VcMMAE
[CAS# 646502-53-6]

Identification

• Classification: API >> Antibiotics
• Name: VcMMAE
• Synonyms: Maleimidocaproyl-valine-citrulline-p-aminobenzoyloxycarbonyl-monomethyl auristatin E; Vedotin
• Molecular Formula: C₆₈H₁₀₅N₁₁O₁₅
• Molecular Weight: 1316.63
• CAS Registry Number: 646502-53-6
• EC Number: 809-635-5
• SMILES: CC[C@H](C)[C@@H]([C@@H](CC(=O)N1CCC[C@H]1[C@@H]([C@@H](C)C(=O)N[C@H](C)[C@H](C2=CC=CC=C2)O)OC)OC)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)N(C)C(=O)OCC3=CC=C(C=C3)NC(=O)[C@H](CCCNC(=O)N)NC(=O)[C@H](C(C)C)NC(=O)CCCCCN4C(=O)C=CC4=O

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.556, Calc.^*
• Boiling Point: 1347.6±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 768.8±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Risk Statements: H300+H310+H330-H300-H310-H315-H319-H330-H335
• Safety Statements: P260-P261-P262-P264-P264+P265-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P305+P351+P338-P316-P319-P320-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	1	H300
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	2	H330
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	1	H310
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Reproductive toxicity	Repr.	1B	H360
Acute toxicity	Acute Tox.	1	H330
Specific target organ toxicity - repeated exposure	STOT RE	1	H372
Germ cell mutagenicity	Muta.	2	H341
Specific target organ toxicity - single exposure	STOT SE	1	H370
Germ cell mutagenicity	Muta.	1B	H340

Discovery and Applications

VcMMAE, also known as monomethyl auristatin E, is a synthetic derivative of dolastatin 10, a natural product isolated from the marine mollusk Dolabella auricularia. It was discovered through extensive chemical modifications aimed at enhancing its cytotoxic properties and optimizing its therapeutic potential. VcMMAE was developed as a potent cytotoxic agent capable of selectively targeting cancer cells by inhibiting microtubule assembly and inducing cell cycle arrest and apoptosis.

VcMMAE is widely used in the development of antibody-drug conjugates (ADCs), a class of targeted cancer therapies that combine the specificity of monoclonal antibodies with the cytotoxicity of small-molecule drugs. In ADCs, VcMMAE is conjugated to monoclonal antibodies that selectively bind to tumor-specific antigens expressed on cancer cells. Upon internalization, VcMMAE is released from the antibody and exerts its cytotoxic effects, leading to the selective destruction of cancer cells while sparing healthy tissues. ADCs containing VcMMAE are approved for the treatment of various hematologic malignancies, including relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma. These ADCs have demonstrated efficacy in patients who have failed previous therapies, offering new treatment options for individuals with aggressive or resistant forms of these cancers. VcMMAE-based ADCs are also being investigated for the treatment of solid tumors, including breast cancer, lung cancer, and prostate cancer. Preclinical and clinical studies have shown promising results, with ADCs targeting tumor-associated antigens such as HER2 and Nectin-4 showing antitumor activity in a variety of solid tumor models. VcMMAE is being evaluated in combination with other anticancer agents, including chemotherapy drugs, targeted therapies, and immunotherapies, to enhance treatment efficacy and overcome resistance mechanisms in cancer cells. Combinations of VcMMAE-based ADCs with immune checkpoint inhibitors, for example, aim to leverage the cytotoxic effects of VcMMAE with the immunomodulatory properties of checkpoint blockade, leading to enhanced antitumor immune responses.

References

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