ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1
Data files
Apr 29, 2025 version files 71.45 MB
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README.md
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Source_Data_for_eLife-VOR-RA-2023-94488R1.zip
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Abstract
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.
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
- GTEx Portal: 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.