Title: Phronesis AI: Accelerating Drug Discovery with Cutting-Edge AI Technology
Executive Summary
Phronesis AI is a pioneering drug discovery company that offers pharmaceutical companies’ state-of-the-art AI software for fully autonomous de novo drug design and screening. Our mission is to lower the cost and accelerate the drug discovery process, making more treatments available to people faster and more affordably. By leveraging our proprietary LIME (Learning Iteratively through Molecular Evolution) process, Phronesis AI can deliver promising drug candidates faster and more efficiently than traditional methods. The company's collaborations with leading research institutions and our recent validation study highlight the potential of our AI platform to transform the drug discovery process.
It is our goal to offer cutting-edge, comprehensive services that include novel drug discovery, profiling, synthetic feasibility assessments, and fast chemical synthesis for carefully selected molecules, all in one convenient and easy to use location.
Introduction
Phronesis AI is an innovative private drug discovery company focused on providing innovative pharmaceutical software for fully autonomous de novo drug design and screening. Our goal is to lower the cost and accelerate the drug discovery process, making more treatments available to people faster and more affordably. By harnessing the power of artificial intelligence, Phronesis AI's proprietary LIME (Learning Iteratively through Molecular Evolution) process enables the rapid and efficient design and optimization of novel drugs for a wide range of diseases.
Technology Overview: LIME Drug Design Process
The LIME process consists of the following steps:
1. An initial subset of structural starting points is chosen from Phronesis AI's proprietary database.
2. These molecules are analyzed automatically using optimized virtual screening software.
3. The top-scoring molecules are selected based entirely on user-defined design objectives.
4. The molecules and their detailed analysis are saved to the database and used for subsequent training.
5. Novel molecules are produced by fine-tuning the molecular generation process.
6. The novel molecules are iteratively screened and added to the database alongside known molecules.
7. This optimization process is repeated autonomously and completed over the course of approximately 3 days.
As part of the design process, chemical synthetic feasibility, number of synthetic steps, and starting materials are also predicted.
Validation: LIME's Success in Generating De Novo Inhibitors
Phronesis AI used our LIME process to generate de novo inhibitors of the SARS-CoV-2 papain-like protease (i.e., PLpro). Out of the 54 analog molecules selected for synthesis and testing, 21 showed strong or modest binding activity, with 13 having high mean T pm values (binding) and variable selectivity. Five of these candidates demonstrated relatively good binding and promising specificity.
A direct comparison of a representative compound (PAI-CSEMRS-1376) from the top 5 candidates with a known PLpro inhibitor (XR8-89) revealed several advantages. Both compounds had comparable consensus LogP values, high predicted GI absorption, and good bioavailability. However, PAI-CSEMRS-1376 was not a Pgp substrate, unlike XR8-89, which is predicted to be a Pgp substrate. Pgp (P-glycoprotein) is a cell membrane protein that functions as an efflux pump, expelling foreign substances from the cell. Being a Pgp substrate may affect a drug's absorption and distribution, potentially reducing its effectiveness. Additionally, both compounds were substrate inhibitors of CYP-3A4, a major and important subtype. CYP-3A4 is a cytochrome P450 enzyme involved in the metabolism of a substantial number of drugs. Inhibition of CYP-3A4 can lead to altered drug metabolism and possible drug-drug interactions.
Our COVID-SARS-2 compounds have received further validation through the favorable response of esteemed institutions such as SCRIPPS and the University of Texas, who are interested in co-venturing and further developing this project.
Collaborations and Partnerships
Phronesis AI collaborates with several esteemed research institutions, including Johns Hopkins University (JHU), the University of California, Irvine (UCI), the University of Kentucky, and the University of California, San Diego (UCSD). These collaborations focus on various diseases and research areas:
1. JHU: Heart Failure
2. UCI: Huntington's Disease
3. University of Kentucky: In the process of validating molecules, with a potential paper on the results if successful breast cancer
4. UCSD: Custom project
5. HER2 Breast, Brain, and Lung Cancers: Preliminary results from a Twitter project show strong candidates, but these results are only for screening and have not yet been validated in vitro or via ADMET testing.
Conclusions
Phronesis AI's ground-breaking LIME process has demonstrated its potential to revolutionize the drug discovery process. By utilizing artificial intelligence, the company can create more effective treatments faster, more efficiently, and more affordably than traditional methods. Our collaborations with leading research institutions and ongoing validation efforts underscore the power of our AI platform to transform the pharmaceutical industry.
Let us discover the possibilities together.
Contact us for more information: contact@phronesisai.com
Take away points
Phronesis AI is well-positioned to make a significant impact in the drug discovery landscape. With our advanced AI-driven LIME process, strong collaborations with leading research institutions, and ongoing validation efforts, the company is poised to accelerate the development of new treatments for a wide range of diseases. By lowering the cost and reducing the time required for drug discovery, Phronesis AI aims to improve the availability and affordability of life-saving medications for patients worldwide.
Phronesis AI's unique one stop shopping approach to drug discovery and our commitment to innovation make us a valuable partner for pharmaceutical companies looking to harness the power of artificial intelligence in our quest to develop new treatments. By working together, Phronesis AI and our partners can unlock the full potential of AI-driven drug discovery and help shape the future of medicine.
March 28, 2023