Avanafil

Summary

Avanafil (CHEMBL1963681) is an approved small-molecule EC 3.1.4.* (phosphoric diester hydrolase) inhibitor (ATC G04BE10); indicated across 3 conditions including erectile dysfunction and kidney disorder.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G04BE10
• Indications: 3 conditions
• Clinical trials: 24
• Chemistry: 483.9 Da · C23H26ClN7O3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1963681
Name	Avanafil
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	9869929
ChEBI	CHEBI:66876
ATC	G04BE10
Molecular formula	C23H26ClN7O3
Molecular weight	483.9
InChIKey	WEAJZXNPAWBCOA-INIZCTEOSA-N

SMILES: COC1=C(C=C(C=C1)CNC2=NC(=NC=C2C(=O)NCC3=NC=CC=N3)N4CCC[C@H]4CO)Cl

IUPAC name: 4-[(3-chloro-4-methoxyphenyl)methylamino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-N-(pyrimidin-2-ylmethyl)pyrimidine-5-carboxamide

ChEBI definition: A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 4-[(3-chloro-4-methoxybenzyl)amino]-2-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]pyrimidine-5-carboxylic acid with the amino group of pyrimidin-2-ylmethylamine. Used for treatment of erectile dysfunction.

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

Also known as: Avanafil, Avanafilo, Spedra, Stendra, TA-1790, AVANAFIL, SID165222624, avanafil, US9359371

Patent coverage: 1,365 distinct patent families (4,891 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,679 (96%) 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

Broader ChEMBL bioactivity targets: 2 (assay-derived). Sample: cGMP-specific 3’,5’-cyclic phosphodiesterase, cGMP-specific 3’,5’-cyclic phosphodiesterase.

Bioactivity

ChEMBL activities: 27 potent at pChembl ≥ 5 of 28 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE5A	8.3	Ki	5	nM	CHEMBL_ACT_18771534
O77746	8.28	IC50	5.2	nM	CHEMBL_ACT_14970070
PDE5A	8.15	IC50	6.99	nM	CHEMBL_ACT_17775452
PDE5A	8.07	IC50	8.56	nM	CHEMBL_ACT_17775451
PDE5A	8.03	IC50	9.29	nM	CHEMBL_ACT_17775431
PDE5A	7.97	IC50	10.77	nM	CHEMBL_ACT_17775439
PDE5A	7.97	IC50	10.77	nM	CHEMBL_ACT_17775440
PDE5A	7.97	IC50	10.77	nM	CHEMBL_ACT_17775441
PDE5A	7.97	IC50	10.77	nM	CHEMBL_ACT_17775442
PDE5A	7.97	IC50	10.77	nM	CHEMBL_ACT_17775443
PDE5A	7.91	IC50	12.25	nM	CHEMBL_ACT_17775429
PDE5A	7.9	IC50	12.53	nM	CHEMBL_ACT_17775438
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775430
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775432
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775433
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775434
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775435
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775436
PDE5A	7.76	IC50	17.32	nM	CHEMBL_ACT_17775437
PDE5A	7.68	IC50	20.86	nM	CHEMBL_ACT_17775444
PDE5A	7.68	IC50	20.86	nM	CHEMBL_ACT_17775445
PDE5A	7.68	IC50	20.86	nM	CHEMBL_ACT_17775446
PDE5A	7.68	IC50	20.86	nM	CHEMBL_ACT_17775447
PDE5A	7.58	IC50	26.04	nM	CHEMBL_ACT_17775448
PDE5A	7.58	IC50	26.04	nM	CHEMBL_ACT_17775449
PDE5A	7.58	IC50	26.04	nM	CHEMBL_ACT_17775450
PDE5A	5.28	IC50	5200	nM	CHEMBL_ACT_22878830

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

3 indications (2 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
kidney disorder	1	MONDO:0005240	EFO:0003086

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

Clinical trials

Total trials: 24.

Phase distribution

Phase	Trials
PHASE1	11
PHASE3	7
PHASE4	5
PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01698684	PHASE4	COMPLETED	Research Evaluating a PDE5 Inhibitor for Erectile Dysfunction
NCT01768676	PHASE4	COMPLETED	Study Evaluating the Effects of Avanafil on Semen Parameters
NCT02033200	PHASE4	COMPLETED	Safety Study Looking at the Effects of Stendra on Vision
NCT03169582	PHASE4	UNKNOWN	Avanafil Versus Sildenafil in Spinal Cord Injury Erectile Dysfunction
NCT04374994	PHASE4	COMPLETED	Daily Avanafil for Erectile Dysfunction
NCT00790751	PHASE3	COMPLETED	Research Evaluating an Investigational Medication for Erectile Dysfunction - General ED
NCT00809471	PHASE3	COMPLETED	Research Evaluating an Investigational Medication for Erectile Dysfunction - Diabetic ED (REVIVE-D)
NCT00853606	PHASE3	COMPLETED	Long-Term Safety and Efficacy Study of Avanafil in Men With Erectile Dysfunction
NCT00895011	PHASE3	COMPLETED	Research Evaluating an Investigational Medication for Erectile Dysfunction - Post-Prostatectomy
NCT00903981	PHASE3	COMPLETED	Therapeutic Confirmatory Study to Evaluate the Efficacy and Safety of Avanafil
NCT01705197	PHASE3	COMPLETED	This Study is to Evaluate the Safety and Efficacy of Avanafil in the Treatment of Erectile Dysfunction.
NCT02503306	PHASE3	COMPLETED	Efficacy and Tolerability Study of Avanafil in Russia
NCT02477436	PHASE2	COMPLETED	Efficacy and Safety of Avanafil in the Patients With Erectile Dysfunction
NCT00769041	PHASE1	COMPLETED	A Thorough EKG Safety Study of TA-1790 (Avanafil)
NCT00770042	PHASE1	COMPLETED	To Evaluate The Effect Of Ketoconazole, Ritonavir and Erythromycin on the Safety and Pharmacokinetics of Avanafil
NCT00914511	PHASE1	COMPLETED	A Pharmacokinetic Study of Avanfil in Healthy Young Male Subjects
NCT01054261	PHASE1	COMPLETED	To Compare the Pharmacokinetics of Avanafil in Subjects With Mild and Moderate Renal Impairment to Subjects With Normal Renal Function.
NCT01054430	PHASE1	COMPLETED	To Assess the Safety of Avanafil in Healthy and Hepatically Impaired Male Subjects.
NCT01054859	PHASE1	COMPLETED	A Phase I Crossover Study of the Hemodynamic Interactions of Avanafil & Alcohol in Healthy Male Subjects.
NCT01095588	PHASE1	COMPLETED	Study the Effect of Avanafil on the Pharmacodynamics and Pharmacokinetics of Warfarin in Healthy Male Subjects
NCT01095601	PHASE1	COMPLETED	Assess the Effect of Food on Avanafil Pharmacokinetic (PK), to Compare 2 Oral Formulations of Avanafil,and Investigate Dose Proportionality in Healthy Male Subjects
NCT01100021	PHASE1	COMPLETED	Hemodynamic Study of Avanafil and Two α-Adrenergic Blockers,Doxazosin and Tamsulosin
NCT01117038	PHASE1	COMPLETED	Drug Interaction Study of Avanafil and Enalapril or Amlodipine
NCT01616485	PHASE1	COMPLETED	Study to Evaluate Hemodynamic Response to to a Sublingual Dose of Glyceryl Trinitrate in Subjects Receiving TA-1790, Sildenafil Citrate, and Placebo

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).