Vardenafil

Summary

Vardenafil (CHEMBL1520) is an approved small-molecule vasodilator agent (ATC G04BE09) targeting PDE5A; indicated across 8 conditions including erectile dysfunction and pulmonary hypertension.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G04BE09
• Targets: 1 (PDE5A)
• Indications: 8 conditions
• Clinical trials: 23
• Chemistry: 488.6 Da · C23H32N6O4S

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1520
Name	Vardenafil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	135400189
ChEBI	CHEBI:46295
ATC	G04BE09
Molecular formula	C23H32N6O4S
Molecular weight	488.6
InChIKey	SECKRCOLJRRGGV-UHFFFAOYSA-N

SMILES: CCCC1=NC(=C2N1N=C(NC2=O)C3=C(C=CC(=C3)S(=O)(=O)N4CCN(CC4)CC)OCC)C

IUPAC name: 2-[2-ethoxy-5-(4-ethylpiperazin-1-yl)sulfonylphenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one

ChEBI definition: The sulfonamide resulting from formal condensation of the sulfo group of 4-ethoxy-3-(5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(1H)-one-2-yl)benzenesulfonic acid and the secondary amino group of 4-ethylpiperazine.

Pharmacological roles (ChEBI): vasodilator agent, EC 3.1.4.* (phosphoric diester hydrolase) inhibitor.

Also known as: BAY-389456, Levitra, Vardenafil, Vivanza, SID50112786, vardenafil, VARDENAFIL, SID174007044, Vardernafil, VARDENAFIL HYDROCHLORIDE

Parent form; salt/anhydrous children: CHEMBL1339, CHEMBL1874590, CHEMBL2106480, CHEMBL5715931

Patent coverage: 5,106 distinct patent families (21,078 SureChEMBL compound mentions), from 4 matched compound structure(s). One matched structure accounts for 19,932 (95%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
PDE5A	phosphodiesterase 5A	Inhibition	9.7	0%	O76074

Broader ChEMBL bioactivity targets: 21 (assay-derived). Sample: cGMP-specific 3’,5’-cyclic phosphodiesterase, Voltage-dependent L-type calcium channel subunit alpha-1C, Amine oxidase [flavin-containing] A, A-type voltage-gated potassium channel KCND3, Phosphodiesterase 4, Phosphodiesterase 3, Phosphodiesterase 1, Phosphodiesterase 6, Muscarinic acetylcholine receptor M2, Phosphodiesterase 7.

Bioactivity

ChEMBL activities: 30 potent at pChembl ≥ 5 of 40 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE5A	10.54	IC50	0.03	nM	CHEMBL_ACT_22791907
PDE5A	9.77	IC50	0.17	nM	CHEMBL_ACT_18126527
PDE5A	9.7	IC50	0.2	nM	CHEMBL_ACT_1520505
PDE5A	9.3	IC50	0.5	nM	CHEMBL_ACT_18528107
PDE5A	9.15	Ki	0.7	nM	CHEMBL_ACT_18771535
PDE5A	9.15	IC50	0.71	nM	CHEMBL_ACT_2567002
PDE5A	9.15	IC50	0.7	nM	CHEMBL_ACT_574531
PDE5A	9.05	IC50	0.89	nM	CHEMBL_ACT_16755421
PDE5A	9.05	IC50	0.89	nM	CHEMBL_ACT_18549360
PDE5A	9	IC50	1	nM	CHEMBL_ACT_12680586
PDE5A	9	Ki	1	nM	CHEMBL_ACT_1506645
PDE6D	9	IC50	1	nM	CHEMBL_ACT_1520506
PDE6D	7.96	IC50	11	nM	CHEMBL_ACT_12680582
PDE6D	7.96	IC50	11	nM	CHEMBL_ACT_1506646
PDE11A	6.89	IC50	130	nM	CHEMBL_ACT_1520501
PDE1A	6.64	IC50	230	nM	CHEMBL_ACT_1520499
PDE11A	6.62	IC50	240	nM	CHEMBL_ACT_12680577
PDE1A	6.52	IC50	300	nM	CHEMBL_ACT_12680576
PDE9A	6.34	IC50	460	nM	CHEMBL_ACT_1520509
PDE3B	6.24	IC50	580	nM	CHEMBL_ACT_12680584
PDE9A	6.17	IC50	680	nM	CHEMBL_ACT_12680579
PDE10A	6.1	IC50	790	nM	CHEMBL_ACT_1520500
PDE10A	6.06	IC50	880	nM	CHEMBL_ACT_12680578
ADORA1	6	AC50	1010	nM	CHEMBL_ACT_25202515
PDE7A	5.72	IC50	1900	nM	CHEMBL_ACT_12680581
PDE3B	5.68	IC50	2100	nM	CHEMBL_ACT_1520503
PDE2A	5.51	IC50	3100	nM	CHEMBL_ACT_12680585
PDE4A	5.42	IC50	3800	nM	CHEMBL_ACT_12680583
PDE4A	5.35	IC50	4500	nM	CHEMBL_ACT_1520504
PDE4A	5.03	AC50	9384	nM	CHEMBL_ACT_25207287

