Description
Mertansine, the cytotoxic component in antibody-drug conjugates, is attached to a monoclonal antibody through reaction of the thiol group with the SPP (N-succinimidyl 4-(2-pyridyldithio)) linker or SMCC (4-(3-mercapto-2,5-dioxo-1 pyrrolidinylmethyl)-cylohexanecarboxylic acid) linkerto create an antibody-drug conjugate. It derives from a maytansine.
Synonyms
(14S,16S,33S,2R,4R,10E,12Z,14R)-86-chloro-14-hydroxy-85,14-dimethoxy-33,2,7,10-tetramethyl-12,6-dioxo-7-aza-1(6,4)-oxazinana-3(2,3)-oxirana-8(1,3)-benzenacyclotetradecaphane-10,12-dien-4-yl N-(3-mercaptopropanoyl)-N-methyl-L-alaninate; N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine; DM 1; Maytansinoid DM 1; N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)maytansine; DM-1; DM1; DM1 Compound; DM1 [Maytansinoid]
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
Canonical SMILES
CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)OC)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)N(C)C(=O)CCS)C)C)OC)(NC(=O)O2)O
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+/t20-,21+,25+,26-,27+,31+,34+,35+/m1/s1
InChIKey
ANZJBCHSOXCCRQ-FKUXLPTCSA-N
Solubility
Soluble in chloroform (slightly), methanol (slightly)
Melting Point
>168°C (dec.)
Flash Point
520.5±34.3 °C
Index Of Refraction
1.599
Vapor Pressure
0.0±0.3 mmHg at 25°C
In Vitro
Mertansine, a tubulin inhibitor, is used as the cytotoxic component of antibody-drug conjugates (ADCs) for cancer therapy. Mertansine potently inhibited UGT1A1-catalyzed SN-38 glucuronidation, UGT1A3-catalyzed chenodeoxycholic acid 24-acyl-β-glucuronidation, and UGT1A4-catalyzed trifluoperazine N-β-d-glucuronidation, with Ki values of 13.5 µM, 4.3 µM, and 21.2 µM, respectively, but no inhibition of UGT1A6, UGT1A9, and UGT2B7 enzyme activities was observed in human liver microsomes.
In Vivo
A 48 h treatment of mertansine (1.25-2500 nM) in human hepatocytes resulted in the dose-dependent suppression of mRNA levels of CYP1A2, CYP2B6, CYP3A4, CYP2C8, CYP2C9, CYP2C19, UGT1A1, and UGT1A9, with IC50 values of 93.7 109.1, 36.8 18.3, 160.6 167.4, 32.1 14.9, 578.4 452.0, 539.5 233.4, 856.7 781.9, and 54.1 29.1 nM, respectively, and decreased the activities of CYP1A2-mediated phenacetin O-deethylase, CYP2B6-mediated bupropion hydroxylase, and CYP3A4-mediated midazolam 1-hydroxylase.
Clinical Trial Information
NCT Number | Condition Or Disease | Phase | Start Date | Sponsor | Status |
NCT02254005 | Breast Neoplasms | Phase 1 | 2014-10-01 | Boehringer Ingelheim | Completed |
NCT02452554 | Pleuropulmonary Blastoma | Phase 2 | 2020-09-22 | Children's Oncology Group | Active, not recruiting |
NCT02420873 | Leukemia | Phase 2 | 2018-08-28 | M.D. Anderson Cancer Center | Completed |
NCT02254044 | Carcinoma, Squamous Cell | Phase 1 | 2014-10-01 | Boehringer Ingelheim | Terminated |
NCT02725541 | Breast Cancer | Phase 2 | 2016-09-14 | Jenny C. Chang, MD | Withdrawn (loss of funding support) |
Appearance
White to light yellow solid
Shelf Life
≥360 days if stored properly
Shipping
Room temperature
Storage
Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)
Pictograms
Corrosive; Acute Toxic; Health Hazard
Boiling Point
937.1±65.0 °C Press: 760 Torr