Title:
MAYTANSINE DERIVATIVE, SYNTHESIS METHOD THEREFOR AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/253794
Kind Code:
A1
Abstract:
The invention relates to a maytansine derivative, a synthesis method therefor and a use thereof. The invention constructs an integrative expression vector pSBT11-astC consisting an alanyl enzyme gene astC, realizing heterologous expression of the alanyl enzyme gene in a mutant strain of actinosynnema pretiosum. An alanylated modified maytansine derivative is separated and purified from a crude extract of the mutant strain of actinosynnema pretiosum that expresses alanyl enzyme. According to an in-vitro anti-tumor activity test, the IC50 values of the compound to human cervical cancer cell (HeLa), human colon cancer cell (HCT116) and human breast cancer cell (MDA-MB-231) are 3.1, 9.4 and 10.4nM respectively, thus, the compound can be used for preparing antineoplastic drugs and for forming antibody-drug conjugates with different antibodies and connexons.
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Inventors:
SHEN YUEMAO (CN)
LU CHUNHUA (CN)
LI XIAOMAN (CN)
LU CHUNHUA (CN)
LI XIAOMAN (CN)
Application Number:
PCT/CN2020/141335
Publication Date:
December 23, 2021
Filing Date:
December 30, 2020
Export Citation:
Assignee:
SHAN DONG UNIV (CN)
International Classes:
A61K31/537; C07D498/08; C12N15/74; C12P17/18
Foreign References:
| CN111635418A | 2020-09-08 |
Other References:
LI XIAOMAN: "Function-orientated Structure Optimizations of Bacterial Maytansinoids via Synthetic Biology", CHINA DOCTORAL DISSERTATIONS FULL-TEXT DATABASE, MEDICINE AND HEALTH SCIENCES, no. 2, 15 February 2020 (2020-02-15), XP055881374
LI SHANREN; LU CHUNHUA; CHANG XIAOYAN; SHEN YUEMAO: "Constitutive overexpression ofasm18increases the production and diversity of maytansinoids inActinosynnema pretiosum", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, SPRINGER BERLIN HEIDELBERG, BERLIN/HEIDELBERG, vol. 100, no. 6, 17 November 2015 (2015-11-17), Berlin/Heidelberg, pages 2641 - 2649, XP035870718, ISSN: 0175-7598, DOI: 10.1007/s00253-015-7127-7
LI SHANREN; LU CHUNHUA; CHANG XIAOYAN; SHEN YUEMAO: "Constitutive overexpression ofasm18increases the production and diversity of maytansinoids inActinosynnema pretiosum", APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, SPRINGER BERLIN HEIDELBERG, BERLIN/HEIDELBERG, vol. 100, no. 6, 17 November 2015 (2015-11-17), Berlin/Heidelberg, pages 2641 - 2649, XP035870718, ISSN: 0175-7598, DOI: 10.1007/s00253-015-7127-7
Attorney, Agent or Firm:
JINAN JINDI INTELLECTUAL PROPERTY AGENCY CO., LTD (CN)
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