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

Synonyms

SPDB crosslinker; N-Succinimidyl 4-(2-pyridyldithio)butanoate; Butanoic acid, 4-(2-pyridinyldithio)-, 2,5-dioxo-1-pyrrolidinyl ester

IUPAC Name

Canonical SMILES

C1CC(=O)N(C1=O)OC(=O)CCCSSC2=CC=CC=N2

InChI

InChI=1S/C13H14N2O4S2/c16-11-6-7-12(17)15(11)19-13(18)5-3-9-20-21-10-4-1-2-8-14-10/h1-2,4,8H,3,5-7,9H2

InChIKey

JSHOVKSMJRQOGY-UHFFFAOYSA-N

Solubility

10 mm in DMSO

Appearance

Powder

Quantity

Milligrams-Grams

Shelf Life

Powder: -20°C 12 months; 4°C 6 months<br/>In Solvent: -80°C 6 months; -20°C 3 month

Shipping

Room temperature

Storage

-20°C

Pictograms

Irritant

Signal Word

Warning

Biological Activity

SPDB is a glutathione cleavable ADC linker used for the antibody-drug conjugate (ADCs)[1]

SPDB is a widely used ADC linker designed for precise antibody-drug conjugate (ADC) construction and targeted cancer therapy applications. As an advanced ADC linker, SPDB enables stable conjugation between monoclonal antibodies and potent ADC cytotoxins, ensuring selective delivery of therapeutic payloads to tumor cells. Its chemical structure provides controlled linker stability in circulation and facilitates efficient intracellular release of ADC payloads in the tumor microenvironment. In modern ADC linker design, SPDB supports both cleavable and non-cleavable linker strategies, allowing researchers to optimize pharmacokinetics, therapeutic index, and cytotoxic payload release while maintaining antibody integrity and antigen-binding specificity.

SPDB exhibits broad compatibility with various ADC cytotoxins, including microtubule inhibitors, DNA-targeting agents, and other potent payloads. Its design allows for enzyme-sensitive cleavage in lysosomal compartments, enhancing tumor-specific release of cytotoxic agents while minimizing systemic toxicity. The linker’s chemical stability ensures reliable conjugation efficiency during both small-scale research and large-scale industrial ADC manufacturing. By employing SPDB in ADC linker design, developers can achieve modular bioconjugation strategies that balance stability, payload release, and target specificity, supporting versatile ADC development pipelines across preclinical and clinical stages.

In practical applications, SPDB-based ADC linkers are extensively used in oncology-focused research, bioconjugation studies, and advanced drug delivery systems. Its predictable chemical and enzymatic properties allow for precise design of ADC payload conjugates that maintain antibody function and achieve high tumor accumulation. SPDB supports modern ADC linker architectures that enhance intracellular release of payloads, improve pharmacokinetics, and reduce off-target effects. The linker’s versatility and compatibility with diverse ADC cytotoxins make it a critical component in the design of next-generation antibody-drug conjugates for targeted cancer therapy.

1.Transfer functions of the conjugative integrating element pSAM2 from Streptomyces ambofaciens: characterization of a kil-kor system associated with transfer.

Hagège J;Pernodet JL;Sezonov G;Gerbaud C;Friedmann A;Guérineau M J Bacteriol. 1993 Sep;175(17):5529-38.

pSAM2 is an 11-kb integrating element from Streptomyces ambofaciens. During matings, pSAM2 can be transferred at high frequency, forming pocks, which are zones of growth inhibition of the recipient strain. The nucleotide sequences of the regions involved in pSAM2 transfer, pock formation, and maintenance have been determined. Seven putative open reading frames with the codon usage typical of Streptomyces genes have been identified: traSA (306 amino acids [aa]), orf84 (84 aa), spdA (224 aa), spdB (58 aa), spdC (51 aa), spdD (104 aa), and korSA (259 aa). traSA is essential for pSAM2 intermycelial transfer and pock formation. It could encode a protein with similarities to the major transfer protein, Tra, of pIJ101. TraSA protein contains a possible nucleotide-binding sequence and a transmembrane segment. spdA, spdB, spdC, and spdD influence pock size and transfer efficiency and may be required for intramycelial transfer. A kil-kor system similar to that of pIJ101 is associated with pSAM2 transfer: the korSA (kil-override) gene product could control the expression of the traSA gene, which has lethal effects when unregulated (Kil phenotype). The KorSA protein resembles KorA of pIJ101 and repressor proteins belonging to the GntR family.

2.Design of antibody-maytansinoid conjugates allows for efficient detoxification via liver metabolism.

Sun X;Widdison W;Mayo M;Wilhelm S;Leece B;Chari R;Singh R;Erickson H Bioconjug Chem. 2011 Apr 20;22(4):728-35. doi: 10.1021/bc100498q. Epub 2011 Mar 10.

