55750-53-3

Basic information

• Product Name: 6-Maleimidocaproic acid
• Synonyms: N-MALEOYL-6-AMINO-CAPROIC ACID;N-EPSILON-MALEIMIDOCAPROIC ACID;N-(5-CARBOXYPENTYL)MALEIMIDE;EMCA;EPSILON-MALEIMIDOCAPROIC ACID;6-MALEIMIDOCAPROIC ACID;6-MALEIMIDOHEXANOIC ACID;6-MALEIMIDOCAPROIC ACID, 98+%
• CAS NO: 55750-53-3
• Molecular Formula: C₁₀H₁₃NO₄
• Molecular Weight: 211.21
• EINECS: 1533716-785-6
• Product Categories: Maleimide Derivatives;Cross Linking Reagents;MTS & Sulfhydryl Active Reagents
• Mol File: 55750-53-3.mol

Chemical Properties

• Melting Point: 86-91 °C
• Boiling Point: 407.3°C at 760 mmHg
• Flash Point: 200.1°C
• Appearance: White to pale yellow/Powder
• Density: 1.285g/cm³
• Vapor Pressure: 8.97E-08mmHg at 25°C
• Refractive Index: 1.536
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Ethyl Acetate (Slightly)
• PKA: 4.74±0.10(Predicted)
• Water Solubility: Soluble in water, methanol, ethanol, dimethyl sulfoxide. Insoluble in ether.
• Sensitive: Moisture Sensitive
• BRN: 1532405
• CAS DataBase Reference: 6-Maleimidocaproic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 6-Maleimidocaproic acid(55750-53-3)
• EPA Substance Registry System: 6-Maleimidocaproic acid(55750-53-3)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-41-37/38
• Safety Statements: 26-36-39
• WGK Germany: 3
• F: 10-21
• Hazardous Substances Data: 55750-53-3(Hazardous Substances Data)

Usage

Uses

Used in Bioconjugation:
6-Maleimidocaproic acid is used as a bifunctional cross-linking reagent for the conjugation of biomolecules with thiol groups. It is particularly useful in the formation of stable amide bonds with primary amine groups, enhancing the stability and functionality of the resulting bioconjugates.
Used in Pharmaceutical Development:
6-Maleimidocaproic acid serves as a probe for introducing maleimide groups into active pharmaceutical ingredients. This allows for the development of new drug candidates with improved properties, such as enhanced solubility, stability, or targeted delivery.
Used in Protein Modification:
In the field of protein chemistry, 6-maleimidocaproic acid is used as a probe for thiol groups in membrane proteins. This enables the modification and functionalization of proteins, which can be crucial for understanding their structure, function, and potential applications in medicine and biotechnology.
Overall, 6-maleimidocaproic acid is a versatile chemical tool with applications in bioconjugation, pharmaceutical development, and protein modification, making it an important compound in the fields of chemistry, biology, and medicine.

InChI:InChI=1/C10H13NO4/c12-8-5-6-9(13)11(8)7-3-1-2-4-10(14)15/h5-6H,1-4,7H2,(H,14,15)

Upstream product

• 57079-14-8 6-(3-carboxyacryloylamino)caproic acid 
• 60-32-2 6-aminohexanoic acid 
• 108-31-6 maleic anhydride 
• 57079-14-8 C₁₀H₁₅NO₅ 
• 108-20-3 di-isopropyl ether 
• 7440-44-0 pyrographite 
• 660-88-8 5-aminopentanoic acid 
• 108-30-5 succinic acid anhydride 

Downstream Products

• 55750-63-5 6-maleimidohexanoic acid N-hydroxylsuccinimide ester 
• 151038-95-8 2-[6-(2,5-Dioxo-1H-pyrrol-1-yl)-1-oxohexyl]hydrazinecarboxylic acid, 1,1-dimethylethyl ester 
• 330641-45-7 C₅₀H₇₃N₇O₁₁S₂ 
• 330641-44-6 C₅₅H₈₁N₇O₁₁S₂ 
• 692739-25-6 pentafluorophenyl 6-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanoate 
• 192212-24-1 tert-butyl 5-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)pentylcarbamate 
• 824955-39-7 C₅₉H₈₉N₉O₁₃S₄ 
• 330641-50-4 C₇₁H₁₁₃N₉O₁₃S₃ 
• 157503-18-9 1-(6-hydroxyhexyl)-1 H-pyrrole- 2,5-dione 
• 82333-93-5 benzyl N-(4-aminophenethyl)-N-methyl-L-valinate dihydrochioride 
• 558483-53-7 C₂₀H₃₁NO₆ 
• 558483-51-5 C₃₁H₄₄N₂O₁₀ 
• 1033039-28-9 C₅₅H₈₇N₅O₁₃ 
• 1108206-63-8 C₆₁H₅₃N₃O₁₂ 

