Name: sulfo-SPDB-DM4
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

Maytansinoid DM4- succinimidyl 4-(N-maleimidomethyl)cyclohexane-3-sulfo-carboxylate

IUPAC Name

4-[[5-[[(2S)-1-[[(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]oxy]-1-oxopropan-2-yl]-methylamino]-2-methyl-5-oxopentan-2-yl]disulfanyl]-1-(2,5-dioxopyrrolidin-1-yl)oxy-1-oxobutane-2-sulfonic acid

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

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

InChIKey

ACJLJPQSHWOFQD-SKUWBIDSSA-N

Density

1.44±0.1 g/cm3

Solubility

DMSO

Appearance

Soild powder

Shipping

Room temperature, or blue ice upon request.

Storage

Store in a cool and dry place (or refer to the Certificate of Analysis).

Sulfo-SPDB-DM4 is a high-performance ADC Cytotoxin with Linker designed for targeted cancer therapy and advanced antibody-drug conjugate (ADC) development. This potent ADC Cytotoxin combines the cytotoxic potency of DM4 with a stable sulfonated SPDB linker, enabling efficient delivery of the payload to tumor cells while minimizing systemic toxicity. The ADC Linker plays a critical role in maintaining stability in circulation and ensuring controlled release of the ADC payload upon internalization by target cells.

The mechanism of sulfo-SPDB-DM4 involves selective binding of the antibody component to tumor-associated antigens, followed by internalization and proteolytic cleavage of the ADC linker, releasing the DM4 payload intracellularly. This process facilitates microtubule disruption, leading to apoptosis of malignant cells. As an optimized ADC Cytotoxin, sulfo-SPDB-DM4 is highly relevant for researchers and developers working on targeted therapeutics, bioconjugation techniques, and ADC pipeline expansion. Its design ensures both efficacy and safety, critical parameters for preclinical and clinical ADC applications.

Sulfo-SPDB-DM4 also supports versatile ADC bioconjugation strategies, allowing efficient coupling with various monoclonal antibodies. The water-soluble sulfonated linker enhances conjugation efficiency and solubility, addressing common challenges in ADC formulation and development. This feature makes it a preferred choice for pharmaceutical scientists exploring novel ADC payload-linker combinations, tumor-targeting modalities, and next-generation oncology therapeutics. Incorporating this ADC Cytotoxin with Linker into research workflows can accelerate development timelines and improve the therapeutic index of antibody-based drugs.

Applications of sulfo-SPDB-DM4 include preclinical testing of antibody-drug conjugates, ADC optimization studies, and investigation of targeted cytotoxic delivery mechanisms. Its reliable performance in ADC payload release and linker stability evaluation makes it an essential tool for cancer research, bioconjugation chemistry, and translational oncology programs.

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.

Catalog	Product Name	CAS
BADC-00017	DM4-SMCC	1228105-52-9
BADC-01467	Lys-Nε-SPDB-DM4	1280215-91-9
BADC-00600	Sulfo-PDBA-DM4	1461704-01-7
BADC-00012	DM4-SPDB	1626359-62-3
BADC-00011	DM4-SPDP	2245698-48-8
BADC-00021	DM4-SMe	796073-68-2
BADC-00347	DM4	796073-69-3
BADC-00087	Maytansinoid DM4	799840-96-3
BADC-01365	S-Me-DM4	890654-03-2
BADC-00704	DBA-DM4	905449-84-5

What is sulfo-SPDB-DM4?

sulfo-SPDB-DM4 is an antibody-drug conjugate (ADC) linker-payload. It is comprised of a cleavable linker (sulfo-SPDB) and a potent tubulin-targeting payload (DM4). This combination is used for the site-specific conjugation of antibodies to create ADCs for targeted drug delivery in cancer therapy.

12/12/2018

We would like to know how sulfo-SPDB-DM4 is used in ADC development.

sulfo-SPDB-DM4 is used as a crucial component in the synthesis of ADCs. The sulfo-SPDB linker, a non-cleavable maleimide-based linker, ensures stable attachment to the antibody, while the DM4 payload provides the cytotoxic activity. Its use allows for the creation of ADCs with high stability and a consistent drug-to-antibody ratio (DAR).

9/3/2019

Good morning! Could you please explain the key advantages of using sulfo-SPDB-DM4?

The primary advantage of sulfo-SPDB-DM4 lies in its stability and targeted delivery. The sulfo-SPDB linker is designed to be highly stable in circulation, minimizing premature payload release. This feature reduces systemic toxicity. The DM4 payload, a highly potent tubulin inhibitor, ensures effective cell killing upon reaching the target site.

28/11/2020

Could you please explain what the mechanism of action of the DM4 payload is?

The DM4 payload is a maytansinoid, a class of potent antimitotic agents. Its mechanism of action involves the inhibition of tubulin polymerization, which disrupts the microtubule network within cancer cells. This disruption leads to cell cycle arrest at the G2/M phase and subsequent apoptosis, or programmed cell death.

18/9/2020

Good afternoon! Could you explain why the sulfo-SPDB linker is important?

The sulfo-SPDB linker is a key part of the sulfo-SPDB-DM4 construct. It provides a covalent and stable connection between the antibody and the DM4 payload, a critical feature for maintaining the integrity of the ADC in the bloodstream. This linker also features a sulfo group, enhancing its water solubility and facilitating its use in aqueous conjugation reactions.

25/9/2017

— Dr. Laura Bennett, Senior Scientist (USA)

The high purity of sulfo-SPDB-DM4 enabled accurate ADC conjugation and reliable assay results in our lab.

28/11/2020

— Dr. Michael Carter, ADC Chemist (UK)

We appreciated the rapid shipment of sulfo-SPDB-DM4, which helped us meet a tight project deadline.

25/9/2017

— Dr. Stefan Müller, Medicinal Chemist (Germany)

Technical advice provided by BOC Sciences was invaluable for optimizing sulfo-SPDB-DM4 handling.

18/9/2020

— Dr. Emily White, Biochemist (Canada)

Consistency across batches of sulfo-SPDB-DM4 reduced variability and improved experiment reproducibility.