Hydroxychloroquine

Summary

Hydroxychloroquine (CHEMBL1535) is an approved small-molecule antirheumatic drug (ATC P01BA02) targeting TLR7 and TLR9; indicated across 83 conditions including malaria and pulmonary sarcoidosis; with CIViC clinical evidence for 1 variant-indication association (e.g. KRAS G12D in colorectal cancer).

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: P01BA02
• Targets: 2 (TLR7, TLR9)
• Indications: 83 conditions
• Clinical trials: 389
• Precision-oncology evidence (CIViC): 1 variant–indication association
• Chemistry: 335.9 Da · C18H26ClN3O

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1535
Name	Hydroxychloroquine
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	3652
ChEBI	CHEBI:5801
ATC	P01BA02
Molecular formula	C18H26ClN3O
Molecular weight	335.9
InChIKey	XXSMGPRMXLTPCZ-UHFFFAOYSA-N

SMILES: CCN(CCCC(C)NC1=C2C=CC(=CC2=NC=C1)Cl)CCO

IUPAC name: 2-[4-[(7-chloroquinolin-4-yl)amino]pentyl-ethylamino]ethanol

ChEBI definition: An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions.

Pharmacological roles (ChEBI): antimalarial, antirheumatic drug, dermatologic drug, anticoronaviral agent.

Also known as: Hidroxicloroquina, Hydroxychloroquine, Polirreumin, SID29215442, hydroxychloroquine, HYDROXYCHLOROQUINE, Hydroxycholoroquine, HYDROXYCHLOROQUINE SULFATE

Parent form; salt/anhydrous children: CHEMBL1690

Patent coverage: 11,338 distinct patent families (42,638 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 41,893 (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
TLR7	TLR7	Antagonist	5.56	0.2%	Q9NYK1
TLR9	TLR9	Antagonist	7.1	0.2%	Q9NR96

Broader ChEMBL bioactivity targets: 17 (assay-derived). Sample: Prelamin-A/C, Muscarinic acetylcholine receptor M4, Alpha-2A adrenergic receptor, Alpha-2C adrenergic receptor, Alpha-2B adrenergic receptor, Muscarinic acetylcholine receptor M5, Muscarinic acetylcholine receptor M2, Muscarinic acetylcholine receptor M1, Alpha-1D adrenergic receptor, Voltage-gated inwardly rectifying potassium channel KCNH2.

Bioactivity

ChEMBL activities: 17 potent at pChembl ≥ 5 of 23 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
TLR9	6.96	IC50	110	nM	CHEMBL_ACT_18776429
SIGMAR1	6.9	Ki	125.9	nM	CHEMBL_ACT_18838823
ACE2	6.14	IC50	720	nM	CHEMBL_ACT_24992607
TLR7	6.1	IC50	800	nM	CHEMBL_ACT_18776436
TLR7	6.1	IC50	800	nM	CHEMBL_ACT_23171447
TMEM97	6	Ki	1000	nM	CHEMBL_ACT_18838824
CHRM2	5.98	Ki	1049	nM	CHEMBL_ACT_7651680
ADRA1D	5.63	Ki	2346	nM	CHEMBL_ACT_7649512
KCNH2	5.6	Ki	2512	nM	CHEMBL_ACT_18838822
CHRM2	5.53	IC50	2951	nM	CHEMBL_ACT_7651679
CHRM3	5.32	Ki	4786	nM	CHEMBL_ACT_18838819
ADRA1D	5.32	IC50	4772	nM	CHEMBL_ACT_7649511
CHRM2	5.29	Ki	5129	nM	CHEMBL_ACT_18838818
CHRM4	5.26	Ki	5495	nM	CHEMBL_ACT_18838820
ADRA2A	5.19	Ki	6457	nM	CHEMBL_ACT_18838814
KCNH2	5.13	AC50	7400	nM	CHEMBL_ACT_25118331
TLR7	5.07	IC50	8600	nM	CHEMBL_ACT_19269539

Target pathways

Aggregated over 2 target gene(s): TLR7, TLR9.

