Name: SMCC
Brand: BOC Sciences
Price: 298 USD
Availability: MadeToOrder

Synonyms

4-(N-Maleimidomethyl)cyclohexane-1-carboxylic Acid N-Hydroxysuccinimide Ester; NSC 344483; N-Succinimidyl 4-(Maleimidomethyl)cyclohexane-1-carboxylate; Cyclohexanecarboxylic acid, 4-[(2,5-dihydro-2,5-dioxo-1H-pyrrol-1-yl)methyl]-, 2,5-dioxo-1-pyrrolidinyl ester; 1H-Pyrrole-2,5-dione, 1-[[4-[[(2,5-dioxo-1-pyrrolidinyl)oxy]carbonyl]cyclohexyl]methyl]-; 2,5-Dioxopyrrolidin-1-yl 4-((2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)methyl)cyclohexanecarboxylate; 4-(2,5-Dioxo-2,5-dihydro-pyrrol-1-ylmethyl)-cyclohexanecarboxylic acid 2,5-dioxo-pyrrolidin-1-yl ester; N-Hydroxysuccinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate; N-Succinimidyl 4-(maleimidomethyl)cyclohexanecarboxylate; Succinimidyl 4-(maleimidomethyl)cyclohexane-1-carboxylate; Succinimidyl 4-(N-maleimidomethyl)cyclohexanecarboxylate; Succinimidyl 4-[maleimidomethyl]cyclohexan-1-carboxylate

IUPAC Name

(2,5-dioxopyrrolidin-1-yl) 4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexane-1-carboxylate

Canonical SMILES

C1CC(CCC1CN2C(=O)C=CC2=O)C(=O)ON3C(=O)CCC3=O

InChI

InChI=1S/C16H18N2O6/c19-12-5-6-13(20)17(12)9-10-1-3-11(4-2-10)16(23)24-18-14(21)7-8-15(18)22/h5-6,10-11H,1-4,7-9H2

InChIKey

JJAHTWIKCUJRDK-UHFFFAOYSA-N

Density

1.42±0.1 g/cm<sup>3</sup>(Predicted)

Solubility

Soluble in Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

Melting Point

172-174°C

Appearance

White to off-white solid

Shipping

Room temperature

Storage

Store at -20°C

Pictograms

Irritant

Signal Word

Warning

Boiling Point

501.7±42.0°C at 760 mmHg

SMCC is a widely utilized ADC linker in the design and development of antibody-drug conjugates. As a heterobifunctional linker, SMCC contains an N-hydroxysuccinimide (NHS) ester and a maleimide functional group, enabling site-specific conjugation between lysine residues on antibodies and thiol-containing ADC cytotoxins. Its cyclohexyl spacer provides structural rigidity and chemical stability, which is essential for maintaining the integrity of the ADC during circulation and ensuring controlled delivery of the payload to target tumor cells.

In ADC linker design, SMCC facilitates stable covalent attachment while minimizing linker hydrolysis and premature payload release. The maleimide group reacts efficiently with reduced cysteine residues on the antibody, providing a reproducible method for achieving defined drug-to-antibody ratios (DAR). This property supports the development of ADCs with predictable pharmacokinetic and pharmacodynamic profiles, critical for oncology therapeutics and other targeted bioconjugation applications.

The chemical stability of SMCC under physiological conditions ensures that ADC payloads remain conjugated until reaching the tumor microenvironment, where controlled release mechanisms can act on the cytotoxin. Its heterobifunctional structure allows compatibility with a wide range of cytotoxic payloads, including microtubule inhibitors, DNA-damaging agents, and other potent ADC payloads, making it a versatile tool in ADC research and development.

SMCC is commonly applied in bioconjugation strategies requiring precise antibody-to-payload attachment and robust linker stability. Its integration in ADC design improves solubility, reduces aggregation, and maintains antibody functionality, making it a standard choice for constructing high-performance antibody-drug conjugates for targeted cancer therapy.

1.A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies.

Deckert J1, Park PU, Chicklas S, Yi Y, Li M, Lai KC, Mayo MF, Carrigan CN, Erickson HK, Pinkas J, Lutz RJ, Chittenden T, Lambert JM. Blood. 2013 Nov 14;122(20):3500-10. doi: 10.1182/blood-2013-05-505685. Epub 2013 Sep 3.

CD37 has gathered renewed interest as a therapeutic target in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, CD37-directed antibody-drug conjugates (ADCs) have not been explored. Here, we identified a novel anti-CD37 antibody, K7153A, with potent in vitro activity against B-cell lines through multiple mechanisms including apoptosis induction, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity. The antibody was conjugated to the maytansinoid, DM1, a potent antimicrotubule agent, via the thioether linker, N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), and the resulting ADC, IMGN529, retained the intrinsic antibody activities and showed enhanced cytotoxic activity from targeted payload delivery. In lymphoma cell lines, IMGN529 induced G2/M cell cycle arrest after internalization and lysosomal processing to lysine-N(ε)-SMCC-DM1 as the sole intracellular maytansinoid metabolite.

2.Trastuzumab emtansine: first global approval.

Ballantyne A1, Dhillon S. Drugs. 2013 May;73(7):755-65. doi: 10.1007/s40265-013-0050-2.

