DM1-SMe - CAS 138148-68-2

DM1-SMe - CAS 138148-68-2 Catalog number: BADC-00020

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DM1-SMe is a potent maytansinoid microtubular inhibitor and an unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group. DM1-SMe can be readily conjugate to the SH group of an antibody to form antibody-drug conjugate (ADC). .

Category
ADCs Cytotoxin with Linkers
Product Name
DM1-SMe
CAS
138148-68-2
Catalog Number
BADC-00020
Molecular Formula
C36H50ClN3O10S2
Molecular Weight
784.38
DM1-SMe

Ordering Information

Catalog Number Size Price Quantity
BADC-00020 25 mg $499
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Description
DM1-SMe is a potent maytansinoid microtubular inhibitor and an unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group. DM1-SMe can be readily conjugate to the SH group of an antibody to form antibody-drug conjugate (ADC). .
Synonyms
DM1-SMe; DM1-SSMe; maytansinoid derivative with ADC linker. Maytansine or mertansine or emtansine derivative; N2'-deacetyl-N2'-[3-(methyldithio)-1-oxopropyl]maytansine.
IUPAC Name
[(1S,2R,3S,5S,6S,16Z,18Z,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-(methyldisulfanyl)propanoyl]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)CCSSC)C)C)OC)(NC(=O)O2)O
InChI
InChI=1S/C36H50ClN3O10S2/c1-20-11-10-12-27(47-8)36(45)19-26(48-34(44)38-36)21(2)32-35(4,50-32)28(49-33(43)22(3)39(5)29(41)13-14-52-51-9)18-30(42)40(6)24-16-23(15-20)17-25(46-7)31(24)37/h10-12,16-17,21-22,26-28,32,45H,13-15,18-19H2,1-9H3,(H,38,44)/b12-10-,20-11-/t21-,22+,26+,27-,28+,32+,35+,36+/m1/s1
InChIKey
ZLUUPZXOPGORNG-UDXCHANISA-N
Solubility
Soluble in DMSO, not in water
In Vitro
Structure-activity-relationship studies had identified the C3 ester side chain as a critical element for antitumor activity of maytansinoids. The maytansinoids bearing the methyl group at C3 position with D configuration were about 100 to 400-fold less cytotoxic than their corresponding L-epimers toward various cell lines. IMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM to 0.1 µM and 0.3 pM to 3 nM, respectively. IMGN901 was tested against a subset of PPTP solid tumor xenografts focusing on those with high CD56 expression.The combination of IMGN901 with topotecan was also evaluated.
In Vivo
Neuroblastoma models expressed CD56 at or above the median expression level for all PPTP xenografts and cell lines. Neuroblastoma cell lines demonstrated relatively low sensitivity to DM1-SMe compared to other cell lines, but the sensitivity of neuroblastoma cell lines to IMGN901 was comparable to that of non-neuroblastoma cell lines. In vivo, objective responses were observed in 9 of 24 (38%) models including, three of seven neuroblastoma xenografts, and two of seven rhabdomyosarcoma xenografts. All xenografts with objective responses showed homogeneous high-level staining by IHC for CD56, but not all xenografts with homogenous high-level staining had objective responses. Combined with topotecan, IMGN901 demonstrated therapeutic enhancement against two of four neuroblastoma models.
Appearance
Soild powder
Purity
≥98%
Shelf Life
2 years if stored properly
Shipping
Room temperature
Storage
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
1.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.
BACKGROUND: ;IMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and that is conjugated to the maytansinoid, DM1 (a microtubule targeting agent).;PROCEDURES: ;IMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01 nM to 0.1 µM and 0.3 pM to 3 nM, respectively. IMGN901 was tested against a subset of PPTP solid tumor xenografts focusing on those with high CD56 expression.The combination of IMGN901 with topotecan was also evaluated.;RESULTS: ;Neuroblastoma models expressed CD56 at or above the median expression level for all PPTP xenografts and cell lines. Neuroblastoma cell lines demonstrated relatively low sensitivity to DM1-SMe compared to other cell lines, but the sensitivity of neuroblastoma cell lines to IMGN901 was comparable to that of non-neuroblastoma cell lines. In vivo, objective responses were observed in 9 of 24 (38%) models including, three of seven neuroblastoma xenografts, and two of seven rhabdomyosarcoma xenografts. All xenografts with objective responses showed homogeneous high-level staining by IHC for CD56, but not all xenografts with homogenous high-level staining had objective responses.

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This equation is commonly abbreviated as: C1V1 = C2V2

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