Relevant articles and documents

Photopolymerization of maleimide perfluoropolyalkylethers without a photoinitiator

Perfluoropolyalkylethers derived from hexafluoropropylene oxide were functionalized with maleimide groups. Irradiated by UV-light, the new maleimide macromonomers demonstrated very fast polymerization kinetics with a curing time as fast as 8 s. The effect on photopolymerization of different features such as the molecular weight of the fluorinated chain and the chain length of the hydrogenated spacer were studied, as well as the influence of the type of photoinitiator and the presence of air. Thermal and surface properties of the UV-cured polymers were examined and were typical to fluoropolymers in view of water–oil repellent coatings.

Preparation of a New PEGylation Reagent for Sulfhydryl-containing Polypeptide

N-maleimido-6-amino-caproyl ester of PEG was preparated in the presence of DCC etc., as a new sulfhydryl-PEGylation reagent substituted for mal-sac-PEG.

Multifunctional Tumor-Targeting Cathepsin B-Sensitive Gemcitabine Prodrug Covalently Targets Albumin in Situ and Improves Cancer Therapy

We report a new type of amide bond-bearing cathepsin B-sensitive gemcitabine (GEM) prodrugs, capable of in situ covalently targeting circulating albumin and then making a hitchhike to the tumor. Specially, less plasma-enzyme deactivation, long plasma half-life, independence on nucleoside transporters, outstanding tumor targeting, and site-specific drug release are achieved, and as such these multifunctional advantages contribute to the dramatically increased in vivo antitumor efficacy.

Novel fatty acid chain modified GLP-1 derivatives with prolonged in vivo glucose-lowering ability and balanced glucoregulatory activity

Glucagon-like peptide-1 is a potent hypoglycemic hormone with beneficial properties for the treatment of diabetes. However, its half-life is short because the rapid metabolic degradation. This study aims to prolong the half-life of glucagon-like peptide-1 through conjugation with the fatty acid side chain which helps the conjugates to interact with the albumin. Firstly, we chose two optimized polypeptide chains which have tremendous hypoglycemic effect named Cys17-Gly8-GLP-1(7-36)-NH2 and Cys37-Gly8-GLP-1(7-37)-NH2, and various fatty acid chains were modified. All conjugates preserved relatively strong GLP-1R activation and I-6 behaved best in glucose-lowering ability. The prolonged antidiabetic effects of I-6 were further confirmed by hypoglycemic efficacy test in vivo. Meanwhile, once daily injection of I-6 to diabetic mice achieved long-term beneficial effects on glucose tolerance, body weight and blood chemistry. It is concluded that I-6 is a promising agent for further investigation of its potential to treat obese patients with diabetes.

Cytosine arabinoside prodrug designed to bind plasma serum albumin for drug delivery

Rational design of anticancer prodrugs for efficient albumin binding can show distinct advantages in drug delivery in terms of high drug availability, long systemic circulation, potential targeting effect, and enhanced chemotherapy effect. In the present study, we reported a cytosine arabinoside (Ara-C) prodrug which could well formulate in solution and instantly transform into long-circulating nanocomplexes by hitchhiking blood-circulating albumin after i.v. administration. Specifically, Ara-C was conjugated with an albumin-binding maleimide derivative, the resulting Ara-C maleimide caproic acid conjugate (AM) was well formulated in aqueous solution, conferring high albumin-binding ability in vitro albumin-binding studies. Moreover, in vivo fluorescence images of sulfo-cyanine5 maleimide indirectly demonstrated that AM showed better accumulation in tumors, exhibiting superior tumor targeting ability and antitumor activity compared to Ara-C. Such a uniquely developed strategy, integrating high albumin-binding capability, has great potential to be applied in clinical cancer therapy.

Development of bifunctional anti-PD-L1 antibody MMAE conjugate with cytotoxicity and immunostimulation

In recent years, tumor immunotherapy, especially the combination of PD1/PD-L1 inhibitors and chemotherapy, has developed rapidly. However, the systemic side effects induced by chemotherapy remain a crucial problem that needs to be addressed. Antibody drug conjugates (ADCs) are exceptional target-specific prodrugs that greatly improve the therapeutic window of chemotherapy drugs. Therefore, designing PD-L1-targeting ADCs is an interesting research project. In this study, we confirmed for the first time that the commercial anti-PD-L1 antibody Atezolizumab has better endocytosis efficiencies than Avelumab, and was more suitable for ADC design. Then, the most popular cytotoxic payload MMAE was conjugated to Atezolizumab via a classical dipeptide (valine-alanine) linker to generate a bifunctional PD-L1 ADC (ADC 3). An in vitro cytotoxicity test indicated the potent tumor cell inhibitory activity of ADC 3, with EC50 values of 9.75 nM to 11.94 nM. In addition, a co-culture of PBMCs in vitro proved that ADC 3 retained the immune activation effect of the Atezolizumab antibody. Moreover, ADC 3 exhibited a higher tumor inhibition rate and tumor regression rate in humanized immune system mice. To the best of our knowledge, this is the most active PD-L1-ADC reported thus far, which may promote the development of immunotherapy and novel ADCs.

