{"doi":"10.3389/fddsv.2026.1777138","title":"Fundamentals of dermatologic drug discovery","abstract":"<jats:p>Advances in cutaneous immunology, human genetics, and molecular pharmacology have transformed the dermatologic treatment landscape, yet translation from biologic insight to effective therapy remains uneven. Skin disease creates development challenges that generic drug-discovery frameworks often underemphasize. These include the skin barrier, differences between epidermal, dermal, follicular, and systemic disease biology, overlapping inflammatory and neuroimmune pathways, and the need for endpoints that capture both visible disease and patient symptoms. Programs can fail despite persuasive biology when cutaneous exposure is inadequate, local tolerability is unacceptable, endpoints are insensitive, or the selected route and modality are poorly matched to disease severity and intended clinical use. A dermatology-specific approach is presented for target identification, modality and delivery selection, translational evidence generation, and early clinical proof-of-concept. Core principles include human-relevant target validation, explicit positioning of targets within the disease process, early alignment of mechanism with delivery strategy, early integration of skin-specific pharmacokinetic and pharmacodynamic tools, and selection of translational models according to the decision they are intended to inform. This primer is intended for translational scientists, clinician-investigators, and drug developers seeking guidance specific to skin disease rather than templates adapted from other therapeutic areas.</jats:p>","journal":"Frontiers in Drug Discovery","year":2026,"id":655354,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":250839,"name":"Ayman Grada","orcid":"0000-0002-5321-0584","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Fundamentals of dermatologic drug discovery","abstract":"<jats:p>Advances in cutaneous immunology, human genetics, and molecular pharmacology have transformed the dermatologic treatment landscape, yet translation from biologic insight to effective therapy remains uneven. Skin disease creates development challenges that generic drug-discovery frameworks often underemphasize. These include the skin barrier, differences between epidermal, dermal, follicular, and systemic disease biology, overlapping inflammatory and neuroimmune pathways, and the need for endpoints that capture both visible disease and patient symptoms. Programs can fail despite persuasive biology when cutaneous exposure is inadequate, local tolerability is unacceptable, endpoints are insensitive, or the selected route and modality are poorly matched to disease severity and intended clinical use. A dermatology-specific approach is presented for target identification, modality and delivery selection, translational evidence generation, and early clinical proof-of-concept. Core principles include human-relevant target validation, explicit positioning of targets within the disease process, early alignment of mechanism with delivery strategy, early integration of skin-specific pharmacokinetic and pharmacodynamic tools, and selection of translational models according to the decision they are intended to inform. This primer is intended for translational scientists, clinician-investigators, and drug developers seeking guidance specific to skin disease rather than templates adapted from other therapeutic areas.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19162232","pmcid":null,"openalex_id":"https://openalex.org/W7167953323","authors":[],"funders":[],"total_grants":0,"fwci":0.0,"citation_percentile":0.80420215,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2026.1777138/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/journals/drug-discovery/articles/10.3389/fddsv.2026.1777138/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fddsv.2026.1777138/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fddsv.2026.1777138","host_type":"journal"},{"url":"https://doaj.org/article/26a334fe465240eb848cfb23ab9832d1","host_type":"repository"}],"fields_of_study":["Psoriasis: Treatment and Pathogenesis","Cutaneous lymphoproliferative disorders research","Autoimmune Bullous Skin Diseases"],"mesh_terms":[],"keywords":["Disease","Tolerability","Clinical trial","Translational research","Drug","Bench to bedside","Drug discovery","Clinical disease","Drug development"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T10:34:51.083400Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}