Target pathways

Aggregated over 1 target gene(s): PDE5A.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
cGMP effects	1	PDE5A
Smooth Muscle Contraction	1	PDE5A
RHOBTB1 GTPase cycle	1	PDE5A

Dominant GO biological processes

GO term	Targets
signal transduction	1
cGMP catabolic process	1
negative regulation of cAMP/PKA signal transduction	1

Indications & clinical

Indications

8 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
erectile dysfunction	4	MONDO:0005362	EFO:0004234
pulmonary hypertension	3	MONDO:0005149	MONDO:0005149
Raynaud disease	2	MONDO:0008364	EFO:1001145
benign prostatic hyperplasia	2	MONDO:0010811	EFO:0000284
overactive bladder	2	MONDO:0006624	EFO:1000781
cystic fibrosis	2	MONDO:0009061	MONDO:0009061
ischemia reperfusion injury	1	MONDO:0005203	EFO:0002687

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 23.

Phase distribution

Phase	Trials
PHASE4	9
PHASE2	4
PHASE1	3
Not specified	3
PHASE3	1
PHASE2/PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00379756	PHASE4	COMPLETED	A Study Evaluating Vardenafil Compared to Placebo in Subjects With Erectile Dysfunction (ED) and Dyslipidemia
NCT00498680	PHASE4	UNKNOWN	Safety and Clinical Effectiveness of 2 Lower Dose Combined PDE5i’s vs. Single Maximal Dose PDE5i
NCT00705588	PHASE4	UNKNOWN	Long Acting Phosphodiesterase 5 Inhibitors as Add-on Therapy for Patients With Pulmonary Hypertension Treated With Prostanoids.
NCT00725790	PHASE4	UNKNOWN	A Study to Evaluate the Efficacy and Safety of Vardenafil in Men With Erectile Dysfunction Caused by Spinal Cord Injury
NCT00853840	PHASE4	COMPLETED	Study To Investigate The Hemodynamic Effects Of Single Dose Vardenafil In Subjects Receiving Maraviroc
NCT01084187	PHASE4	COMPLETED	Correlation Study of Vascular Parameters in Hypertensive Men With Erectile Dysfunction
NCT01649739	PHASE4	UNKNOWN	Vardenafil as add-on Therapy for Patients With Pulmonary Hypertension Treated With Inhaled Iloprost
NCT02344823	PHASE4	UNKNOWN	Effect of Vardenafil on Erectile Dysfunction and Portal Hemodynamics in Patients With Liver Cirrhosis
NCT02450188	PHASE4	COMPLETED	Vardenafil and Cognitive-behavioral Sex Therapy for the Treatment of Erectile Dysfunction (STEDOV)
NCT00718952	PHASE3	COMPLETED	The Efficacy and Safety of Vardenafil in the Treatment of Pulmonary Arterial Hypertension
NCT01291199	PHASE2/PHASE3	COMPLETED	Effects of Vardenafil on Clinical Symptoms and Peripheral Blood Flow in Patients With Raynaud’s Syndrome
NCT00478881	PHASE2	COMPLETED	A Study To Assess If 10 mg Vardenafil (BAY38-9456) Taken Twice Daily For 6 Weeks Has An Effect On Bladder Function
