400647-59-8

Basic information

• Product Name: doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate
• Synonyms: doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate
• CAS NO: 400647-59-8
• Molecular Weight: 762.767
• Mol File: 400647-59-8.mol

Chemical Properties

• CAS DataBase Reference: doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate(400647-59-8)
• EPA Substance Registry System: doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate(400647-59-8)

Safety Data

• Hazardous Substances Data: 400647-59-8(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Doxorubicin-SMCC is used as a non-cleavable ADC linker for the synthesis of antibody-drug conjugates (ADCs). Its application is crucial in the development of targeted cancer therapies, as it enables the covalent attachment of Doxorubicin to monoclonal antibodies, which can then specifically deliver the drug to cancer cells, minimizing damage to healthy cells.
Used in Cancer Research:
In cancer research, Doxorubicin-SMCC is employed as a key component in the creation of ADCs for various types of cancer. Its ability to form stable conjugates with antibodies allows for the precise targeting of cancer cells, potentially improving treatment outcomes and reducing side effects associated with traditional chemotherapy.
Used in Drug Development:
Doxorubicin-SMCC plays a significant role in drug development, particularly in the design and synthesis of novel ADCs. Its unique properties facilitate the development of more effective and selective cancer treatments, contributing to the advancement of personalized medicine and the fight against cancer.

In vitro

ADCs are comprised of an antibody to which is attached an ADC cytotoxin through an ADC linker. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Upstream product

• 64987-85-5 4-(N-maleimidomethyl)cyclohexane-1-carboxylic acid N-succinimidyl ester 
• 25316-40-9 doxorubicin hydrochloride 
• 23214-92-8 doxorubicin 
• 85060-00-0 succinimidyl 4-(N-maleimidomethyl)cyclohexane-1-carboxylate 

Relevant articles and documents

A Flow Cytometric Clonogenic Assay Reveals the Single-Cell Potency of Doxorubicin

Standard cell proliferation assays use bulk media drug concentration to ascertain the potency of chemotherapeutic drugs; however, the relevant quantity is clearly the amount of drug actually taken up by the cell. To address this discrepancy, we have devel

Enhancing cancer targeting and anticancer activity by a stimulus-sensitive multifunctional polymer-drug conjugate

Undesirable physicochemical properties, low tumor targeting, insufficient cell internalization, acquired drug resistance, and severe side effects significantly limit the applications of anticancer drugs. In this study, to improve the tumor targeting and drug efficacy of the poorly water-soluble drug, doxorubicin (DOX), a novel drug delivery platform (PEG-ppTAT-DOX) was developed, which contained a polyethylene glycol (PEG), a matrix metalloproteinase 2 (MMP2)-sensitive peptide linker (pp), a cell penetrating peptide (TAT), and a model drug (doxorubicin). The prepared drug platform possessed several key features, including: (i) the nanoparticle formation via the self-assembly; (ii) prevention of the non-specific interaction via the PEGylation; (iii) tumor targeting via the MMP2-mediated PEG deshielding and exposure of the TAT; (iv) the TAT-mediated cell internalization; (v) the TAT-induced endosomal escape; (vi) the inhibition of P-glycoprotein mediated drug efflux; and (vii) the TAT-medicated nuclear translocation. These cooperative functions ensured the improved tumor targetability, enhanced tumor cell internalization, improved intracellular distribution, and potentiated anticancer activity. Compared to the multi-component nanocarriers, the proposed simple but multifunctional polymer-drug conjugate might have greater potential for tumor-targeted drug delivery and enhanced chemotherapy.

A lysosome-targeted drug delivery system based on sorbitol backbone towards efficient cancer therapy

A straightforward synthetic approach was adopted for the construction of a lysosome-targeted drug delivery system (TDDS) using sorbitol scaffold (Sor) linked to octa-guanidine and tetrapeptide GLPG, a peptide substrate of lysosomal cysteine protease, cathepsin B. The main objective was to efficiently deliver the potential anticancer drug, doxorubicin to the target sites, thereby minimizing dose-limiting toxicity. Three TDDS vectors were synthesized viz., DDS1: Sor-GLPG-Fl, DDS2: Sor-Fl (control) and DDS3: Sor-GLPGC-SMCC-Dox. Dox release from DDS3 in the presence of cathepsin B was studied by kinetics measurement based on the fluorescent property of Dox. The cytotoxicity of DDS1 was assessed and found to be non-toxic. Cellular internalization and colocalization studies of all the 3 systems were carried out by flow cytometry and confocal microscopy utilizing cathepsin B-expressing HeLa cells. DDS1 and DDS3 revealed significant localization within the lysosomes, in contrast to DDS2 (control). The doxorubicin-conjugated carrier, DDS3, demonstrated significant cytotoxic effect when compared to free Dox by MTT assay and also by flow cytometric analysis. The targeted approach with DDS3 is expected to be promising, because it is indicated to be advantageous over free Dox, which possesses dose-limiting toxicity, posing risk of injury to normal tissues. This journal is the Partner Organisations 2014.

