Explore the foundational role ofLipinski's Rule of 5 (Ro5) in modern drug discovery and oral bioavailability prediction. Learn how core physicochemical parameters—including molecular weight, LogP, and hydrogen bond donors/acceptors—shape lead optimization. Discover how advanced cheminformatics, pKa prediction models, and AI-driven structure design engines empower researchers to successfully navigate complex "beyond Rule of 5" (bRo5) modalities like PROTACs, macrocycles, and covalent inhibitors without sacrificing safety or efficacy.