PPIA peptidylprolyl isomerase A
ENSG00000196262 · protein coding · Open Targets profile
Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, High-Quality Ligand, Med-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Half-life Data, Small Molecule Binder
- Other modalities
- Approved Drug
gnomAD loss of function constraint: o/e 0.13043999671936035 (upper bound 0.41060999035835266). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 273 registry trials, updated in the last three years, of the most advanced drugs against PPIA (cyclosporine, alisporivir, scy 635), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Andromachi ScaradavouMemorial Sloan Kettering Cancer Center · 2 of 2 trials Phase 2+
- Bhavisha A PatelNational Heart, Lung, and Blood Institute (NHLBI) · 2 of 2 trials Phase 2+
- Jun ShiInstitute of Hematology & Blood Diseases Hospital, China · 2 of 2 trials Phase 2+
- Paola CastellaniZambon SpA, Chief Medical Officer and R&D · 2 of 2 trials Phase 2+
- yongrong laiFirst Affiliated Hospital of Guangxi Medical University · 2 of 2 trials Phase 2+
- Xiaojun HuangPeking University People's Hospital · 1 of 2 trials Phase 2+
- Aaron FriedmanUniversity of Minnesota · 1 of 1 trials Phase 2+
- Agnès HartmannAPHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS · 1 of 1 trials Phase 2+
- Alain FISCHERAssistance Publique - Hôpitaux de Paris · 1 of 1 trials Phase 2+
- Alberto Sanchez-FueyoKing's College London · 1 of 1 trials Phase 2+
- Alessandro RambaldiHematology Unit - Ospedali Riuniti BG · 1 of 1 trials Phase 2+
- Anbin HuangUnion Hospital, Tongji Medical College, Huazhong University of Science and Technology · 1 of 1 trials Phase 2+
- André TichelliUniversity Hospital, Basel, Switzerland · 1 of 1 trials Phase 2+
- Andrea BacigalupoFondazione Policlinico Universitario Agostino Gemelli IRCCS · 1 of 1 trials Phase 2+
- Ann DahlbergFred Hutch/University of Washington Cancer Consortium · 1 of 1 trials Phase 2+
Registry trials of cyclosporine, alisporivir, scy 635 updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 212 of 244 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 29 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
175 trials of drugs against PPIA were stopped early; 24 give no reason
Terminated, withdrawn and suspended interventional trials of cyclosporine, alisporivir, scy 635, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 175.
- terminated · 2026-11-04 · Institute of Hematology & Blood Diseases Hospital, China · matched by the registry's drug synonyms“No significant improvement in efficacy was observed.”
- terminated · 2026-10-19 · Boston Children's Hospital · cyclosporine“Funding terminated”
- withdrawn · 2026-10-16 · Anjali Sharathkumar · matched by the registry's drug synonyms“Withdrawn in HawkIRB”
- withdrawn · 2026-06-04 · Peking Union Medical College Hospital · cyclosporine“This is a duplicate registration. The research plan and content have already been updated in another entry.”
- withdrawn · 2026-06-04 · Peking Union Medical College Hospital · matched by the registry's drug synonyms“The registration of this research plan was incorrect. A new registration has been re-applied for.”
- withdrawn · 2026-06-04 · Peking Union Medical College Hospital · Cyclosporine (CsA)“The registration of this research plan was incorrect. A new registration has been re-applied for.”
- terminated · 2026-05-20 · Masonic Cancer Center, University of Minnesota · Cyclosporine A“No longer a research question to answer.”
- terminated · 2026-05-14 · Fred Hutchinson Cancer Center · Cyclosporine“Study was terminated prior to enrolling protocol target accrual goal due to declining accrual and Data Safety Monitoring Board recommendations.”
- terminated · 2026-04-24 · European Society for Blood and Marrow Transplantation · matched by the registry's drug synonyms“Ceased production of the study drug, Lymphoglobulin. Recruitment of patients onto the trial was too slow.”
