OncoSignal
Live from Open Targets Platform, fetched 2026-11-12 01:52 UTC. Every row links to its source record.

PDE5A phosphodiesterase 5A

ENSG00000138735 · protein coding · Open Targets profile

Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides. This phosphodiesterase catalyzes the specific hydrolysis of cGMP to 5'-GMP (PubMed:15489334, PubMed:9714779). Specifically regulates nitric-oxide- generated cGMP (PubMed:15489334). {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9714779}.

8 of the 13 drugs recorded against PDE5A are approved

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.

8 small molecule drugs at Approved: VARDENAFIL HYDROCHLORIDE, IBUDILAST, SILDENAFIL CITRATE, AVANAFIL, UDENAFIL, DIPYRIDAMOLE, TADALAFIL, PENTOXIFYLLINE3 small molecule drugs at Phase 2: GISADENAFIL, PF-00489791, PF-030494232 small molecule drugs at Withdrawn: SILDENAFIL, VARDENAFILSmall molecule 13Approved 8Phase 2 3Withdrawn 2

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 Withdrawn means the drug was pulled from the market or from development.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.

PDE5A: inherited and tumour-mutation evidence across 15 cancers

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.

Inherited (germline) variantsMutations in tumours (somatic)
00.250.50.751benign prostatic hyperplasiabenign prostatic hyperplasianon-small cell lung carcinomanon-small cell lung carcinomaacute lymphoblastic leukemiaacute lymphoblastic leukemiabreast cancerbreast cancerfibrosisfibrosismelanomamelanomapancreatic adenocarcinomapancreatic adenocarcinomacolorectal carcinomacolorectal carcinomaglioblastomaglioblastomabreast carcinomabreast carcinomahead and neck squamous cell carcinomahead and neck squamous cell carcinomacolorectal cancercolorectal cancerplasma cell myelomaplasma cell myelomapancreatic neoplasmpancreatic neoplasmmalignant pancreatic neoplasmmalignant pancreatic neoplasm

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
PROTAC
Database Ubiquitination, Small Molecule Binder

gnomAD loss of function constraint: o/e 0.6079300045967102 (upper bound 0.7450100183486938). 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 251 registry trials, updated in the last three years, of the most advanced drugs against PDE5A (vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, PF-00489791, PF-03049423), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.

111 of 228 trials of drugs against PDE5A have sites only in countries outside the US, China, Europe and Japan

Registry trials of vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, PF-00489791, PF-03049423 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; 211 of 228 have all sites in one country.

Sites only in this groupSites here and elsewhere
United StatesUnited States: 62 trials with sites only hereUnited States: 11 trials with sites here and elsewhere73ChinaChina: 11 trials with sites only hereChina: 2 trials with sites here and elsewhere13EuropeEurope: 30 trials with sites only hereEurope: 5 trials with sites here and elsewhere35JapanJapan: 1 trials with sites only hereJapan: 1 trials with sites here and elsewhere2OtherOther: 111 trials with sites only hereOther: 13 trials with sites here and elsewhere124

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. 23 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.

132 trials of drugs against PDE5A were stopped early; 10 give no reason

Terminated, withdrawn and suspended interventional trials of vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, PF-00489791, PF-03049423, 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 132.

  • terminated · 2026-11-04 · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Sildenafil
    “Results of interim analysis”
  • 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.”
  • suspended · 2026-09-28 · University of Miami · tadalafil
    “The sponsor has communicated that they may no longer fund this research study. Pending final confirmation if the study will be closed.”
  • terminated · 2026-02-23 · National Cancer Institute (NCI) · tadalafil
    “Study was terminated due to poor accrual.”
  • withdrawn · 2025-09-16 · University of Alabama at Birmingham · Sildenafil 50 mg Oral Tablet
    “Funding not obtained”
  • withdrawn · 2025-09-16 · University of Alabama at Birmingham · Sildenafil 50 mg Oral Tablet
    “Funding not obtained”
  • withdrawn · 2025-07-14 · Sadat City University · Sildenafil Citrate
    “Institutional and funding constrains”
  • withdrawn · 2025-07-14 · Sadat City University · Tadalafil 5Mg Tab
    “Institutional and funding constrains”
  • 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.”
  • terminated · 2025-02-04 · Actelion · Sildenafil
    “Terminated due to slow enrollment”
  • withdrawn · 2024-12-06 · Universidad del Norte · Sildenafil Injectable Product
    “The study did not begin due to lack of resources for its execution.”
  • 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”
  • withdrawn · 2024-05-16 · University of British Columbia · Sildenafil
    “iss”
  • terminated · 2024-02-28 · Uniformed Services University of the Health Sciences · Sildenafil Citrate 50Mg Tab
    “funding ran out after unanticipated length of time ( for IRB approval, CRADA, and start letter”
  • terminated · 2024-02-20 · Nanjing First Hospital, Nanjing Medical University · Sildenafil
    “Lack of subjects.”
  • 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 · 2023-10-31 · University of Mississippi Medical Center · Sildenafil 100 mg
    “Despite significant effort, we were unable to obtain the supply of drugs and supplements needed for the various arms of this Clinical Trial.”
  • terminated · 2023-10-04 · Legacy Health System · matched by the registry's drug synonyms
    “Insufficient enrollment”
  • withdrawn · 2023-08-15 · University of Nebraska · Sildenafil citrate
    “PI decision”
  • withdrawn · 2023-06-26 · University of New Mexico · Sildenafil
    “The project was not funded and could not be initiated.”
  • withdrawn · 2023-05-15 · University Hospital, Montpellier · Sildenafil
    “New sponsor”
  • terminated · 2023-04-21 · UConn Health · Dipyridamole Tablets
    “reduction of Hospitalized COVID patients at UConnHealth”
Paediatric incentives and obligations for PDE5A's drugs

For vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, PF-00489791, PF-03049423: 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.

