Prodrug-Methotrexate Peptide/Alanine

Creative Biolabs offers high-quality methotrexate peptide/alanine as a prodrug for antibody-directed enzyme prodrug therapy (ADEPT) development service to every client. Our best prodrug and conjugation strategy will facilitate your project.

Methotrexate Peptide/Alanine

Methotrexate (MTX), which was made in 1947 and formerly referred to as amethopterin, is a medical chemotherapy agent and immune system suppressant. With less toxic than early treatment, methotrexate is used to treat autoimmune diseases (such as psoriasis, rheumatoid arthritis, and Crohn's disease), ectopic pregnancy, medical abortions and for some types of cancers including breast cancer, leukemia, lung cancer, lymphoma, and osteosarcoma. Thus, it is treated as the most effective and safe medicines needed in the health system. Particularly, it is listed as one of the Essential Medicines in the World Health Organization. Methotrexate peptide/alanine (derivatives in which amino acids are linked covalently to the a-carboxyl group of MTX) is the prodrug of methotrexate, the prodrug form of the parent antifolate. These compounds are much less toxic to cells than MTX, presumably because of their inability to be internalized by folate transport systems.

MOA of Methotrexate Peptide/Alanine

The prodrug methotrexate peptide/alanine can be activated by carboxypeptidase A hydrolysis, yielding the parent drug methotrexate. Methotrexate can competitively and irreversibly inhibit dihydrofolate reductase, an enzyme that plays a critical role in tetrahydrofolate synthesis. Dihydrofolate reductase catalyzes the conversion of dihydrofolate into the active tetrahydrofolate. Folic acid is essential for the de novo synthesis of the nucleoside, thymidine, required for DNA synthesis. In addition, some other enzymes that are indirectly affected by methotrexate including 5,10-methylenetetrahydrofolate reductase and methylenetetrahydrofolate dehydrogenase. Therefore, methotrexate has the ability to inhibit the synthesis of DNA, RNA, thymidylates, and proteins.

Overview of methotrexate mechanisms of action. Fig.1 Overview of methotrexate mechanisms of action. (Kaltsonoudis, 2012)

Methotrexate Peptide/Alanine-based ADEPT

Over the past decades, ADEPT has been treated as an attractive therapeutic strategy for cancer treatment. The antibody component provides the agent with exquisite specificity for targeting both primary tumors and metastases. The enzyme element can be localized and used to activate a prodrug. Methotrexate peptide/alanine as a prodrug in ADEPT has been demonstrated therapeutic potential in various forms. Evidence demonstrated that the synthesis of methotrexate (MTX) prodrugs was successfully and confirmed no cytotoxicity, but hydrolysis with tumor-targeted scFv/hCPA fusion protein gave 1,000-fold higher cytotoxicity than MTX-a-Phe only. In addition, cell cycle assays indicated that tumor cells were arrested in the S phase after ADEPT treatment, and tumors were inhibited significantly in scFv/hCPA and MTX-a-Phe treated mice.

Mechanism of ADEPT action. Fig.2 Mechanism of ADEPT action. (Begent, 2010)

Creative Biolabs offers high-quality prodrug-methotrexate peptide/alanine, advanced organic synthesis platform and experienced scientist team to help you develop methotrexate peptide/alanine-based ADEPT in a timely and cost-effective manner. We also provide other services regarding ADEPT development. Please feel free to contact us for more information and a detailed quote.


  1. Kaltsonoudis, E.; et al. Current and future role of methotrexate in the therapeutic armamentarium for rheumatoid arthritis. International Journal of Clinical Rheumatology. 2012, 7(2), 179.
  2. Begent, R.; et al. Antibody-dependent enzyme prodrug therapy (ADEPT). In Antibody Engineering. 2010, (pp. 431-451). Springer, Berlin, Heidelberg.

Related Sections

Antibody-directed Enzyme Prodrug Therapy (ADEPT): Antibody-enzyme Conjugates for Cancer Therapy: Services:
Online Inquiry
*E-mail Address:
*Products or Services Interested:
Project Description:
*Verification Code:
Please input "biolabs"(case insensitive) as verification code.

Welcome! For price inquiries, please feel free to contact us through the form on the left side. We will get back to you as soon as possible.

Contact us
 45-1 Ramsey Road, Shirley, NY 11967, USA
 Tel: 1-631-357-2254
 Fax: 1-631-207-8356
Heidenkampsweg 58, 20097 Hamburg, Germany
 Tel: 44-207-097-1828