Top Reactome pathways

13 total, by targets touching each:

Pathway	Targets	Genes
Trafficking and processing of endosomal TLR	2	TLR7, TLR9
Potential therapeutics for SARS	2	TLR7, TLR9
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling	2	TLR7, TLR9
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation	2	TLR7, TLR9
MyD88 dependent cascade initiated on endosome	2	TLR7, TLR9
PI3K Cascade	1	TLR9
Toll Like Receptor 9 (TLR9) Cascade	1	TLR9
Toll Like Receptor 7/8 (TLR7/8) Cascade	1	TLR7
Regulation of TLR by endogenous ligand	1	TLR7
SARS-CoV-1 activates/modulates innate immune responses	1	TLR7
SARS-CoV-2 activates/modulates innate and adaptive immune responses	1	TLR7
Defective regulation of TLR7 by endogenous ligand	1	TLR7
RSV-host interactions	1	TLR7

Dominant GO biological processes

GO term	Targets
toll-like receptor signaling pathway	2
inflammatory response	2
canonical NF-kappaB signal transduction	2
positive regulation of chemokine production	2
positive regulation of interferon-alpha production	2
positive regulation of interferon-beta production	2
positive regulation of type II interferon production	2
positive regulation of interleukin-6 production	2
positive regulation of interleukin-8 production	2
positive regulation of canonical NF-kappaB signal transduction	2
innate immune response	2
positive regulation of transcription by RNA polymerase II	2
positive regulation of inflammatory response	2
defense response to virus	2
immune system process	2

Indications & clinical

Indications

83 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
pulmonary sarcoidosis	3	MONDO:0001708	DOID:13406
rheumatoid arthritis	3	MONDO:0008383	EFO:0000685
Sjogren syndrome	3	MONDO:0010030	EFO:0000699
antiphospholipid syndrome	3	MONDO:8000010	EFO:0002689
habitual spontaneous abortion	3	MONDO:0006774	EFO:1000954
temporal arteritis	3	MONDO:0008538	EFO:1001209
thrombocytopenia	3	MONDO:0002049	HP:0001873
severe acute respiratory syndrome	3	MONDO:0005091	EFO:0000694
pneumonia	3	MONDO:0005249	EFO:0003106
cutaneous lupus erythematosus	3	MONDO:0005282	EFO:0003834
pneumocystosis	3	MONDO:0019121	EFO:0007448
viral pneumonia	3	MONDO:0006012	EFO:0007541
respiratory failure	3	MONDO:0021113	EFO:0009686
acute respiratory distress syndrome	3	MONDO:0006502	EFO:1000637
graft versus host disease	3	MONDO:0013730	MONDO:0013730
adult acute respiratory distress syndrome	3	MONDO:0100130	MONDO:0100130
preeclampsia	3	MONDO:0005081	EFO:0000668
influenza	3	MONDO:0005812	EFO:0007328
osteoarthritis	3	MONDO:0005178	MONDO:0005178
pericarditis	3	MONDO:0005904	EFO:0007427
systemic lupus erythematosus	3	MONDO:0007915	MONDO:0007915
B-cell chronic lymphocytic leukemia	2	MONDO:0004948	EFO:0000095
hepatocellular carcinoma	2	MONDO:0007256	EFO:0000182
Crohn disease	2	MONDO:0005011	EFO:0000384
glioblastoma	2	MONDO:0018177	EFO:0000519
leukemia	2	MONDO:0005059	EFO:0000565
neoplasm	2	MONDO:0005070	EFO:0000616
sarcoma	2	MONDO:0005089	EFO:0000691
small cell lung carcinoma	2	MONDO:0008433	EFO:0000702
HIV infectious disease	2	MONDO:0005109	EFO:0000764
exocrine pancreatic carcinoma	2	MONDO:0005192	EFO:0002618
non-small cell lung carcinoma	2	MONDO:0005233	EFO:0003060
chronic progressive multiple sclerosis	2	MONDO:0005284	EFO:0003840
osteoarthritis, knee	2	MONDO:0005416	EFO:0004616
lichen planus	2	MONDO:0006572	EFO:1000726
Zellweger spectrum disorders	2	MONDO:0019609	Orphanet:912
breast neoplasm	2	MONDO:0021100	MONDO:0007254
lung neoplasm	2	MONDO:0021117	MONDO:0008903
cholangiocarcinoma	2	MONDO:0019087	EFO:0005221
colorectal neoplasm	2	MONDO:0005335	EFO:0004142
mastocytosis	2	MONDO:0007950	EFO:0009001
type 1 diabetes mellitus	2	MONDO:0005147	MONDO:0005147
type 2 diabetes mellitus	2	MONDO:0005148	MONDO:0005148
porphyria cutanea tarda	2	MONDO:0015104	MONDO:0015104
viral infectious disease	2	MONDO:0005108	EFO:0000763
biliary tract neoplasm	2	MONDO:0005304	EFO:0003891
IgA glomerulonephritis	2	MONDO:0005342	EFO:0004194
hearing loss disorder	2	MONDO:0005365	EFO:0004238
infectious disease	2	MONDO:0005550	EFO:0005741
acute myeloid leukemia	1	MONDO:0018874	EFO:0000222
adenocarcinoma	1	MONDO:0004970	EFO:0000228
clear cell renal carcinoma	1	MONDO:0005005	EFO:0000349
cutaneous melanoma	1	MONDO:0005012	EFO:0000389
renal cell carcinoma	1	MONDO:0005086	EFO:0000681
melanoma	1	MONDO:0005105	EFO:0000756
plasma cell myeloma	1	MONDO:0009693	EFO:0001378
hepatitis C virus infection	1	MONDO:0005231	EFO:0003047
chronic hepatitis C virus infection	1	MONDO:0005354	EFO:0004220
hidradenitis suppurativa	1	MONDO:0006559	EFO:1000710
myelodysplastic syndrome	1	MONDO:0018881	EFO:0000198
osteosarcoma	1	MONDO:0009807	EFO:0000637
central nervous system neoplasm	1	MONDO:0006130	EFO:1000158
ovarian cancer	1	MONDO:0008170	MONDO:0008170
glioma	1	MONDO:0021042	MONDO:0100342
ulcerative colitis	1	MONDO:0005101	EFO:0000729
cystic fibrosis	1	MONDO:0009061	MONDO:0009061
lymphangioleiomyomatosis	1	MONDO:0011705	MONDO:0011705
retinitis pigmentosa	1	MONDO:0019200	MONDO:0019200
plasma cell neoplasm	1	MONDO:0004959	EFO:0000200
prostate carcinoma	0	MONDO:0005159	EFO:0001663
interstitial lung disease	0	MONDO:0015925	EFO:0004244