  • EU paediatric investigation plan: yes · EMA/PE/0000183373 (tadalafil;tamsulosin, Treatment of benign prostatic hyperplasia): W: decision granting a waiver in all age groups for all conditions or indications, 6 Dec 2024; EMA/PE/0000181891 (sildenafil citrate;testosterone, Treatment of hypoactive sexual desire disorder): W: decision granting a waiver in all age groups for all conditions or indications, 25 Oct 2024; EMEA-003323-PIP01-22 (tadalafil;Finasteride, Treatment of benign prostatic hyperplasia): W: decision granting a waiver in all age groups for all conditions or indications, 13 Apr 2023; EMEA-003261-PIP01-22 (Finasteride;tadalafil, Treatment of patients with benign prostatic hyperplasia): W: decision granting a waiver in all age groups for all conditions or indications, 28 Oct 2022; +3 more
    Rule: 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/3/23/2831 positive 13 Oct 2023: Treatment of Leigh syndrome; 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/3/10/815 positive 26 Nov 2010: treatment of postcardiotomy right ventricular failure; +3 more
    Rule: 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 · Revatio: authorised since 28 Oct 2005; Viagra: authorised since 13 Sept 1998; Mysildecard: authorised since 15 Sept 2016; Spedra: authorised since 21 Jun 2013; +15 more
    Rule: 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 link
    Rule: 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 vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, pf-00489791, pf-03049423
    Rule: 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 · 141 interventional studies of vardenafil, ibudilast, sildenafil, avanafil, udenafil, dipyridamole, tadalafil, pentoxifylline, gisadenafil, pf-00489791, pf-03049423 include patients under 18; 12 are recruiting, not yet recruiting or active
    Rule: 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 13 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.

DrugTypeHighest stageIndicationsSource records
VARDENAFIL HYDROCHLORIDESmall moleculeapprovalerectile dysfunctionOpen Targets · ChEMBL
IBUDILASTSmall moleculeapprovalGiant Lymph Node Hyperplasia, Airway obstruction, amyotrophic lateral sclerosis, long COVID-19, alcohol dependence, methamphetamine dependence, multiple sclerosis symptom measurement, opiate dependence, +10 moreOpen Targets · ChEMBL
SILDENAFIL CITRATESmall moleculephase 4erectile dysfunction, pulmonary arterial hypertension, connective tissue disorder, congestive heart failure, fetal growth restriction, COVID-19, perinatal asphyxia, Fetal distress, +22 moreOpen Targets · ChEMBL
AVANAFILSmall moleculephase 4erectile dysfunctionOpen Targets · ChEMBL
UDENAFILSmall moleculephase 4erectile dysfunction, pulmonary hypertension, chronic obstructive pulmonary disease, heart failure, systolic heart failure, Alzheimer disease, Raynaud disease, pulmonary arterial hypertension, +1 moreOpen Targets · ChEMBL
DIPYRIDAMOLESmall moleculephase 4coronary artery disorder, stroke disorder, Recurrent thrombophlebitis, hypertensive disorder, cervical artery dissection, ischemic stroke, transient ischemic attack, myocardial infarction, +15 moreOpen Targets · ChEMBL
TADALAFILSmall moleculephase 4erectile dysfunction, pulmonary arterial hypertension, benign prostatic hyperplasia, dysuria, pulmonary hypertension, diabetes mellitus, lower urinary tract symptom, Raynaud disease, +47 moreOpen Targets · ChEMBL
PENTOXIFYLLINESmall moleculephase 4cardiovascular disorder, intermittent vascular claudication, liver failure, cirrhosis of liver, chronic kidney disease, kidney disorder, rapidly progressive glomerulonephritis, Proteinuria, +80 moreOpen Targets · ChEMBL
GISADENAFILSmall moleculephase 2erectile dysfunction, lower urinary tract symptom, overactive bladder, chronic obstructive pulmonary diseaseOpen Targets · ChEMBL
PF-00489791Small moleculephase 2chronic obstructive pulmonary disease, Raynaud disease, hypertensive disorder, essential hypertension, pulmonary arterial hypertensionOpen Targets · ChEMBL
PF-03049423Small moleculephase 2ischemic strokeOpen Targets · ChEMBL
SILDENAFILSmall moleculewithdrawalerectile dysfunction, pulmonary hypertension, pulmonary arterial hypertension, Eisenmenger syndrome, heart failure, congestive heart failure, diabetes mellitus, chronic lung disease, +83 moreOpen Targets · ChEMBL
VARDENAFILSmall moleculewithdrawalerectile dysfunction, major depressive disorder, depressive disorder, pulmonary arterial hypertension, benign prostatic hyperplasia, lower urinary tract symptom, Raynaud disease, overactive bladder, +6 moreOpen Targets · ChEMBL