Description
DM 4 is an intermediate used to prepare semisynthetic maytansine analogs which can be conjugated with antibodies for the targeted treatment of cancer.
Synonyms
Ravtansine; N2'-Deacetyl-N2'-(4-mercapto-4-methyl-1-oxopentyl)-maytansine
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-(4-methyl-4-sulfanylpentanoyl)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)CCC(C)(C)S)C)C)OC)(NC(=O)O2)O
InChI
InChI=1S/C38H54ClN3O10S/c1-21-12-11-13-28(49-10)38(47)20-27(50-35(46)40-38)22(2)33-37(6,52-33)29(51-34(45)23(3)41(7)30(43)14-15-36(4,5)53)19-31(44)42(8)25-17-24(16-21)18-26(48-9)32(25)39/h11-13,17-18,22-23,27-29,33,47,53H,14-16,19-20H2,1-10H3,(H,40,46)/b13-11-,21-12+/t22-,23+,27+,28-,29-,33-,37+,38+/m1/s1
InChIKey
JFCFGYGEYRIEBE-YBVXEINESA-N
In Vitro
DM1 and DM4 inactivated CYP3A from human liver microsomes with K(i)/k(inact) values of 4.8 ± 0.9 μM/0.035 ± 0.002 min(-1) and 3.3 ± 0.2 μM/0.114 ± 0.002 min(-1), respectively. DM1 and DM4 inactivated recombinant CYP3A4 with K(i)/k(inact) values of 3.4 ± 1.0 μM/0.058 ± 0.005 min(-1) and 1.4 ± 0.3 μM/0.117 ± 0.006 min(-1), respectively. Because of instability in plasma, further characterization of the DM1 and DM4 intramolecular and intermolecular disulfide conjugates observed in vivo is required before an accurate drug-drug interaction (DDI) prediction can be made. AMCs with noncleavable thioether-linked DM1 as the cytotoxic agent are predicted to have no potential for a DDI with any of the major human P450s studied.
Clinical Trial Information
NCT Number | Condition Or Disease | Phase | Start Date | Sponsor | Status |
NCT03552471 | BRCA1 Gene Mutation | Phase 1 | 2021-08-13 | Ohio State University Comprehensive Cancer Center | Active, not recruiting |
NCT03455556 | Mesothelin Positive | Phase 1 | 2020-05-15 | Mayo Clinic | Terminated (slow accrual) |
NCT04606914 | Ovarian Cancer | Phase 2 | 2021-07-08 | University of Alabama at Birmingham | Recruiting |
NCT05071053 | Adenocarcinoma Gastric | Phase 2 | 2021-11-29 | Sanofi | Recruiting |
NCT04296890 | Epithelial Ovarian Cancer | Phase 3 | 2021-05-27 | ImmunoGen, Inc. | Active, not recruiting |
Shipping
-20°C (International: -20°C)
Pictograms
Corrosive; Acute Toxic; Irritant; Health Hazard