Quinine

Summary

Quinine (CHEMBL170) is an approved small-molecule non-narcotic analgesic (ATC M09AA72) targeting SLC29A4, KCNK18, and KCNB2; indicated across 5 conditions including malaria and plasmodium falciparum malaria.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: M09AA72 (+1 more)
• Targets: 5 (SLC29A4, KCNK18, KCNB2…)
• Indications: 5 conditions
• Clinical trials: 24
• Chemistry: 324.4 Da · C20H24N2O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL170
Name	Quinine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3034034
ChEBI	CHEBI:15854
ATC	M09AA72, P01BC01
Molecular formula	C20H24N2O2
Molecular weight	324.4
InChIKey	LOUPRKONTZGTKE-WZBLMQSHSA-N

SMILES: COC1=CC2=C(C=CN=C2C=C1)[C@H]([C@@H]3C[C@@H]4CCN3C[C@@H]4C=C)O

IUPAC name: (R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methanol

ChEBI definition: A cinchona alkaloid that is cinchonidine in which the hydrogen at the 6-position of the quinoline ring is substituted by methoxy.

Pharmacological roles (ChEBI): antimalarial, muscle relaxant, non-narcotic analgesic.

Also known as: Chininum purum, NSC-192949, Quinine, Rezquin, WR297608, quinine, Quinine salt, GNF-Pf-180, SID144205942, QUININE, SID170465032, Quinine hemisulfate

Parent form; salt/anhydrous children: CHEMBL588046, CHEMBL589001, CHEMBL1201100, CHEMBL1899143, CHEMBL2146083, CHEMBL2146084, CHEMBL2146088, CHEMBL2146105, CHEMBL2359966, CHEMBL3229759, CHEMBL3229764, CHEMBL3706390, CHEMBL3707252, CHEMBL3707329, CHEMBL3707332

Patent coverage: 34,239 distinct patent families (108,216 SureChEMBL compound mentions), from 2 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
SLC29A4	Plasma membrane monoamine transporter	Inhibition	4.57	0.7%	Q7RTT9
	Plasmodium falciparum purine nucleoside phosphorylase		6.86
KCNK18	K2P18.1			0.1%	Q7Z418
KCNB2	Kv2.2		4.9	0%	Q92953
TAS2R14	TAS2R14	Agonist		0.1%	Q9NYV8
TAS2R40	TAS2R40	Agonist		0.1%	P59535
	VRAC

Broader ChEMBL bioactivity targets: 20 (assay-derived). Sample: Solute carrier family 22 member 2, Solute carrier family 22 member 2, Solute carrier organic anion transporter family member 1A1, Solute carrier organic anion transporter family member 1A4, Alpha-2A adrenergic receptor, Solute carrier family 22 member 2, Solute carrier family 22 member 1, Solute carrier family 22 member 1, Sodium channel alpha subunits; brain (Types I, II, III), Sodium-dependent serotonin transporter.

Bioactivity

ChEMBL activities: 20 potent at pChembl ≥ 5 of 38 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP2D6	8	IC50	10	nM	CHEMBL_ACT_18899401
P10634	7.03	IC50	94	nM	CHEMBL_ACT_672467
O08966	6.55	IC50	280	nM	CHEMBL_ACT_11000853
CYP2D6	6.21	IC50	610	nM	CHEMBL_ACT_672470
Q63089	6.05	IC50	900	nM	CHEMBL_ACT_11000895
Q63089	6.03	Ki	930	nM	CHEMBL_ACT_11002310
Q63089	5.96	IC50	1100	nM	CHEMBL_ACT_11000901
ABCB1	5.77	IC50	1700	nM	CHEMBL_ACT_19043899
Q64680	5.77	IC50	1700	nM	CHEMBL_ACT_672469
CYP2D6	5.75	IC50	1800	nM	CHEMBL_ACT_1701457
O70577	5.55	IC50	2800	nM	CHEMBL_ACT_11001327
SLC22A2	5.47	Ki	3400	nM	CHEMBL_ACT_11002860
O35913	5.42	Ki	3810	nM	CHEMBL_ACT_11002869
Q63089	5.39	IC50	4100	nM	CHEMBL_ACT_11001464
Q63089	5.37	Ki	4300	nM	CHEMBL_ACT_11003108
SCN1A	5.36	IC50	4400	nM	CHEMBL_ACT_375206
CYP2D6	5.34	Ki	4600	nM	CHEMBL_ACT_401507
ADRA2A	5.26	AC50	5452	nM	CHEMBL_ACT_25156471
CYP2D6	5.26	Ki	5500	nM	CHEMBL_ACT_401508
OPRM1	5.08	AC50	8376	nM	CHEMBL_ACT_25158217

Target pathways

Aggregated over 5 target gene(s): SLC29A4, KCNK18, KCNB2, TAS2R14, TAS2R40.

Top Reactome pathways

21 total, by targets touching each:

Pathway	Targets	Genes
Neuronal System	2	KCNB2, KCNK18
Potassium Channels	2	KCNB2, KCNK18
Signal Transduction	2	TAS2R14, TAS2R40
Signaling by GPCR	2	TAS2R14, TAS2R40
GPCR downstream signalling	2	TAS2R14, TAS2R40
G alpha (i) signalling events	2	TAS2R14, TAS2R40
Class C/3 (Metabotropic glutamate/pheromone receptors)	2	TAS2R14, TAS2R40
GPCR ligand binding	2	TAS2R14, TAS2R40
Sensory Perception	2	TAS2R14, TAS2R40
Sensory perception of taste	2	TAS2R14, TAS2R40
Sensory perception of sweet, bitter, and umami (glutamate) taste	2	TAS2R14, TAS2R40
Voltage gated Potassium channels	1	KCNB2
Tandem pore domain potassium channels	1	KCNK18
TWIK-related spinal cord K+ channel (TRESK)	1	KCNK18
Transport of small molecules	1	SLC29A4
Muscle contraction	1	KCNK18
Transport of vitamins, nucleosides, and related molecules	1	SLC29A4
SLC-mediated transmembrane transport	1	SLC29A4
Phase 4 - resting membrane potential	1	KCNK18
Cardiac conduction	1	KCNK18
Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane	1	SLC29A4