NCT01002534	PHASE2	TERMINATED	Does a Nasal Instillation of Vardenafil Normalize the Nasal Potential Difference in Cystic Fibrosis Patients?
NCT01168817	PHASE2	COMPLETED	Clinical Proof-of-concept Study for the Combination BAY60-4552 / Vardenafil for the Treatment of Erectile Dysfunction Not Sufficiently Responsive to Standard Therapy With PDE5 Inhibitors
NCT02219646	PHASE2	COMPLETED	Diabetes & Vardenafil
NCT06860399	PHASE1/PHASE2	COMPLETED	Vardenafil Vs Sildenafil for the Treatment of Pulmonary Hypertension of the Newborn
NCT01110590	PHASE1	COMPLETED	Multiple Dose Escalation Study (14 Days) to Investigate Safety, Tolerability, PK and PD of Vardenafil and BAY60-4552
NCT01260285	PHASE1	COMPLETED	The Safety of Vardenafil in Patients Undergoing Cardiac Surgery
NCT05567367	PHASE1	COMPLETED	A Healthy Volunteer Study Evaluating the the Safety, Tolerability, and Pharmacokinetics of RT234
NCT02279992	EARLY_PHASE1	TERMINATED	Pilot Study of Vardenafil and Carboplatin in Patients With Gliomas and Brain Metastases
NCT00517179	Not specified	COMPLETED	Effect of Vardenafil on Blood Pressure in Patients With Erectile Dysfunction Who Received Concomitant Doxazosin GITS
NCT00909233	Not specified	COMPLETED	LEVITRA® 20mg Special Drug Use Investigation (Long-term)
NCT01406535	Not specified	TEMPORARILY_NOT_AVAILABLE	Improvement of Myocardial Blood Flow by PhosphoDiesterase 5 Inhibition in Coronary Artery Disease

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

25 molecules share ≥1 primary target. Top 25 by shared-target count:

Molecule	Source	Status	Shared targets
SILDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE5A
TADALAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE5A
AVANAFIL	ChEMBL	Phase 4 (approved)	PDE5A
CELECOXIB	ChEMBL	Phase 4 (approved)	PDE5A
DIPYRIDAMOLE	ChEMBL	Phase 4 (approved)	PDE5A
DONEPEZIL	ChEMBL	Phase 4 (approved)	PDE5A
IBUDILAST	ChEMBL	Phase 4 (approved)	PDE5A
MILRINONE	ChEMBL	Phase 4 (approved)	PDE5A
PALBOCICLIB	ChEMBL	Phase 4 (approved)	PDE5A
TANNIC ACID	ChEMBL	Phase 4 (approved)	PDE5A
ICARIIN	ChEMBL	Phase 3	PDE5A
ICARITIN	ChEMBL	Phase 3	PDE5A
PAPAVERINE	ChEMBL	Phase 3	PDE5A
UDENAFIL	ChEMBL	Phase 3	PDE5A
CARTAZOLATE	ChEMBL	Phase 2	PDE5A
CILOSTAMIDE	ChEMBL	Phase 2	PDE5A
CIPAMFYLLINE	ChEMBL	Phase 2	PDE5A
GISADENAFIL	ChEMBL	Phase 2	PDE5A
ISOMAZOLE	ChEMBL	Phase 2	PDE5A
MIRODENAFIL	ChEMBL	Phase 2	PDE5A
PF-00489791	ChEMBL	Phase 2	PDE5A
PF-03049423	ChEMBL	Phase 2	PDE5A
ROLIPRAM	ChEMBL	Phase 2	PDE5A
SULMAZOLE	ChEMBL	Phase 2	PDE5A
ZAPRINAST	ChEMBL	Phase 2	PDE5A