---
title: "CYP1A2 metabolizes organophosphorus pesticides and nerve agent surrogates"
id: "biorxiv-21-human-cyp1a2-metabolism-of-organophosphorus-pesticides-and-nerve-agent"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-21-human-cyp1a2-metabolism-of-organophosphorus-pesticides-and-nerve-agent"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1?rss=1"
published_at: "2026-10-25T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# CYP1A2 metabolizes organophosphorus pesticides and nerve agent surrogates
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-21-human-cyp1a2-metabolism-of-organophosphorus-pesticides-and-nerve-agent
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1?rss=1)
- **Published At:** 2026-10-25T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study assessed human **CYP1A2** capacity to metabolize and be inhibited by organophosphorus (OP) pesticides and nerve agent surrogates using LC-MS/MS and a pFluor50 inhibition assay. - Investigators reported that **CYP1A2** comprises roughly 13–15% of hepatic CYP450 content and handles about 10% of drug metabolism; this enzyme preferentially metabolized thion (P=S) forms over oxon (P=O) forms in the tested panel. - Several OP compounds inhibited CYP1A2 activity in a time- and dose-dependent fashion when measured by the pFluor50 assay, with correlation analysis linking inhibition at 10 μM (30-minute preincubation) to residual OP at 2 hours (R = -0.71, P<0.001). - Molecular docking using the CYP1A2 crystal structure (PDB ID: 2HI4) was performed to explore binding interactions; the source reported docking but did not provide detailed binding poses or energy values in the abstract. - The authors proposed **CYP1A2** as a potential bioscavenger for OP compound metabolism and recommended integrating experimental and in silico data to build AI/ML models for predicting CYP1A2-mediated metabolism of existing and emerging OP agents. - Funding was declared from the Defense Threat Reduction Agency (HDTRA11910020). The paper is a preprint and has not undergone peer review; the source did not report clinical dosing, subject demographics, or extended methodological specifics in the abstract.
## Clinical Analysis & Structured Key Points
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Pratik Shriwas 1 Sastra University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Pratik%2BShriwas%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Shriwas%20P&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3APratik%2BShriwas%2B) * [ORCID record for Pratik Shriwas](http://orcid.org/0000-0003-2582-2118 "Open in new tab") Matthew Politeski, 2 Ohio State University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Matthew%2BPoliteski%2C%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Politeski%2BM&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AMatthew%2BPoliteski%252C%2B) Brian Scarpitti 2 Ohio State University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Brian%2BScarpitti%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Scarpitti%20B&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ABrian%2BScarpitti%2B) Sean Ekins 3 Collaborations Pharmaceuticals, Inc.; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sean%2BEkins%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Ekins%20S&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASean%2BEkins%2B) * [ORCID record for Sean Ekins](http://orcid.org/0000-0002-5691-5790 "Open in new tab") Thomas R Lane 4 Collaborations Pharmaceuticals Inc.; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Thomas%2BR%2BLane%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Lane%20TR&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AThomas%2BR%2BLane%2B) Andre revnew 2 Ohio State University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Andre%2Brevnew%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=revnew%20A&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAndre%2Brevnew%2B) Craig A McElroy 5 College of Pharmacy, Ohio State University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Craig%2BA%2BMcElroy%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=McElroy%20CA&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ACraig%2BA%2BMcElroy%2B) * [ORCID record for Craig A McElroy](http://orcid.org/0000-0001-5950-0120 "Open in new tab") * For correspondence: mcelroy.31@osu.edu Christopher Hadad 6 Ohio State university * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Christopher%2BHadad%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Hadad%20C&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AChristopher%2BHadad%2B) * [Abstract](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5901254/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5901254/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5901254/1) * [Supplementary material](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.supplementary-material)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_data/node:5901254/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5901254/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract CYP1A2 contributes 13-15% of hepatic CYP450 content and plays a critical role in the metabolism of approximately 10% of pharmaceutical drugs in the human body. CYP1A2 has been previously reported to bioactivate and detoxify both the thion (P=S) and oxon (P=O) forms of organophosphorus (OP) compounds. In this study, we determined the capacity of CYP1A2 to degrade OP compounds using LC-MS/MS, as well as the inhibition of its activity by OP compounds using the previously developed pFluor50 assay. CYP1A2 was selective in metabolizing thions over oxons, and several OP compounds inhibited its activity in a time- and dose-dependent manner. To further investigate the mechanism of CYP1A2-OP interactions, molecular docking studies were performed using a crystal structure of CYP1A2 (PDB ID: 2HI4). Linear correlation analysis between CYP1A2 inhibition at 10 μM with 30 minute preincubation and the % OP compound remaining at 2 hours (R = -0.71, P The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. 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[ Download PDF](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.full.pdf) Print/Save Options [Download PDF](https://www.biorxiv.org/content/biorxiv/early/2026/10/25/2026.10.20.760143.full.pdf)Full Text & In-line FiguresXML [More Info](https://www.biorxiv.org/about/FAQ#PrintOptions "More Information on Print/Save Options") [Supplementary Material ](https://www.biorxiv.org/content/10.64898/2026.10.20.760143v1.supplementary-material) [ Email](https://www.biorxiv.org/ "Email this Article") [ Share](https://www.biorxiv.org/) Human CYP1A2 metabolism of organophosphorus pesticides and nerve agent surrogates Pratik Shriwas, Matthew Politeski,, Brian Scarpitti, Sean Ekins, Thomas R Lane, Andre revnew, Craig A McElroy, Christopher Hadad bioRxiv 2026.10.20.760143; doi: https://doi.org/10.64898/2026.10.20.760143 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. 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