ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1
Nearly 30% of pancreatic ductal adenocarcinomas (PDACs) exhibit a marked overexpression of monocarboxylate transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study, we present an alternative approach using 3-bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), which is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule.
Authors
- Evangeline Watson
- Marco Dal Molin (ORCID: https://orcid.org/0000-0003-1581-3576)
- Il Minn (ORCID: https://orcid.org/0000-0002-7822-662X)
- Surojit Sur (ORCID: https://orcid.org/0000-0003-4536-7343)
- Nickolas Papadopoulos (ORCID: https://orcid.org/0000-0001-7135-7451)
- Shun Ishiyama
- Kathleen L. Gabrielson (ORCID: https://orcid.org/0000-0003-3901-4357)
- Kenneth W. Kinzler (ORCID: https://orcid.org/0000-0001-5591-1176)
- Jordina Rincón-Torroella (ORCID: https://orcid.org/0000-0003-4798-8231)
- Nilofer S. Azad (ORCID: https://orcid.org/0000-0002-9613-3988)
- Brian J. Mog (ORCID: https://orcid.org/0000-0001-9988-7147)
- Chetan Bettegowda (ORCID: https://orcid.org/0000-0001-9991-7123)
- Bert Vogelstein (ORCID: https://orcid.org/0000-0003-0766-3854)
- Nicolas Wyhs (ORCID: https://orcid.org/0000-0003-4252-4470)
- Taha Ahmedna (ORCID: https://orcid.org/0000-0003-4786-2292)
- Shibin Zhou (ORCID: https://orcid.org/0000-0003-1941-4425)
- Gyuri Han
Institutions
- Bloomberg (United States) (US)
- Howard Hughes Medical Institute (US)
- Johns Hopkins University (US)
- Johns Hopkins Medicine (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
Publication Details
- Journal
- eLife
- Published
- 2025-05-07
- DOI
- https://doi.org/10.7554/elife.94488.3
- Primary Topic
- Pancreatic and Hepatic Oncology Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Burroughs Wellcome Fund
- Commonwealth Fund
- Lustgarten Foundation
- Ludwig Family Foundation
- National Institutes of Health
- Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University