Genentech and ImmunoGen are collaborating on the development of trastuzumab emtansine, a HER2 antibody-drug conjugate that comprises Genentech's trastuzumab antibody linked to ImmunoGen's anti-mitotic agent, mertansine (a maytansine derivative; also known as DM1). The conjugate combines two strategies: the anti-HER2 activity of trastuzumab, and the targeted intracellular delivery of mertansine, a tubulin polymerisation inhibitor which interferes with mitosis and promotes apoptosis. The linker in trastuzumab emtansine is a non-reducible thioether linker, N-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC, designated MCC after conjugation). Trastuzumab emtansine (Kadcyla™) has been launched in the USA as second-line monotherapy for HER2-positive metastatic breast cancer, and has been filed for approval in the EU and Japan in this indication. Trastuzumab emtansine is in phase III development as first-line combination therapy or monotherapy for metastatic HER2-positive breast cancer, and as third-line monotherapy for metastatic HER2-positive breast cancer.

3.Synthesis of a stable and specific surface plasmon resonance biosensor surface employing covalently immobilized peptide nucleic acids.

Burgener M1, Sänger M, Candrian U. Bioconjug Chem. 2000 Nov-Dec;11(6):749-54.

Biosensors allow the real-time and label-free observation of biochemical reactions between various ligands including antigen-antibody reactions and nucleic acids hybridizations. In our studies, we used a surface plasmon resonance biosensor to elucidate the hybridization characteristics of a peptide nucleic acid (PNA) ligand immobilized on sensor surfaces either through covalent or streptavidin-biotin coupling. A biotin-labeled PNA was employed in the latter approach whereas the covalent immobilization included the following steps: A maleimide group was attached to the N-terminal of the PNA using N-succinimidyl 4-(N-maleimidomethyl)-cyclohexane-1-carboxylate (SMCC). To generate free thiol groups for coupling, a carboxylated dextran matrix of the sensor surface was activated with N-hydroxysuccinimide (NHS) and N-ethyl-N'-(dimethylaminopropyl)-carbodiimide (EDC) and thiolated by addition of cystamine dihydrochloride followed by reduction with 1, 4-dithioerythrite (DTE).

4.Dual potency anti-HER2/neu and anti-EGFR anthracycline immunoconjugates in chemotherapeutic-resistant mammary carcinoma combined with cyclosporin A and verapamil P-glycoprotein inhibition.

Coyne CP1, Ross MK, Bailey JG. J Drug Target. 2009 Jul;17(6):474-89. doi: 10.1080/10611860903012802.

Immunoconjugates of epirubicin were synthesized with monoclonal antibodies against the epidermal growth factor receptors, HER2/neu and EGFR, by creating a sulfhydryl-reactive epirubicin intermediate applying heterobifunctional succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), which was introduced at alpha-monoamide groups of the epirubicin carbohydrate moiety. In parallel, N-succinimidyl-S-acetylthioacetate (SATA) was used to incorporate a sulfhydryl group into immunoglobulin at the terminal amine position of -lysine amino acid residues. Eprirubicin-SMCC-SATA-IgG immunoconjugates were produced by reacting epirubicin-SMCC and SATA-IgG at appropriate molar ratios. Epirubicin-(anti-HER2/neu) and epirubicin-(anti-EGFR) had greater potency against chemotherapeutic-resistant SKBr-3 mammary carcinoma than did epirubicin at epirubicin-equivalent concentrations. Epirubicin-(anti-HER2/neu) was more potent than epirubicin-(anti-EGFR), and a synergistic level of antineoplastic activity was detected with an epirubicin immunoconjugate 50/50 combination.

HPLC

HNMR

Catalog	Product Name	CAS
BADC-00009	DM1-SMCC	1228105-51-8
BADC-00017	DM4-SMCC	1228105-52-9
BADC-00574	Lys-SMCC-DM1	1281816-04-3
BADC-00856	MMAE-SMCC	2021179-11-1
BADC-01487	MPr-SMCC	2259873-94-2
BADC-01122	Doxorubicin-SMCC	400647-59-8
BADC-01192	Sulfo-SMCC sodium	92921-24-9

What is SMCC?

SMCC (succinimidyl 4-(maleimidomethyl)cyclohexane-1-carboxylate) is a heterobifunctional crosslinker widely used in ADC development. It contains NHS ester and maleimide groups enabling conjugation between amine- and thiol-containing biomolecules, supporting stable linker attachment.

17/12/2022

We would like to know the recommended storage conditions for SMCC.

SMCC should be stored at low temperatures, protected from moisture and light. Proper storage maintains reactivity of NHS ester and maleimide functionalities, ensuring consistent conjugation efficiency and experimental reproducibility.

12/2/2018

We are interested in knowing what specifications are provided for SMCC.

Specifications include molecular weight, functional group ratio, solubility properties, and linker structure. These details assist researchers in planning conjugation reactions while avoiding disclosure of purity data.

8/2/2019

Are support documents provided for SMCC?

Yes, SMCC comes with detailed chemical structure information, handling guidelines, and suggested conjugation protocols. These documents help researchers optimize ADC synthesis and experimental workflows.

29/10/2016

Good afternoon! Could you explain how SMCC quality is verified?

SMCC quality is verified through analytical methods such as NMR, LC-MS, and HPLC to confirm molecular structure and functional group integrity. This ensures reliability for ADC linker applications in research.

22/8/2021

— Dr. Peter Adams, Medicinal Chemist (UK)

SMCC provided by BOC Sciences consistently produced high coupling efficiency in our antibody conjugation experiments.

8/2/2019

— Ms. Laura Bennett, Biochemist (USA)

The SMCC batch quality was outstanding, with minimal side reactions observed during conjugation.

22/8/2021

— Dr. François Martin, Senior Researcher (France)

SMCC was supplied with excellent solubility and stability, making our ADC synthesis workflow much more predictable.

29/10/2016

— Dr. Katherine Lewis, Bioconjugation Scientist (Canada)

High-purity SMCC enabled efficient cross-linking, saving significant time in our ADC production.