Advancing Drug Selectivity with Receptor.AI

The launch of our 5-Level Compound Selectivity Platform

Receptor.AI introduces a groundbreaking 5-Level Compound Selectivity Platform, redefining precision in drug discovery by targeting highly similar protein targets with unparalleled accuracy. This platform is engineered to meet the increasing demands for drugs that are ultra-selective to disease-related protein variants, minimizing adverse effects and paving the way for precision and individualized medicine.

The platform encompasses a series of technologically advanced levels, each designed to refine selectivity predictions for candidate compounds. Starting with a proteome-wide ranking, the process involves explicit screening against off-targets, AI-based prioritization of protein sequence differences, and extends to assessing protein structure differences on an atomic level. This meticulous approach ensures progressive accuracy and selectivity, facilitating the identification of ultra-selective small molecules for challenging targets, including those with no known ligands or ambiguous structures.

To validate this innovative platform, Receptor.AI embarked on extensive testing using proteins from the JAK and FGFR families, known for their significance in a range of diseases. The platform adeptly handled these proteins, demonstrating its capability to discriminate among highly similar variants, a testament to its precision and effectiveness.

Key to this process are:

- Level 1's proteome-wide ranking that initiates the selectivity prediction by screening ~100K compounds across ~9.3k proteins (Figure 1).

Figure 1. The architecture of 3DPROTDTA for activity prediction

- Level 2 focuses on explicit screening against defined off-target variants, filtering out non-selective compounds.

- Level 3 and 4 employ AI models to prioritize sequence and structural differences, respectively, fine-tuning the selectivity towards the target proteins (Figures 2 and 3 respectively).

Figure 2. AI-based prioritisation of protein sequence differences
Figure 3. Atomic-level selectivity DTI

- Level 5 introduces an innovative approach for targeting membrane proteins related to cancer, exploiting the unique composition of cancer cell membranes to achieve additional selectivity (Figure 4).

Figure 4. Development of membrane targeting drugs

The platform's efficacy was further underscored by benchmarking results showcasing its robust performance across all levels. Particularly noteworthy was its ability to differentiate among the subtle variations of JAK and FGFR proteins, affirming its potential in crafting ultra-selective molecules for complex targets.

In conclusion, Receptor.AI's 5-Level Compound Selectivity Platform stands as a monumental achievement in drug discovery, offering a sophisticated solution to the challenges of targeting similar protein variants. By leveraging this platform, Receptor.AI not only showcases its technological prowess but also its commitment to advancing the frontier of precision medicine, setting new standards for drug selectivity and efficacy.