Antibody-maytansinoid conjugates (AMCs) are targeted chemotherapeutic agents consisting of a potent microtubule-depolymerizing maytansinoid (DM1 or DM4) attached to lysine residues of a monoclonal antibody (mAb) using an uncleavable thioether linker or a stable disulfide linker. Most of the administered dose of an antibody-based therapeutic is slowly catabolized by the liver and other tissues of the reticuloendothelial system. Maytansinoids released from an AMC during this catabolic process could potentially be a source of toxicity. To investigate this, we isolated and identified liver metabolites in mice for three different [(3)H]AMCs with structures similar to those currently undergoing evaluation in the clinic. We then synthesized each metabolite to confirm the identification and assessed their cytotoxic potencies when added extracellularly. We found that the uncleavable mAb-SMCC-[(3)H]DM1 conjugate was degraded to a single major maytansinoid metabolite, lysine-SMCC-[(3)H]DM1, that was nearly 50-fold less cytotoxic than maytansine. The two disulfide-linked conjugates, mAb-SPP-[(3)H]DM1 and mAb-SPDB-[(3)H]DM4, were also found to be catabolized to the analogous lysine-linked maytansinoid metabolites.

3.SPdb--a signal peptide database.

Choo KH;Tan TW;Ranganathan S BMC Bioinformatics. 2005 Oct 13;6:249.

BACKGROUND: ;The signal peptide plays an important role in protein targeting and protein translocation in both prokaryotic and eukaryotic cells. This transient, short peptide sequence functions like a postal address on an envelope by targeting proteins for secretion or for transfer to specific organelles for further processing. Understanding how signal peptides function is crucial in predicting where proteins are translocated. To support this understanding, we present SPdb signal peptide database http://proline.bic.nus.edu.sg/spdb, a repository of experimentally determined and computationally predicted signal peptides.;RESULTS: ;SPdb integrates information from two sources (a) Swiss-Prot protein sequence database which is now part of UniProt and (b) EMBL nucleotide sequence database. The database update is semi-automated with human checking and verification of the data to ensure the correctness of the data stored. The latest release SPdb release 3.2 contains 18,146 entries of which 2,584 entries are experimentally verified signal sequences; the remaining 15,562 entries are either signal sequences that fail to meet our filtering criteria or entries that contain unverified signal sequences.

Catalog	Product Name	CAS
BADC-01467	Lys-Nε-SPDB-DM4	1280215-91-9
BADC-01492	SPDB linker	1284250-78-7
BADC-00018	sulfo-SPDB-DM4	1626359-59-8
BADC-00012	DM4-SPDB	1626359-62-3
BADC-01493	Sulfo-SPDB linker	2095682-79-2
BADC-01407	SPDB-DM1
BADC-01469	Sulfo-SPDB-DGN462

What is SPDB and its application in ADC synthesis?

SPDB is a disulfide-based linker used for site-specific conjugation of payloads to antibodies. Its stable structure allows conjugation to amines, and the disulfide bond enables controlled intracellular release of the payload under reducing conditions, ensuring ADC efficacy.

5/9/2019

Dear BOC Sciences, how does SPDB enable cleavable linkage in ADCs?

The disulfide bond in SPDB is stable in circulation but is reduced by intracellular thiols, such as glutathione, in target cells. This triggers selective release of the payload, enhancing ADC specificity and minimizing off-target effects.

9/8/2022

Dear BOC Sciences, which types of payloads are compatible with SPDB?

SPDB can conjugate amine-containing cytotoxins, peptides, and small molecules. Its spacer design maintains antibody solubility, reduces steric hindrance, and preserves the structural integrity and functionality of both antibody and payload.

28/8/2018

Good afternoon! What are the recommended conjugation conditions for SPDB?

Conjugation is performed in slightly basic aqueous or mixed organic solvents (pH 7.5–8.5) at controlled temperatures to maximize efficiency while preventing hydrolysis and preserving antibody structure.

7/6/2021

Dear BOC Sciences, which analytical documents are available for SPDB to verify its identity and quality?

For SPDB, BOC Sciences provides comprehensive supporting documents including Certificate of Analysis (CoA), NMR spectra, and mass spectrometry data. These documents allow verification of chemical structure, confirm identity, and support analytical reproducibility for research or development applications. All documentation is accessible upon request.

15/8/2021

— Dr. Alexander Schmidt, Senior Chemist (Germany)

SPDB enabled reproducible disulfide linker formation with excellent stability in our ADC constructs.

28/8/2018

— Ms. Grace Wilson, Biochemist (UK)

High solubility and lot consistency of SPDB allowed seamless integration into workflows.

15/8/2021

— Dr. Ethan Parker, Medicinal Chemist (USA)

Using SPDB, we achieved high conjugation efficiency without significant side reactions.

7/6/2021

— Dr. Camille Dubois, Senior Scientist (France)

SPDB performed reliably in multi-step synthesis and supported reproducible results.

5/9/2019

— Mr. Liam Johnson, Research Scientist (Canada)

BOC Sciences provided thorough QC and documentation for SPDB, ensuring smooth ADC development.

— Dr. Peter Johansson, Bioconjugation Specialist (Sweden)

SPDB linker provided by BOC Sciences allowed efficient conjugation and demonstrated excellent stability in our antibody-drug constructs. Highly recommended for complex ADC projects.

9/8/2022