DOI: 10.5061/dryad.vhhmgqp5m
title: ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1

description: Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s 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) that 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.
description: # ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic
 cancer cells expressing high levels of monocarboxylate transporter MCT1 ##
 Overview This repository contains the raw and processed data supporting
 the results presented in the manuscript eLife-VOR-RA-2023-94488R1. The
 datasets include RNAseq expression values, growth assays,
 immunohistochemistry (IHC) images, in vivo experimental data, and
 supplementary materials related to the study of MCT1-mediated 3BP activity
 in pancreatic ductal adenocarcinoma (PDAC) models. ## Data Organization
 --- ### Figure 1: 3BP sensitivity of PDAC cell lines **Data Files:** *
 Figure 1A source data.xlsx: SYBR Green growth assay numerical and
 normalized data. * Figure 1B source data.xlsx: RNAseq expression values
 from CCLE. * Figure 1B source data for IC50s.pzf: Raw data and IC50
 statistical analysis. * .png files for Figure 1C: Original IHC images
 extracted from Proscia. **Variables and Units:** * Response (% confluence)
 — % * Expression levels (TPM) — Transcripts Per Million (TPM) * IC50 —
 micromolar (µM) --- ### Figure 2: MCT-1 mediates 3BP activity **Data
 Files:** * No source data for Figure 2A (schematic). * Figure 2B summary
 table: Knockout clones. * .png files for Figure 2C-D: IHC images of
 MCT1-KO clones and pooled cells. * Figure 2E, F source data.xlsx: Incucyte
 cell growth raw and normalized data. * Figure 2G source data.xlsx:
 Dose-response Incucyte data. **Variables and Units:** * Clone ID — N/A *
 Confluence — % * Normalized Growth Rate — Relative to baseline (Time 0)
 --- ### Figure 3: Formulations and serum stability of 3BP **Data Files:**
 * Figure 3A source data.tiff: HPLC screenshots. * Figure 3B source
 data.xlsx: Incucyte growth assay in DLD-1. * Figure 3C source data.xlsx:
 Incucyte growth assay in MiaPaCa-2 and MCT1-KO. **Variables and Units:** *
 Peak Area (HPLC) — Arbitrary Units (AU) * % Confluence over time — % ---
 ### Figure 4: MCT1-specific cytotoxicity comparison **Data Files:** *
 Figure 4A-D source data.pzf: Incucyte assays for chemotherapeutics. *
 Figure 4 supplement 1 and 2 source data.xlsx: Extended proliferation
 assays. **Variables and Units:** * Viability — % relative to untreated
 control * Exposure Time — hours (h) --- ### Figure 5: ME3BP-7 inhibits
 tumor growth **Data Files:** * No source data for Figure 5A (schematic). *
 Bioluminescence images for Figure 5B. * Figure 5C source data.xlsx:
 Bioluminescence measurements. * Figure 5D source data.pzf: Tumor weights.
 * Figure 5 supplement 1 source data.xlsx: Mouse body weight tracking.
 **Variables and Units:** * Fold Change in Radiance — Relative Units *
 Tumor Weight — grams (g) * Mouse Body Weight — grams (g) --- ### Figure 6:
 Tumor burden reduction in PDX model **Data Files:** * No source data for
 Figure 6A (schematic). * .png files for Figure 6 B-C (IHC and ultrasound).
 * Figure 6D source data.xlsx: Tumor volumes. * Figure 6E source data.pzf:
 Tumor weights. * .png files for Figure 6F-G: H&E images. * Figure 6H
 source data.pzf: Metastasis counts. * Figure 6 Supplement 1: H&E
 images from various organs. * Figure 6 Supplement 2: TM01098 model data.
 **Variables and Units:** * Tumor Volume — mm³ * Tumor Weight — grams (g) *
 Metastatic Lesion Count — number --- ### Figure 7: Immunohistochemistry
 analysis on PDAC tissue microarray **Data Files:** * .png files for
 Figures 7A-C. * Figure 7 Supplement 1.pzf: TCGA analysis. * Figure 7
 Supplement 2 source data.xlsx: GTEx gene expression data. * .png files for
 Figure 7 Supplement 3: Normal organ IHC. **Variables and Units:** * IHC
 Intensity Score — Scale (0–3) * Expression (GTEx) — TPM --- ###
 Supplementary Movies **Data Files:** * Supplementary Movies 1–3 (.mov
 files): Time-lapse recordings from Incucyte imaging. **Variables and
 Units:** * % Confluence over time --- ## Source Platforms * Expression
 Atlas / CCLE:
 [https://registry.opendata.aws/ccle](https://registry.opendata.aws/ccle) *
 GTEx Portal: [https://gtexportal.org](https://gtexportal.org) * Proscia:
 Digital pathology images * Incucyte System: Live-cell imaging * Waters
 600D HPLC Instrument: Size-exclusion chromatography --- ## Abbreviations |
 Abbreviation | Definition | | :----------- |
 :--------------------------------------- | | ROI | Region of Interest | |
 SLC16A1 | Solute Carrier Family 16 Member 1 (MCT1) | | AU | Arbitrary
 Units | | mm³ | Cubic millimeters | | g | grams | | TPM | Transcripts Per
 Million | | IHC | Immunohistochemistry | | PDX | Patient-Derived Xenograft
 | | SEC | Size-Exclusion Chromatography | --- ## Notes * Data are provided
 in their original format (.xlsx, .pzf, .png, .tiff, .mov). * Refer to the
 manuscript for experimental details and data interpretation. * Timepoints
 such as Day 1 and Day 7 correspond to observation periods after treatment
 or implantation. * Fluorescence data were normalized to baseline
 timepoints and control conditions. * Vessel names primarily refer to
 experimental setups, not measured variables.