Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel “first-in-class” anti-inflammatory drug candidates: a reviewer’s perspective

摘要: Inflammation is a complex, metabolically expensive process involving multiple signaling pathways and regulatory mechanisms which have evolved over evolutionary timescale. Addressing targets of inflammation holistically, in moderation, probably more evolutionarily viable strategy, as compared to current therapy addresses drug isolation. Polypharmacology, addressing targets, commonly used complex ailments, suggesting the superior safety efficacy profile multi-target (MT) drugs. Phenotypic discovery, generated successful MT first-in-class drugs past, now re-emerging. A multi-pronged approach, modulates conserved, robust pervasive cellular tissue repair, with AMPK at helm, regulating metabolic/immune/redox underlying inflammation, perhaps strategy than single Molecules that modulate molecular moderation (modulating TH cells toward anti-inflammatory phenotype, activating AMPK, stimulating Nrf2 inhibiting NFκB) might serve model for novel Darwinian “first-in-class” therapeutic category holistically immune, redox metabolic processes associated inflammatory repair. Such multimodal biological activity supported by fact several non-calorific pleiotropic natural products action been incorporated into diet (chiefly guided adaptive development olfacto-gustatory preferences timescales) rendering such molecules, endowed privileged scaffolds, naturally oriented targets.