro and in vivo. Molecular Cancer Therapeutics. 2006, 5 (5): 1309–17. PMID 16731764. doi:10.1158/1535-7163.MCT-05-0442 .
9. Adimoolam, S; Sirisawad, M; Chen, J; Thiemann, P; Ford, JM; Buggy, JJ. HDAC inhibitor PCI-24781 decreases RAD51 expression and inhibits homologous recombination. Proceedings of the National Academy of Sciences of the United States of America. 2007, 104 (49): 19482–7. Bibcode:2007PNAS..10419482A. PMC 2148315 . PMID 18042714. doi:10.1073/pnas.0707828104 .
10. NCI Drug Dictionary. National Cancer Institute. [2023-02-02]. （原始内容存档于2023-02-02） （英语）.

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