PDE3A phosphodiesterase 3A
ENSG00000172572 · protein coding · Open Targets profile
Cyclic nucleotide phosphodiesterase with specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:1315035, PubMed:25961942, PubMed:8155697, PubMed:8695850). Also has activity toward cUMP (PubMed:27975297). Independently of its catalytic activity it is part of an E2/17beta-estradiol-induced pro-apoptotic signaling pathway. E2 stabilizes the PDE3A/SLFN12 complex in the cytosol, promoting the dephosphorylation of SLFN12 and activating its pro-apoptotic ribosomal RNA/rRNA ribonuclease activity. This apoptotic pathway might be relevant in tissues with high concentration of E2 and be for instance involved in placenta remodeling (PubMed:31420216, PubMed:34707099). {ECO:0000269|PubMed:1315035, ECO:0000269|PubMed:25961942, ECO:0000269|PubMed:27975297, ECO:0000269|PubMed:31420216, ECO:0000269|PubMed:34707099, ECO:0000269|PubMed:8155697, ECO:0000269|PubMed:8695850}.
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 Withdrawn means the drug was pulled from the market or from development.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, Druggable Family
- Antibody
- UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.4373599886894226 (upper bound 0.563979983329773). 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 132 registry trials, updated in the last three years, of the most advanced drugs against PDE3A (inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifylline), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Clifton FullerM.D. Anderson Cancer 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+
- Adel Gaber BakrAssistant Professor of Pharmacology and Toxicology, Al-Azhar University (Boys, Assiut) · 1 of 1 trials Phase 2+
- Agnieszka TycińskaMedical University of Bialystok · 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+
- Albert CastellheimQueen Silvia Children´s Hospital, Department of anesthesia and intensive care · 1 of 1 trials Phase 2+
- André DenaultMontreal Heart Institute · 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+
- Aurélien MAZERAUDAnesthésie - Réanimation GHU Paris - Neuro Sainte-Anne · 1 of 1 trials Phase 2+
- Belaid BB BouhemadUniversity Hospital of Dijon · 1 of 1 trials Phase 2+
- Ben SafaSunnybrook Health Sciences Centre · 1 of 1 trials Phase 2+
- Benjamin BC ChoustermanHôpital Lariboisière, Paris (AP-HP) · 1 of 1 trials Phase 2+
Registry trials of inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifylline 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; 114 of 127 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. 5 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
48 trials of drugs against PDE3A were stopped early; 5 give no reason
Terminated, withdrawn and suspended interventional trials of inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifylline, 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 48.
- 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 · 2026-09-28 · Centre Hospitalier Universitaire Dijon · Levosimendan“There was insufficient funding to continue the study in good conditions.”
- 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.”
- 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.”
- suspended · 2025-05-14 · Sclnow Biotechnology Co., Ltd. · matched by the registry's drug synonyms“Others”
- terminated · 2025-05-11 · Peng Roc Chen, MD · matched by the registry's drug synonyms“Slow enrollment”
- terminated · 2025-05-09 · Medical University of Bialystok · Levosimendan“The level of recruitment, 62 participants enrolled, does not allow for achieving the protocol-defined target of 350 participants by the end of the recruitment period.”
- terminated · 2024-10-23 · Niguarda Hospital · matched by the registry's drug synonyms“Because the Data Safety Monitoring Board after the interim analisys concluded that the experimental treatment is not proviiding any minimal full benefit compared to the contrtol. They then reccomended to stop the trial due to futility”
- 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 · 2024-01-11 · 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 · 2023-10-04 · Legacy Health System · matched by the registry's drug synonyms“Insufficient enrollment”
- terminated · 2023-03-09 · Orion Corporation, Orion Pharma · Levosimendan“This was an open label extension for patients completing the REFALS study (3119002; NCT03505021). Study 3119002 showed lack of efficacy of ODM109 so the sponsor decided to terminate this 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 · 2022-10-27 · RWTH Aachen University · Levosimendan“Rationale obsolete”
- withdrawn · 2022-08-01 · Henry Ford Health System · Pentoxifylline“Did not enroll”
- terminated · 2022-01-13 · Rijnstate Hospital · Enoximone“A limited number of inclusions due to the Covid-pandemic”
- terminated · 2021-11-19 · Incyte Corporation · Anagrelide“Enrollment issues”
- terminated · 2021-10-21 · Terence J. Coderre · matched by the registry's drug synonyms“Low recruitment due to the COVID-19 pandemic”
- terminated · 2021-06-29 · French Innovative Leukemia Organisation · Anagrelide“not enough recruitment”
- withdrawn · 2021-02-02 · MetroHealth Medical Center · Pentoxifylline“Study not selected to receive funding”
- terminated · 2019-09-13 · Tampere University Hospital · levosimendan“Change of schedule”
- terminated · 2019-07-02 · Indiana University · Milrinone“Completion not feasible due to lack of eligible subjects.”
- terminated · 2019-05-29 · Patrick Northup, MD · matched by the registry's drug synonyms“Poor enrollment of study population”
Paediatric incentives and obligations for PDE3A's drugs
For inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifylline: 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 · PDE3A 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-000720-PIP01-09-M02 (anagrelide, Treatment of essential thrombocythaemia): PM: decision on the application for modification of an agreed PIP, 19 Dec 2013; compliance positive 14 Feb 2014Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-000720-PIP01-09-M02, 2026-11-11
- EU orphan designation: yes · EU/3/22/2615 positive 16 May 2022: Treatment of fragile X syndrome; EU/3/18/1980 withdrawn 22 Feb 2018: Treatment of amyotrophic lateral sclerosis; EU/3/16/1801 positive 12 Dec 2016: Treatment of amyotrophic lateral sclerosis; EU/3/00/010 expired 30 Dec 2000: Treatment of essential thrombocythaemiaRule: 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 · Anagrelide Viatris (previously Anagrelide Mylan): authorised since 15 Feb 2018; Ohtuvayre: application withdrawn; Xagrid: authorised since 15 Nov 2004Rule: 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 inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifyllineRule: 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 · 50 interventional studies of inamrinone, anagrelide, enoximone, ensifentrine, oxtriphylline, ibudilast, milrinone lactate, dyphylline, inamrinone lactate, milrinone, levosimendan, pentoxifylline include patients under 18; 4 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 18 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.