PDE4A phosphodiesterase 4A
ENSG00000065989 · protein coding · Open Targets profile
Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes. .
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 Withdrawn means the drug was pulled from the market or from development.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
- Approved Drug, Structure with Ligand, High-Quality Ligand, High-Quality Pocket, Druggable Family
- Antibody
- UniProt loc high conf, GO CC high conf, Human Protein Atlas loc
- PROTAC
- Literature, UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.284280002117157 (upper bound 0.4093700051307678). 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 176 registry trials, updated in the last three years, of the most advanced drugs against PDE4A (amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamole), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Hany F BadawyFaculty of Medicine, Beni-Suef University · 3 of 3 trials Phase 2+
- Clifton FullerM.D. Anderson Cancer Center · 2 of 2 trials Phase 2+
- Jaclyn TamaroffVanderbilt University Medical Center · 2 of 2 trials Phase 2+
- Kazuko MatsudaMediciNova, Inc. · 2 of 2 trials Phase 2+
- José M PalaciosProkreaBCN, S.L. · 1 of 2 trials Phase 2+
- Sherry McKeeYale University · 1 of 2 trials Phase 2+
- Adel Gaber BakrAssistant Professor of Pharmacology and Toxicology, Al-Azhar University (Boys, Assiut) · 1 of 1 trials Phase 2+
- ahmed abomandourDemonstrator of Clinical Pharmacy Department, Faculty of Pharmacy, Al-Azhar University (Boys, Assiut) · 1 of 1 trials Phase 2+
- Ahmed ElGhandourAssistant Professor of Internal Medicine and Gastroenterology, Faculty of Medicine, Ain-Shams University · 1 of 1 trials Phase 2+
- Amit SinglaRutgers University · 1 of 1 trials Phase 2+
- Andres FlotoCambridge Centre for Medical Research, Papworth Hospital · 1 of 1 trials Phase 2+
- Angela M CheungUniversity Health Network, Toronto · 1 of 1 trials Phase 2+
- Anirut PattaragarnSiriraj Hospital · 1 of 1 trials Phase 2+
- Azam ShafquatNational Institute of Cardiovascular Diseases (NICVD), Karachi, Pakistan · 1 of 1 trials Phase 2+
- Bao-Huan ZhouClinical Medical College of Yangzhou University · 1 of 1 trials Phase 2+
Registry trials of amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamole 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; 135 of 160 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. 16 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
63 trials of drugs against PDE4A were stopped early; 3 give no reason
Terminated, withdrawn and suspended interventional trials of amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamole, 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 63.
- terminated · 2026-11-03 · Philips Clinical & Medical Affairs Global · matched by the registry's drug synonyms“The study was stopped due to ongoing enrollment challenges.”
- terminated · 2026-08-04 · Genzyme, a Sanofi Company · matched by the registry's drug synonyms“Enrolment formally closed earlier than planned due to recruitment challenges.”
- terminated · 2026-06-30 · Hoffmann-La Roche · matched by the registry's drug synonyms“Sponsor decision to discontinue lebrikizumab development for the treatment of asthma.”
- withdrawn · 2025-05-31 · Cedars-Sinai Medical Center · Pentoxifylline Oral Product“Initially the study was underfunded; then, the device we planned to use was changed and the new pump significantly reduced hemolysis.”
- withdrawn · 2025-05-29 · Wake Forest University Health Sciences · matched by the registry's drug synonyms“Terminated IRB approval 6/26/2024, study was never initiated or activated”
- withdrawn · 2025-05-25 · National Institute of Cardiovascular Diseases, Pakistan · Aminophylline Injection“we could not find patients fulfilling all of our inclusion criteria”
- terminated · 2025-05-22 · Prokrea BCN, S.L. · matched by the registry's drug synonyms“The trial was teriminated early due to low subject recruitment and high screening failure rates, despite several protocol modifications.”
