01568nas a2200193   4500000000100000008004100001260001500042100001700057700001700074700002000091700001700111700001700128245005000145856007200195300001400267490000800281520107100289022001401360       2026                            d  c2026-04-021 aWenqiang Liu1 aPaul D. Pang1 aCatherine A. Wu1 aDanilo Tagle1 aJoseph C. Wu00aNew approach methodologies for drug discovery  uhttps://www.sciencedirect.com/science/article/pii/S0092867426002175  a1877-19030 v1893 aTraditional animal-based drug discovery has high failure rates, prompting the search for and adoption of human-centered new approach methodologies (NAMs). Rapid advances in stem cell-, organoid-, and in silico-based NAMs, supported by evolving frameworks from the National Institutes of Health (NIH) and the Food and Drug Administration (FDA), now span the entire drug-discovery continuum, from disease modeling and drug design to efficacy testing. Our review highlights recent progress across these domains, including the identification of therapeutic candidates, the development of cutting-edge models and technologies, and the potential of NAMs themselves as treatments in preclinical and clinical contexts, while examining the key biological, technical, and regulatory bottlenecks that need to be addressed to enable robust translational adoption. We conclude by discussing the translational and societal considerations essential to the responsible adoption of NAMs and outlining future human-centric pipelines poised to redefine the landscape of drug discovery.  a0092-8674