Table 1 |.
Drug discovery routes from zebrafish to the clinic
| Drug | Zebrafish screening assay | Indication | Status; clinical trial identifier |
|---|---|---|---|
| New applications for known targets | |||
| MEK inhibitor | Prevent lymphatic disease in ARAF-mutant transgenic model | Lymphatic disease | Compassionate use |
| MAPK pathway inhibitors | Rescue blood flow in BRAF-mutant transgenic model | Arteriovenous malformation | Compassionate use, planned clinical trials |
| Leflunomide | Inhibit neural crest development | Melanoma | Phase I (on hold); NCT01611675 |
| All-trans retinoic acid | Pluripotent zebrafish blastomere culture | Adenoid cystic carcinoma | Phase II; NCT03999684 |
| Olaparib plus temozolomide | Adult PDX and xenograft models | Rhabdomyosarcoma | Phase I; NCT01858168 |
| New target or new application | |||
| ProHema (PGE2 derivative) | HSC expansion in development | Leukaemia, graft versus host disease | Phase II; NCT01627314, NCT00890500 |
| Clemizole (EPX-100) and clemizole derivatives (EPX-101, EPX-102, EPX-103) | Rescue of seizures in scn1lab mutant | Dravet syndrome | Phase II; NCT04462770 |
| Trifluoperazine | Rescue of anaemia in rsp19 mutants | Diamond Blackfan anaemia | Phase I; NCT03966053 |
| New chemical entity | |||
| ORC-13661 | Protection of lateral line hair cells from cisplatin and aminoglycoside | Hearing loss following antibiotic treatment in patients with CF | Phase II |
| KER-047 | Dorsalization of developing embryo | Fibrodysplasia ossificans progressiva; iron deficiency anaemia; iron-refractory iron deficiency anaemia | Phase I; ACTRN12619000319178 |
| PP2A activator | Selective toxicity for MYC-overexpressing thymocytes | T cell acute lymphoblastic leukaemia | Preclinical |
CF, cystic fibrosis; HSC, haematopoietic stem cell; PDX, patient-derived xenograft; PGE2, prostaglandin E2; PP2A, protein phosphatase 2A.