Dominant GO biological processes

GO term	Targets
potassium ion transport	2
potassium ion transmembrane transport	2
monoatomic ion transport	2
monoatomic ion transmembrane transport	2
detection of chemical stimulus involved in sensory perception of bitter taste	2
G protein-coupled receptor signaling pathway	2
signal transduction	2
sensory perception of taste	2
histamine metabolic process	1
neurotransmitter transport	1
obsolete serotonin transport	1
obsolete organic cation transport	1
obsolete monoamine transport	1
obsolete dopamine transport	1
obsolete norepinephrine transport	1

Indications & clinical

Indications

5 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
malaria	4	MONDO:0005136	EFO:0001068
Plasmodium falciparum malaria	3	MONDO:0005920	EFO:0007444
inborn error of immunity	2	MONDO:0003778	HP:0002721
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096

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
PHASE4	5
PHASE3	5
PHASE2	5
PHASE1	5
Not specified	4

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00451139	PHASE4	COMPLETED	Ototoxicity of Artemether / Lumefantrine (Coartem) and Other Antimalarials
NCT00495508	PHASE4	COMPLETED	Quinine vs. Artemether/Lumefantrine in Uncomplicated Malaria During Pregnancy
NCT00540202	PHASE4	UNKNOWN	Effectiveness of Oral Quinine and Artemether-Lumefantrine in the Treatment of Uncomplicated Malaria in Ugandan Children
NCT01805232	PHASE4	UNKNOWN	Intravenous Artesunate and Malaria
NCT02092766	PHASE4	COMPLETED	Parenteral Artesunate Compared to Quinine as a Cause of Late Anaemia in African Children With Malaria
NCT00124267	PHASE3	UNKNOWN	Efficacy of Intrarectal Versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria
NCT01258049	PHASE3	COMPLETED	Superiority of ArTiMist Versus Quinine in Children With Severe Malaria
NCT01374581	PHASE3	COMPLETED	Impact of Artemisinin-based Combination Therapy and Quinine on Treatment Failure and Resistance in Uncomplicated Malaria
NCT02563704	PHASE3	COMPLETED	A Trial of the Efficacy of Artesunate and Three Quinine Regimens in the Treatment of Severe Malaria in Children at the Ebolowa Regional Hospital - Cameroon
NCT02974348	PHASE3	COMPLETED	Antimalaria Drugs Susceptibility Testing for an Effective Management of Infected Patients in Sub-Sahara Africa
NCT07572396	PHASE2	RECRUITING	Phase II Study of Dysplasix™ Intravaginal Suppositories in Patients Patients With High-Risk HPV and Mild Cervical Cytologic Abnormalities
NCT00299208	PHASE2	COMPLETED	Azithromycin Combination Therapy for Malaria
NCT01047436	PHASE2	COMPLETED	Efficacy of ArTiMist™ in Children
NCT02276989	PHASE2	WITHDRAWN	Evaluation of a Compliance Marker in Prescription Opioid Abusers With Chronic Pain
NCT02492178	PHASE2	COMPLETED	Bio-availability of Rectal Artesunate in Children With Severe Falciparum Malaria
NCT00726895	PHASE1	COMPLETED	A Dose Proportionality Study of Quinine Sulfate Capsules Under Fasting Conditions
NCT00727272	PHASE1	COMPLETED	A Relative Bioavailability Study of Quinine Sulfate Capsules Under Fasting and Fed Conditions
NCT00779259	PHASE1	COMPLETED	Drug - Drug Interaction Study Between Quinine Sulfate and Theophylline
NCT00785980	PHASE1	COMPLETED	Drug - Drug Interaction Study of Quinine Sulfate and Ciprofloxacin
NCT01851473	PHASE1	COMPLETED	Interactions Between Intravenous Cocaine and Acetazolamide or Quinine
NCT02902198	Not specified	RECRUITING	Taste Physiology in Obese Volunteers Before and After Bariatric Surgery
NCT03565133	Not specified	COMPLETED	Quinine and Food Intake
NCT05682339	Not specified	COMPLETED	Effects of Intragastric Quinine, Alone or Combined With L-isoleucine, on Postprandial Glycaemic Control
NCT05720390	Not specified	COMPLETED	Effects of Intragastric Quinine, Alone or Combined With L-leucine, on Postprandial Glycaemic Control

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.

14 molecules share ≥1 primary target. Top 14 by shared-target count:

Molecule	Source	Status	Shared targets
ISOPROTERENOL	ChEMBL	Phase 4 (approved)	TAS2R14, TAS2R40
FLUFENAMIC ACID	ChEMBL	Phase 2	TAS2R14
Amantadine	PubChem	Approved	SLC29A4
Cimetidine	PubChem	Approved	SLC29A4
dalfampridine	PubChem	Approved	KCNB2
Desipramine	PubChem	Approved	SLC29A4
Dipyridamole	PubChem	Approved	SLC29A4
Fluoxetine	PubChem	Approved	SLC29A4
Histamine	PubChem	Approved	SLC29A4
Lidocaine	PubChem	Approved	KCNK18
Metformin	PubChem	Approved	SLC29A4
Nicotine	PubChem	Approved	SLC29A4
Quinidine	PubChem	Approved	SLC29A4
Verapamil	PubChem	Approved	SLC29A4