Medical application of glufosfamide to resisting cancer

Abstract

Glufosfamide or an analogue thereof has specific restraining effects on cells having particular gene variation, and specifically can repair damaged cells through DNA. The cells or tissue at least has one gene mutation or more gene mutations in BRCA1, BRCA2, FANCD1, FANCD2, ATM, ATR, CHEK1, CHEK2, CTP, BARD1, BRIP1, PALB2, RAD51D, RAD51C, RAD52, RAD54, RAD55, RAD57, FAM175, NBN, Rad50, MER11, p53, NBS1, XRS2, XRCC2, XRCC3, ERCC1, ERCC2, ERCC3, ERCC4, XRCC1, Ku80, MHS6, MGMT, PARP or ERCC5. The analogue refers to an ester which is obtained through an esterification reaction on one or more hydroxyls in glufosfamide molecules and organic acid and inorganic oxygen acid, an ester which is obtained through an esterification reaction of one or more hydroxyls in the glufosfamide molecules and amino acids, and salt which is obtained through a reaction of the glufosfamide molecules and acid. The invention provides a medical application of the glufosfamide or the analogue thereof to treatment of tumor and cancer diseases of cancer patients having particular gene variation.

Description

technical field [0001] The present invention relates to glufosfamide, especially the treatment of glufosfamide to cancer or tumor patients with specific gene mutation. Background technique [0002] Glufosfamide (glufosfamide), the chemical name is β-D-glucopyranosyl-N, N'-bis (2-chloroethyl) phosphoramide, and the English name is β-D-Glucopyranosyl-[N, N'- bis[(2-chloroethyl)]phosphoric aciddiamide, a new type of alkylating agent antineoplastic drug, is formed by linking a molecule of isophosphoramide mustard with direct alkylation and a molecule of glucose through glycosidic bonds . Glufosfamide is transported into tumor cells by the sodium-dependent glucose transmembrane transporter SAAT1, and then hydrolyzed by glucosidase to release isophosphoramide mustard to exert its activity. . [0003] The compound was first developed by Asta Medica (Degussa) in Heidelberg, Germany, in cooperation with the Cancer Research Center (DKFZ). In October 2001, Baxter International Baxt...

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[0004] US Threshold company obtained the US FDA's fast-track approval qualification in 2004 for the treatment of unresectable locally advanced or metastatic pancreatic cancer that has previously received gemcitabine (W.Steve Ammons, Jin-Wei Wang y, Zhijian Yang y, George F.Tidmarshz and Robert M.Hoffmany, Neoplasia, 2007.8,9(8):625-633), but in 2007 the company announced that there was no significant increase in phase III clinical trials for patients with metastatic pancreatic cancer as second-line treatment Overall survival (Tudor E. Ciuleanua, Alexander V. Pavlovskyb, Gyorgy Bodokyc, Avgust M. Garind, Virginia K. Langmuire, Stewart Krolle, George T. Tidmarshe, A randomized Phase III trial of glufosfamide compared with best supportive care in metastatic revicarly no treated with gemcitabine, European Journal Of Cancer, 45(2009):1589-1596), that is, the subsequent development of the drug ended in failure because the final phase III clinical trial failed

[0005] In China, Qilu Pharmaceutical Co., Ltd. and Jiangsu Hansoh Pharmaceutical Co., Ltd. also applied for new drugs in 2005, and obtained approval from China Food and Drug Administration. However, there was no subsequent development and listing

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