Mertansine is a potent microtubule-targeted compound that inhibits tubulin assembly into microtubules, with the KD value of 0.86µM [1]. Mertansine binds to the vinblastine-binding site in the mitochondrial region, leading to mitotic arrest and apoptosis-mediated cell death [2]. Mertansine has been extensively conjugated to antibodies via linkers containing disulfide bonds for highly efficient killing of cancer cells[3].
In vitro, Mertansine treatment for 72 hours significantly inhibited the proliferation of MCF7 cells with an IC50 value of 0.71nM[4]. Treatment with 2.5µM Mertansine for 48h significantly reduced CYP1A2, CYP2B6, and CYP3A4 mRNA levels in human hepatocytes[5].
References:
[1] Lopus M, Oroudjev E, Wilson L, et al. Maytansine and cellular metabolites of antibody-maytansinoid conjugates strongly suppress microtubule dynamics by binding to microtubules[J]. Molecular cancer therapeutics, 2010, 9(10): 2689-2699.
[2] Martin-Aubert S, Avrillon K, Tournier N, et al. Successful repositioning of mertansine for improved chemotherapy by combining a polymer prodrug approach and PET imaging[J]. Journal of Controlled Release, 2025, 378: 803-813.
[3] Lopus M. Antibody-DM1 conjugates as cancer therapeutics[J]. Cancer letters, 2011, 307(2): 113-118.
[4] Oroudjev E, Lopus M, Wilson L, et al. Maytansinoid-antibody conjugates induce mitotic arrest by suppressing microtubule dynamic instability[J]. Molecular cancer therapeutics, 2010, 9(10): 2700-2713.
[5] Choi W G, Park R, Kim D K, et al. Mertansine Inhibits mRNA Expression and Enzyme Activities of Cytochrome P450s and Uridine 5′-Diphospho-Glucuronosyltransferases in Human Hepatocytes and Liver Microsomes[J]. Pharmaceutics, 2020, 12(3): 220.
Mertansine是一种强效微管靶向化合物，可抑制微管蛋白组装形成微管，KD值为0.86µM[1]。Mertansine结合于线粒体区域的长春花碱结合位点，导致有丝分裂停滞及凋亡介导的细胞死亡[2]。Mertansine已广泛通过含二硫键的连接子与抗体偶联，以实现对癌细胞的高效杀伤[3]。
在体外，Mertansine处理72小时显著抑制了MCF7细胞的增殖，IC50值为0.71nM[4]。使用2.5µM的Mertansine处理人肝细胞48小时，显著降低了CYP1A2、CYP2B6和CYP3A4的mRNA水平[6]。