Biological evaluation of 9-thioansamitocin P3.

Autor: Vasilevich NI; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China. Electronic address: nvasile2003@yahoo.com., Jiang H; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Xiao H; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Feng K; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Jian C; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Chen C; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Li M; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Chen Z; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Pang L; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Li X; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Chestkov AV; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China., Sun AH; Department of Pathology, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA70112, USA., Xu W; Department of Pathology, Tulane University Health Sciences Center, Tulane Cancer Center, New Orleans, LA70112, USA., Fuselier JA; Peptide Research Labs, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA., Coy DH; Peptide Research Labs, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA., Sun L; Shenzhen Academy of Peptide Targeting Technology at Pingshan and Shenzhen Tyercan Bio-Pharm Co., Ltd, Shenzhen, Guangdong, 518118, China; Peptide Research Labs, Department of Medicine, Tulane University Health Sciences Center, New Orleans, LA70112, USA. Electronic address: peptide612@gmail.com.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Feb 12; Vol. 696, pp. 149483. Date of Electronic Publication: 2024 Jan 09.
DOI: 10.1016/j.bbrc.2024.149483
Abstrakt: Highly cytotoxic maytansine derivatives are widely used in targeted tumor delivery. Structure-activity studies published earlier suggested the C9 carbinol to be a key element necessary to retain the potency. However, in 1984 a patent was published by Takeda in which the synthesis of 9-thioansamitocyn (AP3SH) was described and its activity in xenograft models was shown. In this article we summarize the results of an extended study of the anti-tumor properties of AP3SH. Like other maytansinoids, it induces apoptosis and arrests the cell cycle in the G2/M phase. It is metabolized in liver microsomes predominately by C3A4 isoform and doesn't inhibit any CYP isoforms except CYP3A4 (midazolam, IC50 7.84 μM). No hERG inhibition, CYP induction or mutagenicity in Ames tests were observed. AP3SH demonstrates high antiproliferative activity against 25 tumor cell lines and tumor growth inhibition in U937 xenograft model. Application of AP3SH as a cytotoxic payload in drug delivery system was demonstrated by us earlier.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sun L. reports financial support was provided by Shenzhen Science and Technology Program. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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