Mertansine

• CAT Number: I001514
• CAS Number: 139504-50-0
• Molecular Formula: C35H48ClN3O10S
• Molecular Weight: 738.3
• Purity: ≥95%
• Target: microtubule inhibitor
• Solubility: 10 mM in DMSO
• Storage: -20°C
• IUPAC Name: [(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-21-hydroxy-12,20-dimethoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] (2S)-2-[methyl(3-sulfanylpropanoyl)amino]propanoate
• InChI: InChI=1S/C35H48ClN3O10S/c1-19-10-9-11-26(46-8)35(44)18-25(47-33(43)37-35)20(2)31-34(4,49-31)27(48-32(42)21(3)38(5)28(40)12-13-50)17-29(41)39(6)23-15-22(14-19)16-24(45-7)30(23)36/h9-11,15-16,20-21,25-27,31,44,50H,12-14,17-18H2,1-8H3,(H,37,43)/b11-9-,19-10+
• InChIKey: ANZJBCHSOXCCRQ-FKUXLPTCSA-N
• SMILES: C[C@@]1([C@@H](O1)[C@H](C)[C@]([H])(C[C@](N2)(O)[C@]([H])(OC)/C=C/C=C(CC3=CC(OC)=C(Cl)C4=C3)C)OC2=O)[C@@]([H])(OC([C@@H](N(C)C(CCS)=O)C)=O)CC(N4C)=O

Mertansine, also known as DM1 (CAT: I001514), is a cytotoxic compound and a potent microtubule-disrupting agent. It is a derivative of maytansine, a natural compound originally isolated from the Maytenus genus of plants. Mertansine has shown significant anticancer activity and is used as a cytotoxic payload in antibody-drug conjugates (ADCs) for targeted cancer therapy. In ADCs, mertansine is conjugated to a monoclonal antibody that specifically recognizes and binds to cancer cells expressing a specific antigen. Upon binding, the ADC is internalized by the cancer cell, and mertansine is released, exerting its cytotoxic effect by disrupting microtubule formation and causing cell cycle arrest and apoptosis. Mertansine-based ADCs have been approved for the treatment of certain types of breast cancer and are being investigated for their efficacy against other malignancies as well.

Reference

1:Phase 1/2 Study of the CD56-Targeting Antibody-Drug Conjugate Lorvotuzumab Mertansine (IMGN901) in Combination With Carboplatin/Etoposide in Small-Cell Lung Cancer Patients With Extensive-Stage Disease. Socinski MA, Kaye FJ, Spigel DR, Kudrik FJ, Ponce S, Ellis PM, Majem M, Lorigan P, Gandhi L, Gutierrez ME, Nepert D, Corral J, Ares LP.Clin Lung Cancer. 2017 Jan;18(1):68-76.e2. doi: 10.1016/j.cllc.2016.09.002. Epub 2016 Oct 3. PMID: 28341109 Free Article
2:αvβ3 Integrin-targeted reduction-sensitive micellar mertansine prodrug: Superb drug loading, enhanced stability, and effective inhibition of melanoma growth in vivo. Zhong P, Meng H, Qiu J, Zhang J, Sun H, Cheng R, Zhong Z.J Control Release. 2016 Dec 14. pii: S0168-3659(16)31259-7. doi: 10.1016/j.jconrel.2016.12.011. [Epub ahead of print] PMID: 27986551
3:Glutathione-Sensitive Hyaluronic Acid-SS-Mertansine Prodrug with a High Drug Content: Facile Synthesis and Targeted Breast Tumor Therapy. Zhong P, Zhang J, Deng C, Cheng R, Meng F, Zhong Z.Biomacromolecules. 2016 Nov 14;17(11):3602-3608. Epub 2016 Oct 21. PMID: 27723970
4:Lorvotuzumab mertansine, a CD56-targeting antibody-drug conjugate with potent antitumor activity against small cell lung cancer in human xenograft models. Whiteman KR, Johnson HA, Mayo MF, Audette CA, Carrigan CN, LaBelle A, Zukerberg L, Lambert JM, Lutz RJ.MAbs. 2014 Mar-Apr;6(2):556-66. doi: 10.4161/mabs.27756. Epub 2014 Jan 8. PMID: 24492307 Free PMC Article
5:Lorvotuzumab mertansine: antibody-drug-conjugate for CD56+ multiple myeloma. Berdeja JG.Front Biosci (Landmark Ed). 2014 Jan 1;19:163-70. Review. PMID: 24389179
6:Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab mertansine), by the pediatric preclinical testing program. Wood AC, Maris JM, Gorlick R, Kolb EA, Keir ST, Reynolds CP, Kang MH, Wu J, Kurmasheva RT, Whiteman K, Houghton PJ, Smith MA.Pediatr Blood Cancer. 2013 Nov;60(11):1860-7. doi: 10.1002/pbc.24647. Epub 2013 Jun 24. PMID: 23798344 Free PMC Article
7:Combined treatment of the immunoconjugate bivatuzumab mertansine and fractionated irradiation improves local tumour control in vivo. Gurtner K, Hessel F, Eicheler W, Dörfler A, Zips D, Heider KH, Krause M, Baumann M.Radiother Oncol. 2012 Mar;102(3):444-9. doi: 10.1016/j.radonc.2011.10.013. Epub 2011 Nov 17. PMID: 22100655
8:Cantuzumab mertansine in a three-times a week schedule: a phase I and pharmacokinetic study. Rodon J, Garrison M, Hammond LA, de Bono J, Smith L, Forero L, Hao D, Takimoto C, Lambert JM, Pandite L, Howard M, Xie H, Tolcher AW.Cancer Chemother Pharmacol. 2008 Oct;62(5):911-9. doi: 10.1007/s00280-007-0672-8. Epub 2008 Feb 27. PMID: 18301896
9:Phase I trial with the CD44v6-targeting immunoconjugate bivatuzumab mertansine in head and neck squamous cell carcinoma. Riechelmann H, Sauter A, Golze W, Hanft G, Schroen C, Hoermann K, Erhardt T, Gronau S.Oral Oncol. 2008 Sep;44(9):823-9. doi: 10.1016/j.oraloncology.2007.10.009. Epub 2008 Jan 18. PMID: 18203652
10:Safety and pharmacokinetics of bivatuzumab mertansine in patients with CD44v6-positive metastatic breast cancer: final results of a phase I study. Rupp U, Schoendorf-Holland E, Eichbaum M, Schuetz F, Lauschner I, Schmidt P, Staab A, Hanft G, Huober J, Sinn HP, Sohn C, Schneeweiss A.Anticancer Drugs. 2007 Apr;18(4):477-85. PMID: 17351401