- terminated · 2026-04-07 · Zambon SpA · Liposomal Cyclosporine A 5 mg, Liposomal Cyclosporine A 10 mg“Study was terminated for business reasons. The earlier study end is not related to any safety concerns or data issues identified at any site or within the overall study data collected to date.”
- terminated · 2026-03-30 · Assistance Publique - Hôpitaux de Paris · matched by the registry's drug synonymsNo reason given
- terminated · 2025-12-09 · Peking Union Medical College Hospital · cyclosporine“insufficient patient enrollment”
- terminated · 2025-10-21 · Incyte Corporation · matched by the registry's drug synonyms“Study terminated by sponsor”
- terminated · 2025-10-02 · St. Jude Children's Research Hospital · Cyclosporine“Principal Investigator left institution”
- terminated · 2025-07-18 · AHS Cancer Control Alberta · matched by the registry's drug synonyms“Slow patient accrual and appearance of a toxicity”
- withdrawn · 2025-07-16 · Virginia G. Kaklamani · matched by the registry's drug synonyms“Unable to enroll to study.”
- terminated · 2025-06-29 · M.D. Anderson Cancer Center · Cyclosporine“PI Request”
- terminated · 2025-03-14 · Charite University, Berlin, Germany · matched by the registry's drug synonyms“Insufficient patient recruitment”
- terminated · 2025-02-06 · Atrial Fibrillation Network · matched by the registry's drug synonyms“following a recommendation from the data safety and monitoring board due to safety concerns and a tendency towards futility.”
- terminated · 2025-01-07 · Dompé Farmaceutici S.p.A · matched by the registry's drug synonyms“Taking into account that 5 out of 22 patients in the Reparixin group experienced EAD during the first stage of the study, according to the Protocol and the DMC conclusion, it was decided on the early termination of the study”
- withdrawn · 2024-11-07 · LEO Pharma · Cyclosporine A“Strategic decision”
- terminated · 2024-11-01 · Astellas Pharma China, Inc. · matched by the registry's drug synonyms“Due to difficulty enrolling patients”
- withdrawn · 2024-10-26 · M.D. Anderson Cancer Center · matched by the registry's drug synonyms“No participants enrolled.”
- terminated · 2024-10-22 · Armando Torres Ramírez · matched by the registry's drug synonyms“Terminated: higher rate of acute rejection in the Cyclosporin A group”
- terminated · 2024-03-07 · King's College London · Tacrolimus, cyclosporine and/or mycophenolic acid, mycophenolate mofetil or azathioprine“Primary endpoint not reached.”
Paediatric incentives and obligations for PPIA's drugs
For cyclosporine, alisporivir, scy 635: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PPIA is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-000724-PIP02-11 (alisporivir, Treatment of chronic hepatitis C): W: decision granting a waiver in all age groups for all conditions or indications, 4 Jul 2012Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000724-PIP02-11, 2026-11-11
- EU orphan designation: yes · EU/3/22/2590 positive 16 Mar 2022: Treatment of collagen VI-related myopathiesRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/22/2590, 2026-11-11
- Authorised in the EU: no · EMA lists no centrally authorised medicine of cyclosporine, alisporivir, scy 635Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of cyclosporine, alisporivir, scy 635Rule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 421 interventional studies of cyclosporine, alisporivir, scy 635 include patients under 18; 51 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 3 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| CYCLOSPORINE | Protein | phase 4 | dry eye syndrome, psoriasis, keratitis, keratoconjunctivitis, inflammation, rheumatoid arthritis, graft versus host disease, psoriasis vulgaris, +175 more | Open Targets · ChEMBL |
| ALISPORIVIR | Protein | phase 3 | hepatitis C virus infection, COVID-19 | Open Targets · ChEMBL |
| SCY 635 | Protein | phase 2 | hepatitis C virus infection | Open Targets · ChEMBL |