sulfo-SPDB-DM4 - CAS 1626359-59-8

sulfo-SPDB-DM4 - CAS 1626359-59-8 Catalog number: BADC-00018

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DM4 with a reactive linker sulfo-SPDB, which can react with antibody to make antibody drug conjugate. DM4 can bind to tubulin at or near the vinblastine-binding site.

General Information

Category
ADCs Cytotoxin with Linkers
Product Name
sulfo-SPDB-DM4
CAS
1626359-59-8
Catalog Number
BADC-00018
Molecular Formula
C46H63ClN4O17S3
Molecular Weight
1075.66

Chemical Structure

  • sulfo-SPDB-DM4
Purity
≥98%
Appearance
Soild powder
Synonyms
Maytansinoid DM4- succinimidyl 4-(N-maleimidomethyl)cyclohexane-3-sulfo-carboxylate
Solubility
DMSO
Storage
Store in a cool and dry place (or refer to the Certificate of Analysis).
Density
1.44±0.1 g/cm3
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)SSCCC(C(=O)ON5C(=O)CCC5=O)S(=O)(=O)O)C)C)OC)(NC(=O)O2)O
InChI Key
ACJLJPQSHWOFQD-SKUWBIDSSA-N
InChI
1S/C46H63ClN4O17S3/c1-25-12-11-13-33(64-10)46(59)24-31(65-43(58)48-46)26(2)40-45(6,67-40)34(23-38(55)50(8)29-21-28(20-25)22-30(63-9)39(29)47)66-41(56)27(3)49(7)35(52)16-18-44(4,5)70-69-19-17-32(71(60,61)62)42(57)68-51-36(53)14-15-37(51)54/h11-13,21-22,26-27,31-34,40,59H,14-20,23-24H2,1-10H3,(H,48,58)(H,60,61,62)/b13-11+,25-12+/t26-,27+,31+,32?,33-,34+,40+,45+,46+/m1/s1
1.Effects of Drug-Antibody Ratio on Pharmacokinetics, Biodistribution, Efficacy, and Tolerability of Antibody-Maytansinoid Conjugates.
Sun X;Ponte JF;Yoder NC;Laleau R;Coccia J;Lanieri L;Qiu Q;Wu R;Hong E;Bogalhas M;Wang L;Dong L;Setiady Y;Maloney EK;Ab O;Zhang X;Pinkas J;Keating TA;Chari R;Erickson HK;Lambert JM Bioconjug Chem. 2017 May 17;28(5):1371-1381. doi: 10.1021/acs.bioconjchem.7b00062. Epub 2017 Apr 13.
Antibody-drug conjugates (ADCs) are being actively pursued as a treatment option for cancer following the regulatory approval of brentuximab vedotin (Adcetris) and ado-trastuzumab emtansine (Kadcyla). ADCs consist of a cytotoxic agent conjugated to a targeting antibody through a linker. The two approved ADCs (and most ADCs now in the clinic that use a microtubule disrupting agent as the payload) are heterogeneous conjugates with an average drug-to-antibody ratio (DAR) of 3-4 (potentially ranging from 0 to 8 for individual species). Ado-trastuzumab emtansine employs DM1, a semisynthetic cytotoxic payload of the maytansinoid class, which is conjugated via lysine residues of the antibody to an average DAR of 3.5. To understand the effect of DAR on the preclinical properties of ADCs using maytansinoid cytotoxic agents, we prepared a series of conjugates with a cleavable linker (M9346A-sulfo-SPDB-DM4 targeting folate receptor α (FRα)) or an uncleavable linker (J2898A-SMCC-DM1 targeting the epidermal growth factor receptor (EGFR)) with varying DAR and evaluated their biochemical characteristics, in vivo stability, efficacy, and tolerability. For both formats, a series of ADCs with DARs ranging from low (average of ∼2 and range of 0-4) to very high (average of 10 and range of 7-14) were prepared in good yield with high monomer content and low levels of free cytotoxic agent.

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