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

Clinical trials

Total trials: 389.

Phase distribution

Phase	Trials
PHASE2	106
PHASE3	80
Not specified	55
PHASE4	50
PHASE1/PHASE2	34
PHASE1	34
PHASE2/PHASE3	20
EARLY_PHASE1	10

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04981145	PHASE4	RECRUITING	The Efficacy and Safety of Iguratimod (IGU) in the Treatment of Primary Sjögren’s Syndrome
NCT05126147	PHASE4	RECRUITING	Hydroxychloroquine in Mild Graves’ Orbitopathy
NCT05626348	PHASE4	RECRUITING	The Clinical Efficacy of Immunomodulators in RA Patients
NCT05841758	PHASE4	RECRUITING	Hydroxychloroquine as a Steroid-sparing Agent in Extrapulmonary Sarcoidosis
NCT06676384	PHASE4	RECRUITING	Which of the Commonly Available and Approved Drugs in Addition to Standard of Care Can Significantly Improve the Slope of Estimated Glomerular Filtration Rate at Two Years When Compared to Standard of Care Alone in South-Asian Kidney Biopsy-proven Adult (≥18 Years) Primary IgA Nephropathy?
NCT07352566	PHASE4	NOT_YET_RECRUITING	Utilization of a Microdevice for Psoriasis and Atopic Dermatitis
NCT00176982	PHASE4	COMPLETED	Plaquenil for Alopecia Areata, Alopecia Totalis
NCT00259610	PHASE4	COMPLETED	Treatment of Early Aggressive Rheumatoid Arthritis (TEAR)
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT01207739	PHASE4	COMPLETED	Persistent Lyme Empiric Antibiotic Study Europe
NCT01326533	PHASE4	COMPLETED	Reducing Risk of Type 2 Diabetes: Hydroxychloroquine Use in Pre-Diabetes
NCT02351752	PHASE4	COMPLETED	Hydroxychloroquine Sulfate for Reduction of Proteinuria in Patients With IgA Nephropathy: a Self- Controlled Study
NCT02374021	PHASE4	COMPLETED	Treatments Against RA and Effect on FDG-PET/CT
NCT02433184	PHASE4	COMPLETED	Very Early Versus Delayed Etanercept in Patients With RA
NCT02451748	PHASE4	COMPLETED	IL-7 and IL-7R Expression in RA Patients With Active vs. Inactive Disease Treated With DMARD or CIMZIA
NCT02644499	PHASE4	COMPLETED	Comparison of Combination Disease Modifying Antirheumatic Drugs With Methotrexate Therapy in Early Rheumatoid Arthritis
NCT02648464	PHASE4	COMPLETED	Hydroxychloroquine for the Prevention of Cardiovascular Events in Myocardial Infarction Patients - a Safety Pilot Trial
NCT02765594	PHASE4	UNKNOWN	Hydroxychloroquine Sulfate Alleviates Persistent Proteinuria in IgA Nephropathy
NCT02874287	PHASE4	COMPLETED	Efficacy Study of Hydroxychloroquine to Treat High-risk Coronary Artery Disease.
NCT03025087	PHASE4	TERMINATED	Hydroxychloroquine and Cognitive Function After Surgery
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03229746	PHASE4	COMPLETED	Reposition of Second Line Treatment in Chronic Immune Thrombocytopenia
NCT03449758	PHASE4	COMPLETED	Effect of Sarilumab on Patient-reported Outcomes in Patients With Active Rheumatoid Arthritis
NCT03813771	PHASE4	UNKNOWN	Targeted Treatment Early With Etanercept + Methotrexate vs.T2T Care for DMARD-naïve Early RA Patients Based on naïve T-cell Stratification
