Papaverine

Summary

Papaverine (CHEMBL19224) is an approved small-molecule vasodilator agent (ATC G04BE52) targeting PDE3A, PDE3B, and PDE10A; indicated across 7 conditions including erectile dysfunction and gastroenteritis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G04BE52 (+2 more)
• Targets: 3 (PDE3A, PDE3B, PDE10A)
• Indications: 7 conditions
• Clinical trials: 13
• Chemistry: 339.4 Da · C20H21NO4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL19224
Name	Papaverine
Type	Small molecule
Max phase	3
FDA approved	yes
PubChem CID	4680
ChEBI	CHEBI:28241
ATC	G04BE52, G04BE02, A03AD01
Molecular formula	C20H21NO4
Molecular weight	339.4
InChIKey	XQYZDYMELSJDRZ-UHFFFAOYSA-N

SMILES: COC1=C(C=C(C=C1)CC2=NC=CC3=CC(=C(C=C32)OC)OC)OC

IUPAC name: 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline

ChEBI definition: A benzylisoquinoline alkaloid that is isoquinoline substituted by methoxy groups at positions 6 and 7 and a 3,4-dimethoxybenzyl group at position 1. It has been isolated from Papaver somniferum.

Pharmacological roles (ChEBI): vasodilator agent, antispasmodic drug.

Also known as: NSC-136630, Papaverine, Papaverinum, papaverine, papaverin, SID11111623, SID11111624, SID11111625, SID50104295, SID90341237, SID124881091, PAPAVERINE

Parent form; salt/anhydrous children: CHEMBL98123, CHEMBL5278358

Patent coverage: 7,075 distinct patent families (22,172 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 21,767 (98%) 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
PDE3A	phosphodiesterase 3A	Inhibition	6.04	0.1%	Q14432
PDE3B	phosphodiesterase 3B	Inhibition	5.99	0.2%	Q13370
PDE10A	phosphodiesterase 10A	Inhibition	7.68	0.1%	Q9Y233

Broader ChEMBL bioactivity targets: 41 (assay-derived). Sample: Ubiquitin carboxyl-terminal hydrolase 2, Nuclear receptor ROR-gamma, Survival motor neuron protein, Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Thrombopoietin, Ras-related protein Rab-9A, ATP-binding cassette sub-family C member 4, cGMP-specific 3’,5’-cyclic phosphodiesterase.

Bioactivity

ChEMBL activities: 81 potent at pChembl ≥ 5 of 108 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
P51450	8.55	Potency	2.8	nM	CHEMBL_ACT_4972248
PDE10A	7.77	IC50	17	nM	CHEMBL_ACT_5127548
PDE10A	7.68	IC50	21	nM	CHEMBL_ACT_6337522
PDE10A	7.44	IC50	36	nM	CHEMBL_ACT_14650045
PDE10A	7.44	IC50	36	nM	CHEMBL_ACT_15151306
Q9QYJ6	7.44	IC50	36	nM	CHEMBL_ACT_16421368
Q9QYJ6	7.44	IC50	36	nM	CHEMBL_ACT_18657963
Q9QYJ6	7.44	IC50	36	nM	CHEMBL_ACT_18984741
PDE10A	7.44	IC50	36	nM	CHEMBL_ACT_19032237
PDE10A	7.44	IC50	36	nM	CHEMBL_ACT_24985001
Q9QYJ6	7.44	IC50	36	nM	CHEMBL_ACT_6337584
PDE10A	7.44	IC50	36	nM	CHEMBL_ACT_8047627
PDE10A	7.42	IC50	38	nM	CHEMBL_ACT_22905669
PDE10A	7.4	IC50	40	nM	CHEMBL_ACT_12157791
PDE10A	7.31	IC50	49	nM	CHEMBL_ACT_29311598
PDE10A	7.25	IC50	56.9	nM	CHEMBL_ACT_3310701
P08482	7.25	Potency	56.2	nM	CHEMBL_ACT_4811336
PDE10A	7.12	IC50	76	nM	CHEMBL_ACT_3310758
PDE10A	7.04	IC50	92.3	nM	CHEMBL_ACT_16491770
PDE10A	7.04	IC50	92.3	nM	CHEMBL_ACT_26105984
PDE10A	7.01	IC50	97	nM	CHEMBL_ACT_18984710
PDE10A	6.68	IC50	210	nM	CHEMBL_ACT_13419208
PDE10A	6.68	IC50	210	nM	CHEMBL_ACT_6212179
PDE3A	6.55	IC50	284	nM	CHEMBL_ACT_12157790
PDE3A	6.55	Ki	279	nM	CHEMBL_ACT_1803384
PDE3A	6.54	IC50	287	nM	CHEMBL_ACT_19052112
PDE3A	6.43	AC50	370	nM	CHEMBL_ACT_25190747
PDE3B	6.38	Ki	417	nM	CHEMBL_ACT_1803385
CREBBP	6.25	Potency	562.3	nM	CHEMBL_ACT_4773275
CREBBP	6.15	Potency	707.9	nM	CHEMBL_ACT_4773171