- withdrawn · 2025-03-13 · University of Nebraska · matched by the registry's drug synonyms“sponsor discontinued site participation”
- terminated · 2024-10-15 · University of Missouri-Columbia · Pentoxifylline“Placebo effect”
- terminated · 2024-09-25 · Iain Bressendorff · ACEi / ARB, SGLT2i, finerenone, semaglutide, pentoxifylline, hydrochlorthiazide, baricitinib“Slow recruitment”
- terminated · 2024-05-07 · University of Michigan · Amlexanox“Due to limited funding, trial was suspended, intending to restart with additional funds; then preliminary results were obtained, and research moved on to placebo controlled trial. Results for both have been published.”
- terminated · 2024-01-11 · Baylor College of Medicine · Pentoxifylline“Target enrollment was not reached because the medication, pentoxifylline, has a taste that is not well tolerated by infants. The study team decided to end the study before meeting the enrollment goal because of the medication taste.”
- terminated · 2023-11-07 · Clear Creek Bio, Inc. · Dipyridamole 75 MG“Low prevalence of COVID-19 in India led to lack of eligible subjects.”
- terminated · 2023-10-04 · Legacy Health System · matched by the registry's drug synonyms“Insufficient enrollment”
- terminated · 2023-08-31 · Boehringer Ingelheim · matched by the registry's drug synonyms“due to company decision”
- terminated · 2023-04-21 · UConn Health · Dipyridamole Tablets“reduction of Hospitalized COVID patients at UConnHealth”
- terminated · 2023-03-13 · Rush University Medical Center · Aminophylline“Due to nationwide shortage of Aminophylline. Enrolled subjects did not complete study.”
- withdrawn · 2023-02-02 · Rush University Medical Center · matched by the registry's drug synonyms“The P.I deceased.”
- withdrawn · 2023-01-18 · Sadat City University · Pentoxifylline“Institutional problems”
- withdrawn · 2023-01-11 · George Washington University · Apremilast 30mg“The principal investigator left George Washington University and closed the study at their departure.”
- withdrawn · 2022-08-01 · Henry Ford Health System · Pentoxifylline“Did not enroll”
- withdrawn · 2021-11-05 · University of California, Los Angeles · Theophylline ER“COVID-19”
- terminated · 2021-10-21 · Terence J. Coderre · matched by the registry's drug synonyms“Low recruitment due to the COVID-19 pandemic”
- withdrawn · 2021-10-11 · Rush University Medical Center · matched by the registry's drug synonyms“Due to nationwide shortage of Aminophylline. No subjects enrolled.”
- withdrawn · 2021-07-16 · The Hospital for Sick Children · matched by the registry's drug synonyms“Due to funding and Covid-19 pandemic”
Paediatric incentives and obligations for PDE4A's drugs
For amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamole: 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 · PDE4A 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 · EMA/PE/0000231892 (apremilast, Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and juvenile idiopathic arthritis)): PM: decision on the application for modification of an agreed PIP, 20 Mar 2025; EMEA-000715-PIP03-11-M06 (apremilast, Treatment of psoriasis): PM: decision on the application for modification of an agreed PIP, 1 Dec 2020; compliance positive 10 Nov 2023; EMEA-000715-PIP05-13-M05 (apremilast, Treatment of Behcet disease): PM: decision on the application for modification of an agreed PIP, 11 Aug 2022Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/22/2615 positive 16 May 2022: Treatment of fragile X syndrome; EU/3/16/1801 positive 12 Dec 2016: Treatment of amyotrophic lateral sclerosis; EU/3/13/1180 withdrawn 5 Aug 2013: Treatment of Behçet's DiseaseRule: 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 data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Apremilast Accord: authorised since 19 Apr 2024; Otezla: authorised since 15 Jan 2015; Ohtuvayre: application withdrawn; Apremilast Viatris: application withdrawnRule: 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 amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamoleRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 76 interventional studies of amlexanox, dyphylline, ibudilast, oxtriphylline, flavoxate, ensifentrine, apremilast, theophylline, drotaverine, aminophylline, pentoxifylline, dipyridamole include patients under 18; 15 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, 2026-11-11
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 28 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.