Icariin

Summary

Icariin (CHEMBL553204) is a phase-3 clinical-stage small-molecule bone density conservation agent targeting PDE5A.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 1 (PDE5A)
• Clinical trials: 3
• Chemistry: 676.7 Da · C33H40O15

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL553204
Name	Icariin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	5318997
ChEBI	CHEBI:78420
Molecular formula	C33H40O15
Molecular weight	676.7
InChIKey	TZJALUIVHRYQQB-XLRXWWTNSA-N

SMILES: C[C@H]1[C@@H]([C@H]([C@H]([C@@H](O1)OC2=C(OC3=C(C2=O)C(=CC(=C3CC=C(C)C)O[C@H]4[C@@H]([C@H]([C@@H]([C@H](O4)CO)O)O)O)O)C5=CC=C(C=C5)OC)O)O)O

IUPAC name: 5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one

ChEBI definition: A member of the class of flavonols that is kaempferol which is substituted at position 8 by a 3-methylbut-2-en-1-yl group and in which the hydroxy groups at positions 3, 4’, and 7 have been converted to the corresponding 6-deoxy-α-L-mannopyranoside, methyl ether, and β-D-glucopyranoside, respectively. A phoshphodiesterase-5 inhibitor, it is obtained from several species of plants in the genus Epimedium and is thought to be the main active ingredient of the Chinese herbal medicine Herba Epimedii (yinyanghuo).

Pharmacological roles (ChEBI): bone density conservation agent, phytoestrogen, EC 3.1.4.35 (3’,5’-cyclic-GMP phosphodiesterase) inhibitor, antioxidant.

Also known as: Epimedii herba icariin, Icariin, icariin, SID26719816, ICARIIN, C0164748

Patent coverage: 2,676 distinct patent families (4,951 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 4,947 (100%) 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	5.23	0%	O76074

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: cGMP-specific 3’,5’-cyclic phosphodiesterase, DNA polymerase beta, Lysine-specific histone demethylase 1A.

Bioactivity

ChEMBL activities: 1 potent at pChembl ≥ 5 of 3 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
PDE5A	5.23	IC50	5900	nM	CHEMBL_ACT_2232585

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

0 indications (0 at ChEMBL trial phase 4).

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE3	1
PHASE1	1
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01979133	PHASE3	COMPLETED	Study of Icariin for Bipolar Disorder and Co-Occurring Substance Use Disorders
NCT02112123	PHASE1	COMPLETED	Icariin to Prevent Corticosteroid-related Memory Changes
NCT07076784	Not specified	COMPLETED	Topical Icariin on Acne and Acne Scars

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
VARDENAFIL	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
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