Efficient synthesis of doxorubicin melanotransferrin p97 conjugates through SMCC linker

Doxorubicin-succinimidyl 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (SMCC) 3, prepared by treating doxorubicin (1) with SMCC 2, is treated with 2-mercaptoacetic acid to give doxorubicin-SMCC-sulfo-acetic acid 5. Treating with benzotriazol-1-yl-N,N,N′,

The Wittig bioconjugation of maleimide derived, water soluble phosphonium ylides to aldehyde-tagged proteins

Herein we disclose the transformation of maleimides into water-soluble tris(2-carboxyethyl)phosphonium ylides and their subsequent application in the bioconjugation of protein- and peptide-linked aldehydes. The new entry into Wittig bioconjugate chemistry proceeds under mild conditions and relies on highly water soluble reagents, which are likely already part of most biochemists' inventory. This journal is

PSMA TARGETED CONJUGATE COMPOUNDS AND USES THEREOF

PSMA targeted conjugate compounds, pharmaceutical compositions comprising these compounds, methods for treating and detecting cancers in a subject, methods for identifying cancer cells in a sample are described herein.

BIOLOGICAL MATERIALS AND USES THEREOF

The invention provides compounds comprising a therapeutic agent coupled to a carrier molecule, with a minimum coupling ratio of 5: 1; wherein the carrier molecule is (i) an antibody fragment or derivative thereof or (ii) an antibody mimetic or derivative thereof; and wherein the therapeutic agents are coupled onto a lysine amino acid residue; and further wherein the therapeutic agent is not a photosensitising agent. There is also provided uses, methods relating to such compounds, as well as processes for their manufacture.

Intracellular routing in breast cancer cells of streptavidin-conjugated trastuzumab fab fragments linked to biotinylated doxorubicin-functionalized metal chelating polymers

We describe the synthesis of a heterotelechelic metal-chelating polymer (Bi-MCP-Dox), a polyacrylamide with a number average degree of polymerization DPn = 50 (PDI = 1.2), with biotin (Bi) and doxorubicin (Dox) as functional chain ends and diethylenetriaminepentaacetic acid (DTPA) pendant groups as the binding sites for metal ions. We compared its behavior in cell-uptake experiments with a similar polymer (Bi-MCP) without Dox. These MCPs were complexed with trastuzumab Fab (tmFab) fragments covalently linked to streptavidin (SAv) to form tmFab-SAv-Bi-MCP-Dox and tmFab-SAv-Bi-MCP via the strong affinity between Bi and SAv. tmFab targets human epidermal growth factor receptor-2 (HER2), which is overexpressed on certain human breast cancer cells. Surface plasmon resonance (SPR) experiments with the extracellular domain (ECD) of HER2 showed that incorporation of the MCPs in these complexes had no significant effect on the association or dissociation rate with the HER2 ECD and the dissociation constants. The tmFab-complexed MCPs were subsequently labeled with 111In (an Auger electron emitting radionuclide). Auger electrons can cause lethal DNA double strand breaks (DSBs) but only if they are emitted intracellularly and especially, in close proximity to the nucleus. To evaluate the cellular and nuclear uptake of tmFab-SAv-Bi-MCP-Dox, we incubated HER2+ SK-BR-3 human breast cancer cells with the complexes saturated with stable In3+ and visualized their distribution by confocal fluorescence microscopy, monitoring the fluorescence of Dox. In parallel, we carried out cell fractionation studies on tmFab-SAv-Bi-MCP-Dox and on tmFab-SAv-Bi-MCP labeled with 111In. Both radiolabeled complexes showed cell internalization and nuclear localization. We conclude that metal-chelating polymers with this composition appear to encourage internalization, nuclear uptake, and chromatin (DNA) binding of trastuzumab fragments modified with streptavidin in human breast cancer cells expressing HER2. Further study is needed to understand the impact of polymer charge on cellular uptake and distribution to intracellular compartments.

Synthesis of doxorubicin-peptide conjugate with multidrug resistant tumor cell killing activity

Cell penetrating peptide TAT was introduced into doxorubicin structure. Synthesized doxorubicin-TAT conjugate showed different intracellular distribution pattern and cell killing activity from those of free doxorubicin. Unlike free doxorubicin, doxorubici