NCT04077957	PHASE4	UNKNOWN	Treat-to-target Strategy in Ankylosing Spondylitis Using Etanercept and Conventional Synthetic DMARDs
NCT04161339	PHASE4	UNKNOWN	Anti-Inflammatory Drug and Endothelial Function
NCT04316377	PHASE4	UNKNOWN	Norwegian Coronavirus Disease 2019 Study
NCT04316494	PHASE4	TERMINATED	Hydroxychloroquine in ANCA Vasculitis Evaluation
NCT04330495	PHASE4	WITHDRAWN	Randomized, Controlled, Double-blind Clinical Trial Comparing the Efficacy and Safety of Chemoprophylaxis With Hydroxychloroquine in Patients Under Biological Treatment and / or JAK Inhibitors in the Prevention of SARS-CoV-2 Infection
NCT04334967	PHASE4	SUSPENDED	Hydroxychloroquine in Patients With Newly Diagnosed COVID-19 Compared to Standard of Care
NCT04338906	PHASE4	WITHDRAWN	Combination Therapy With Camostat Mesilate + Hydroxychloroquine for COVID-19
NCT04341493	PHASE4	TERMINATED	Hydroxychloroquine vs Nitazoxanide in Patients With COVID-19
NCT04346667	PHASE4	TERMINATED	Post-Exposure Prophylaxis for Asymptomatic SARS-CoV-2 COVID-19 Patients With choloroquinE Compounds
NCT04351191	PHASE4	TERMINATED	PRophylaxis of Exposed COVID-19 Individuals With Mild Symptoms Using choloroquinE Compounds
NCT04351919	PHASE4	WITHDRAWN	Assessment of Efficacy and Safety of HCQ and Antibiotics Administrated to Patients COVID19(+)
NCT04359316	PHASE4	UNKNOWN	Azithromycin in Hospitalized COVID-19 Patients
NCT04359615	PHASE4	UNKNOWN	Favipiravir in Hospitalized COVID-19 Patients
NCT04362332	PHASE4	TERMINATED	Chloroquine, Hydroxychloroquine or Only Supportive Care in Patients AdmItted With Moderate to Severe COVID-19
NCT04370782	PHASE4	COMPLETED	Hydroxychloroquine and Zinc With Either Azithromycin or Doxycycline for Treatment of COVID-19 in Outpatient Setting
NCT04382625	PHASE4	WITHDRAWN	Hydroxychloroquine in SARS-CoV-2 (COVID-19) Pneumonia Trial

Clinical evidence (CIViC)

Variant × indication × effect (1 predictive associations from 1 curated evidence items):

Variant	Indication	Effect	Therapy	Level	CIViC
KRAS G12D	Colorectal Cancer	Sensitivity/Response	Binimetinib + Bevacizumab + Hydroxychloroquine	CIViC C	EID10797

Pharmacology

Pharmacogenomics

PharmGKB dosing guidelines (1) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):

Guideline	Source	Gene(s)	Dosing	Recommendation
Annotation of CPIC Guideline for aminosalicylic acid, chloramphenicol,	CPIC	G6PD

PharmGKB also curates 1 clinical and 31 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.

10 molecules share ≥1 primary target. Top 10 by shared-target count:

Molecule	Source	Status	Shared targets
AFIMETORAN	ChEMBL	Phase 2	TLR7, TLR9
MHV-370	ChEMBL	Phase 2	TLR7, TLR9
IMIQUIMOD	ChEMBL	Phase 4 (approved)	TLR7
CURCUMIN	ChEMBL	Phase 3	TLR9
THIMEROSAL	ChEMBL	Phase 3	TLR9
CPG-52852	ChEMBL	Phase 2	TLR7
GSK-2245035	ChEMBL	Phase 2	TLR7
RESIQUIMOD	ChEMBL	Phase 2	TLR7
VESATOLIMOD	ChEMBL	Phase 2	TLR7
Chloroquine	PubChem	Approved	TLR9