Target pathways

Aggregated over 3 target gene(s): PDE3A, PDE3B, PDE10A.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
G alpha (s) signalling events	3	PDE10A, PDE3A, PDE3B
PDE3B signalling	1	PDE3B
cGMP effects	1	PDE10A

Dominant GO biological processes

GO term	Targets
negative regulation of cAMP/PKA signal transduction	3
signal transduction	3
G protein-coupled receptor signaling pathway	2
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	2
oocyte maturation	1
lipid metabolic process	1
response to xenobiotic stimulus	1
regulation of meiotic nuclear division	1
negative regulation of apoptotic process	1
negative regulation of vascular permeability	1
positive regulation of vascular permeability	1
positive regulation of oocyte development	1
regulation of ribonuclease activity	1
cellular response to cGMP	1
cellular response to transforming growth factor beta stimulus	1

Indications & clinical

Indications

7 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
gastroenteritis	3	MONDO:0002269	EFO:1001463
non-small cell lung carcinoma	1	MONDO:0005233	EFO:0003060
lung neoplasm	1	MONDO:0021117	MONDO:0008903
benign prostatic hyperplasia	0	MONDO:0010811	EFO:0000284

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

Clinical trials

Total trials: 13.

Phase distribution

Phase	Trials
PHASE4	3
PHASE1	3
PHASE2	2
EARLY_PHASE1	2
Not specified	2
PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03894904	PHASE4	COMPLETED	Papaverine vs Heparin for Peripheral Arterial Catheter Patency in Pediatric Patients
NCT04162834	PHASE4	COMPLETED	Effect of Papaverine on Renal Artery Blood Flow Volume
NCT06550232	PHASE4	COMPLETED	IV PAPAVERINE Prior to Propess for Labor Induction
NCT02711241	PHASE3	TERMINATED	Optimal Analgesia in Acute Gastroenteritis
NCT00080808	PHASE2	COMPLETED	Nerve-Sparing Radical Prostatectomy With or Without Nerve Grafting Followed by Standard Therapy for Erectile Dysfunction in Treating Patients With Localized Prostate Cancer
NCT05861765	PHASE2	UNKNOWN	The Efficacy of Papaverine to Prevent Radial Artery Spasm During Transradial Cerebral Angiography
NCT03824327	PHASE1	ACTIVE_NOT_RECRUITING	Papaverine and Stereotactic Body Radiotherapy (SBRT) for Non Small Cell Lung Cancer (NSCLC) or Lung Metastases
NCT05136846	PHASE1	RECRUITING	Papaverine in Combination With Chemoradiation for the Treatment of Stage II-III Non-small Cell Lung Cancer
NCT06834126	PHASE1	RECRUITING	Papaverine in Combination With Radiation Therapy for the Treatment of Locally Advanced Rectal Cancer, DINOMITE Trial
NCT03064282	EARLY_PHASE1	UNKNOWN	Prostatic Hyperplasia Treatment and Cancer Prevention
NCT04030663	EARLY_PHASE1	COMPLETED	The Effect of Periradial Injection of Papaverine Versus Nitroglycerine on Radial Artery Diameter
NCT06547437	Not specified	NOT_YET_RECRUITING	Papaverine and Oxytocin vs Oxytocin Alone in Labor Induction
NCT07572461	Not specified	NOT_YET_RECRUITING	A Single-Arm, Prospective Study of Papaverine for the Treatment of Refractory Peripheral Neuropathy Induced by Taxane-Based Chemotherapy

Clinical evidence (CIViC)

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

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 0 clinical and 2 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

207 molecules share ≥1 primary target. Top 60 by shared-target count:

Molecule	Source	Status	Shared targets
SILDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE10A, PDE3A, PDE3B
VARDENAFIL	ChEMBL + PubChem	Phase 4 (approved)	PDE10A, PDE3A, PDE3B
DIPYRIDAMOLE	ChEMBL	Phase 4 (approved)	PDE10A, PDE3A, PDE3B
Tadalafil	PubChem	Approved	PDE10A, PDE3A, PDE3B
ANAGRELIDE	ChEMBL + PubChem	Phase 4 (approved)	PDE3A, PDE3B
LOSARTAN	ChEMBL + PubChem	Phase 4 (approved)	PDE3A, PDE3B
CILOSTAZOL	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
CRISABOROLE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
ENOXIMONE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
IBUDILAST	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
INAMRINONE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
MILRINONE	ChEMBL	Phase 4 (approved)	PDE3A, PDE3B
LEVOSIMENDAN	ChEMBL	Phase 3	PDE3A, PDE3B
ADIBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
BEMARINONE	ChEMBL	Phase 2	PDE3A, PDE3B
BEMORADAN	ChEMBL	Phase 2	PDE3A, PDE3B
CC-115	ChEMBL	Phase 2	PDE3A, PDE3B
CILOSTAMIDE	ChEMBL	Phase 2	PDE3A, PDE3B
ETAZOLATE	ChEMBL	Phase 2	PDE3A, PDE3B
IMAZODAN	ChEMBL	Phase 2	PDE3A, PDE3B
INDOLIDAN	ChEMBL	Phase 2	PDE3A, PDE3B
ISOMAZOLE	ChEMBL	Phase 2	PDE3A, PDE3B
LIXAZINONE	ChEMBL	Phase 2	PDE3A, PDE3B
MEDORINONE	ChEMBL	Phase 2	PDE3A, PDE3B
MERIBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
ORISMILAST	ChEMBL	Phase 2	PDE3A, PDE3B
OXAGRELATE	ChEMBL	Phase 2	PDE3A, PDE3B
PIMOBENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
PIROXIMONE	ChEMBL	Phase 2	PDE3A, PDE3B
QUAZINONE	ChEMBL	Phase 2	PDE3A, PDE3B
SIMENDAN	ChEMBL	Phase 2	PDE3A, PDE3B
SULMAZOLE	ChEMBL	Phase 2	PDE3A, PDE3B
VESNARINONE	ChEMBL	Phase 2	PDE3A, PDE3B
ZARDAVERINE	ChEMBL	Phase 2	PDE3A, PDE3B
CLOFARABINE	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
IDELALISIB	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
TAFAMIDIS	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
TAVABOROLE	ChEMBL + PubChem	Phase 4 (approved)	PDE3A
ACARBOSE	ChEMBL	Phase 4 (approved)	PDE3A
ADENOSINE	ChEMBL	Phase 4 (approved)	PDE3A
ALECTINIB	ChEMBL	Phase 4 (approved)	PDE3A
ALENDRONIC ACID	ChEMBL	Phase 4 (approved)	PDE3A
AMINOGLUTETHIMIDE	ChEMBL	Phase 4 (approved)	PDE3A
AMLEXANOX	ChEMBL	Phase 4 (approved)	PDE3A
ANTAZOLINE	ChEMBL	Phase 4 (approved)	PDE3A
ARIPIPRAZOLE	ChEMBL	Phase 4 (approved)	PDE3A
BENAZEPRIL	ChEMBL	Phase 4 (approved)	PDE3A
BENZBROMARONE	ChEMBL	Phase 4 (approved)	PDE3A
BITHIONOL	ChEMBL	Phase 4 (approved)	PDE3A
CABOZANTINIB	ChEMBL	Phase 4 (approved)	PDE3A
CALCITRIOL	ChEMBL	Phase 4 (approved)	PDE3A
CANDESARTAN CILEXETIL	ChEMBL	Phase 4 (approved)	PDE3A
CANNABIDIOL	ChEMBL	Phase 4 (approved)	PDE3A
CEFOPERAZONE	ChEMBL	Phase 4 (approved)	PDE3A
CHLORHEXIDINE	ChEMBL	Phase 4 (approved)	PDE3A
CHLOROQUINE	ChEMBL	Phase 4 (approved)	PDE3A
CHOLIC ACID	ChEMBL	Phase 4 (approved)	PDE3A
CINCHOPHEN	ChEMBL	Phase 4 (approved)	PDE10A
CINNARIZINE	ChEMBL	Phase 4 (approved)	PDE3A
CLADRIBINE	ChEMBL	Phase 4 (approved)	PDE3A