Linker, Antibody-Drug Conjugate Including Same and Use Thereof

Provided are a linker represented by Formula I or I′, an antibody-drug conjugate containing the same, and use of thereof, a pharmaceutical composition comprising the antibody-drug conjugate, and use of the antibody-drug conjugate for treating and/or preventing a disease.

Synthesis, characterization, and targeted chemotherapy of SCT200-linker-monomethyl auristatin E conjugates

Antibody-drug conjugates (ADCs) are currently among the most successful and important strategies for treating patients with solid tumors. ADCs are composed of a monoclonal antibody and warhead, which are conjugated via a linker. Currently, monomethyl auristatin E (MMAE) is the most widely applied warhead in the development of ADCs. However, MMAE-based ADCs are generally constructed using the MC-VC-PABC linker, and this design has limited structural diversity and some disadvantages. Accordingly, in this study, we generated three types of novel linker-MMAE (with alterations in the spacer, catabolizing area, and self-immolative compared with MC-VC-PABC-MMAE) in ADCs, termed SCT200-linker-MMAE conjugates, and then evaluated the linker-drug plasma stability and the rate of drug release by cathepsin B. The binding ability, internalization rates, and efficacy of all SCT200-linker-MMAE ADCs were systematically studied, and the expression of apoptosis-associated proteins and the therapeutic efficacies of SCT200-M-2, -C-2, and -C-4 were evaluated. The results showed that the activities of some of these ADCs were increased for epidermal growth factor receptor-positive tumors. Moreover, the novel linkers designed in this study can be linked with other antibodies to treat other types of cancer. Overall, these findings provide important insights into the application of SCT200-based linkers in ADCs.

A designed cyclic peptide based on Trastuzumab used to construct peptide-drug conjugates for its HER2-targeting ability

Human epidermal growth factor receptor 2 (HER2) has been recognized as an important therapeutic target for its overexpression in many cancers. Trastuzumab is a monoclonal antibody targeting HER2, which has been approved by FDA to treat HER2-positive cancer. In this research, cyclic peptide Cyclo-GCGPep1 was designed based on the binding mode between antibody and HER2 protein in silico, which has been confirmed possessing good affinity with HER2. Cyclo-GCGPep1 was also used to construct peptide-drug conjugates with Camptothecin. Biological evaluations demonstrated that Conjugate 1 has a good antiproliferative activity on SK-BR-3 and NCI-N87 cells. Conjugate 1 retained the pro-apoptotic and Topo I inhibitory ability of Camptothecin. Meanwhile, it has good targeting ability towards HER2-positive cells with the help of Cyclo-GCGPep1. It also has better permeability in the tumor spheroid model than Camptothecin. In summary, the design of cyclic peptide derived from antibody is of significance for the discovery of targeting peptides and Conjugate 1 is expected as a good therapeutic agent for HER2-positive cancers.

Antibody-drug conjugate using ionized CYS-linker-mmae as the potent payload shows optimal therapeutic safety

Monomethyl auristatin E (MMAE) is the most popular and widely used cytotoxin in the development of antibody-drug conjugates (ADCs). However, current MMAE-based ADCs are all constructed using cleavable linkers, and this design concept still has insurmountable drawbacks. Their potential instabilities and lipophilic MMAE-induced “bystander effect” inevitably increase the toxicity to normal tissues. Herein, we overturn previous negative views of MMAE-based ADCs with non-cleavable linkers and propose using ionized L-Cysteine (Cys)-linker-MMAE as a novel payload, which can ingeniously enrich and enter tumor cells through receptor-mediated endocytosis of antibodies while its lower permeability helps to avoid further off-target toxicity. We demonstrate that Cys-linker-MMAE maintains high potency similar to free MMAE at the tubulin molecular level and can also be efficiently released in target cells. As a result, the preferred ADC (mil40-15) not only exhibits ideal plasma stability and maintains potent cytotoxicity as MMAE (IC50: 10?11 M), but also shows improved safety with lower bystander toxicity (IC50: 10?9 M), its maximum tolerated dose approaching the level of the naked antibody (160 mg/kg). This study indicated that Cys-linker-MMAE has the potential as a potent payload for ADCs, which is expected to provide novel strategies for the development of MMAE-based ADCs.