Spermidine

Summary

Spermidine (CHEMBL19612) is a phase-3 clinical-stage small-molecule geroprotector targeting KCNJ2 and KCNJ4; indicated across 1 condition including hypertensive disorder.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Targets: 2 (KCNJ2, KCNJ4)
• Indications: 1 condition
• Clinical trials: 10
• Chemistry: 145.25 Da · C7H19N3

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL19612
Name	Spermidine
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	1102
ChEBI	CHEBI:16610
Molecular formula	C7H19N3
Molecular weight	145.25
InChIKey	ATHGHQPFGPMSJY-UHFFFAOYSA-N

SMILES: C(CCNCCCN)CN

IUPAC name: N’-(3-aminopropyl)butane-1,4-diamine

ChEBI definition: A triamine that is the 1,5,10-triaza derivative of decane.

Pharmacological roles (ChEBI): geroprotector, autophagy inducer.

Other ChEBI roles (chemical / environmental): fundamental metabolite.

Also known as: Spermidine, spermidine, SID11111787, SID11113819, SID90340561, SID124881418, Spermidin, SPERMIDINE

Parent form; salt/anhydrous children: CHEMBL1256356, CHEMBL1473196

Patent coverage: 19,575 distinct patent families (63,007 SureChEMBL compound mentions), from 1 matched compound structure(s). 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
KCNJ2	Kir2.1	Antagonist	8.1	0%	P63252
KCNJ4	Kir2.3	Antagonist		4.4%	P48050

Broader ChEMBL bioactivity targets: 22 (assay-derived). Sample: Pyruvate kinase PKM, Thrombopoietin, Thyrotropin receptor, Carbonic anhydrase 2, Carbonic anhydrase 13, Carbonic anhydrase 7, Carbonic anhydrase 1, Muscarinic acetylcholine receptor M1, Serine/threonine-protein kinase mTOR, Carbonic anhydrase 3.

Bioactivity

ChEMBL activities: 14 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CA4	6.95	Ki	112	nM	CHEMBL_ACT_3395221
CA14	6	Ki	1000	nM	CHEMBL_ACT_3395229
CA2	5.96	Ki	1110	nM	CHEMBL_ACT_3395219
CA5A	5.91	Ki	1220	nM	CHEMBL_ACT_3395222
CA7	5.91	Ki	1230	nM	CHEMBL_ACT_3395225
CA9	5.86	Ki	1370	nM	CHEMBL_ACT_3395226
PKM	5.85	IC50	1410	nM	CHEMBL_ACT_24813478
CA1	5.85	Ki	1400	nM	CHEMBL_ACT_3395218
CA6	5.85	Ki	1410	nM	CHEMBL_ACT_3395224
CA5B	5.84	Ki	1440	nM	CHEMBL_ACT_3395223
THPO	5.2	Potency	6310	nM	CHEMBL_ACT_4809535
THPO	5.2	Potency	6310	nM	CHEMBL_ACT_5074242
P08482	5.05	Potency	8912	nM	CHEMBL_ACT_4857815
Q99N23	5	Ki	10000	nM	CHEMBL_ACT_3395230

Target pathways

Aggregated over 2 target gene(s): KCNJ2, KCNJ4.

Top Reactome pathways

18 total, by targets touching each:

Pathway	Targets	Genes
Neurotransmitter receptors and postsynaptic signal transmission	2	KCNJ2, KCNJ4
Transmission across Chemical Synapses	2	KCNJ2, KCNJ4
Neuronal System	2	KCNJ2, KCNJ4
Activation of G protein gated Potassium channels	2	KCNJ2, KCNJ4
Classical Kir channels	2	KCNJ2, KCNJ4
G protein gated Potassium channels	2	KCNJ2, KCNJ4
Inwardly rectifying K+ channels	2	KCNJ2, KCNJ4
Potassium Channels	2	KCNJ2, KCNJ4
Muscle contraction	2	KCNJ2, KCNJ4
Phase 4 - resting membrane potential	2	KCNJ2, KCNJ4
Cardiac conduction	2	KCNJ2, KCNJ4
GABA receptor activation	2	KCNJ2, KCNJ4
GABA B receptor activation	2	KCNJ2, KCNJ4
Activation of GABAB receptors	2	KCNJ2, KCNJ4
Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits	2	KCNJ2, KCNJ4
Sensory Perception	1	KCNJ2
Sensory perception of taste	1	KCNJ2
Sensory perception of sour taste	1	KCNJ2

Dominant GO biological processes

GO term	Targets
potassium ion transport	2
regulation of monoatomic ion transmembrane transport	2
potassium ion import across plasma membrane	2
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
regulation of skeletal muscle contraction via regulation of action potential	1
magnesium ion transport	1
intracellular potassium ion homeostasis	1
protein homotetramerization	1
relaxation of cardiac muscle	1
regulation of resting membrane potential	1
regulation of membrane repolarization	1
cellular response to mechanical stimulus	1
potassium ion transmembrane transport	1
cardiac muscle cell action potential involved in contraction	1

Indications & clinical

Indications

1 indication (0 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
hypertensive disorder	3	MONDO:0005044	EFO:0000537

Clinical trials

Total trials: 10.

Phase distribution

Phase	Trials
Not specified	5
PHASE4	1
PHASE3	1
PHASE2	1
PHASE1/PHASE2	1
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT06792916	PHASE4	RECRUITING	This Study Evaluates the Clinical Effect of Adding Spermidine Gel to Minimally Invasive Non-surgical Periodontal Therapy (MINST) to Improve Periodontal Health.
NCT04405388	PHASE3	UNKNOWN	Spermidine Anti-Hypertension Study
NCT06186102	PHASE2	ACTIVE_NOT_RECRUITING	Polyamine Treatment in Elderly Patients With Coronary Artery Disease
NCT07035626	PHASE1/PHASE2	RECRUITING	A Randomized Controlled Trial of Spermidine for the Prevention of Radiation-Induced Xerostomia in Head and Neck Squamous Cell Carcinoma (Including Nasopharyngeal Carcinoma)
NCT07058974	PHASE1	RECRUITING	A Study of Exercise and Pharmacologic Intervention on Systemic Inflammation
NCT05459961	Not specified	ACTIVE_NOT_RECRUITING	Metabolic Responses to Spermidine Supplementation.
NCT06017219	Not specified	ACTIVE_NOT_RECRUITING	Bioavailability of Spermidine in Healthy Males
NCT07202403	Not specified	ENROLLING_BY_INVITATION	Iterative Design Trial to Assess Dietary Supplements and Other Aging-targeted Therapies
NCT07383311	Not specified	RECRUITING	Autophagy-Enhancers to Reduce Sleep Disturbances
NCT05017428	Not specified	COMPLETED	Absorption and Digestion Kinetics of Human Metabolites

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
Belzutifan	PubChem	Approved	KCNJ2
Propafenone	PubChem	Approved	KCNJ2
Zuranolone	PubChem	Approved	KCNJ2