XtalPi leveraged its AI-driven platform and quantum physics-based Free Energy Perturbation (FEP) methods to discover novel non-covalent small molecule inhibitors targeting GPX4, a crucial enzyme in cellular antioxidant defense, which had no previously reported reference compound. Over 28 days, the team tackled the challenge of GPX4’s shallow and flat binding pocket, utilizing AI and automation to predict key pharmacophores from a 6.4 x 10¹⁴ accessible space and rapidly synthesizing a focused library, ultimately discovering inhibitors with promising potency. This case validates the power of XtalPi’s AI drug discovery platform in identifying novel hit compounds for a new biological target.