Introduction： VcMMAE (also known as MC-Val-Cit-PAB-MMAE, mc-vc-PAB-MMAE, or Vedotin) is a specialized drug-linker conjugate identified by CAS:646502-53-6. It serves as a critical component in the synthesis of ADCs, a class of biopharmaceutical drugs designed for targeted cancer therapy. The molecule functions as a payload-linker system that combines a potent cytotoxic agent with a sophisticated delivery mechanism.
Physical and Chemical Properties: Appearance: White to off-white or light yellow solid powder Solubility: Soluble in DMSO and ethanol; insoluble in water Purity: Typically ≥98% Density: 1.196 g/cm³ (predicted)
Mechanism of Action:
The mechanism of VcMMAE is central to the function of ADCs that utilize it:
–Targeted Delivery: The maleimide group allows VcMMAE to be conjugated to tumor-targeting antibodies.
–Selective Release: Upon ADC binding to cancer cell surface antigens and subsequent internalization, the valine-citrulline linker is specifically cleaved by lysosomal enzymes such as cathepsin B.
–Payload Activation: Following linker cleavage, the PAB spacer undergoes spontaneous decomposition, releasing free MMAE into the cytoplasm.
–Antimitotic Activity: MMAE is a potent inhibitor of microtubule polymerization. By disrupting the microtubule network, it arrests cell division and induces apoptosis in malignant cells.
–Bystander Effect: Due to its membrane permeability, MMAE can diffuse out of the target cell and exert cytotoxic activity on neighboring cancer cells, a phenomenon known as the “bystander effect”
Applications:
VcMMAE is exclusively a research and development tool rather than a therapeutic agent itself. Its primary applications include:
–ADC Synthesis: It is widely used as the drug-linker component in the synthesis of antibody-drug conjugates for targeted cancer therapy. Notable ADCs utilizing VcMMAE include brentuximab vedotin (SGN-35), which targets CD30-positive cells.
–Oncology Research: VcMMAE is employed in preclinical evaluation of ADCs, linker stability studies, and targeted cytotoxicity assays.
–Bioconjugation Chemistry: It serves as a reliable platform for optimizing ADC payload delivery, linker cleavage efficiency, and selective cytotoxicity.
–Combination Therapy Studies: Research has demonstrated that MMAE sensitizes colorectal and pancreatic cancer cells to ionizing radiation (IR) in a schedule- and dose-dependent manner.
Biological Activity: VcMMAE-based ADCs have demonstrated remarkable efficacy in preclinical studies: --Potency: They kill antigen-positive cells at low picomolar concentrations. --In Vitro Activity: When conjugated with anti-HER2 antibodies, VcMMAE significantly inhibits viability of HER2-positive cancer cells at concentrations as low as 0.02–0.78 nM. --In Vivo Efficacy: ADCs incorporating VcMMAE have shown significant tumor growth suppression and complete tumor regression in various xenograft models, including lymphomas and Hodgkin's disease
Conclusion: CAS 646502-53-6, or VcMMAE, is an indispensable molecule in the field of targeted cancer therapy. By ingeniously combining a stable antibody-conjugation handle, a cleavable peptide linker, and a highly potent antimitotic agent, it enables the precise delivery of chemotherapy to tumor cells while minimizing systemic toxicity. Its role as a key building block in ADCs continues to drive significant advances in the development of more effective and selective cancer treatments. Product manager: Joy Wu CONTACT/Email address: Joy@coreychem.com
