Proguanil
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Also known as ChlorguanideChloroguanideSID11112433SID174006624NACHLOROGUANIDE HYDROCHLORIDE
Summary
Proguanil (CHEMBL1377) is an approved small-molecule antiprotozoal drug (ATC P01BB01); indicated across 4 conditions including malaria and plasmodium falciparum malaria.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: P01BB01 (+1 more)
- Indications: 4 conditions
- Clinical trials: 13
- Chemistry: 253.73 Da · C11H16ClN5
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL1377 |
| Name | Proguanil |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 6178111 |
| ChEBI | CHEBI:8455 |
| ATC | P01BB01, P01BB51 |
| Molecular formula | C11H16ClN5 |
| Molecular weight | 253.73 |
| InChIKey | SSOLNOMRVKKSON-UHFFFAOYSA-N |
SMILES: CC(C)N=C(N)/N=C(\N)/NC1=CC=C(C=C1)Cl
IUPAC name: (1E)-1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine
ChEBI definition: A biguanide compound which has isopropyl and p-chlorophenyl substituents on the terminal N atoms. A prophylactic antimalarial drug, it works by inhibiting the enzyme dihydrofolate reductase, which is involved in the reproduction of the malaria parasites Plasmodium falciparum and P. vivax within the red blood cells.
Pharmacological roles (ChEBI): antimalarial, antiprotozoal drug, EC 1.5.1.3 (dihydrofolate reductase) inhibitor.
Also known as: Chlorguanide, Chloroguanide, Proguanil, SID11112433, PROGUANIL, SID174006624, NA, CHLOROGUANIDE HYDROCHLORIDE, proguanil
Parent form; salt/anhydrous children: CHEMBL1201059
Patent coverage: 6,003 distinct patent families (21,481 SureChEMBL compound mentions), from 5 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
Broader ChEMBL bioactivity targets: 10 (assay-derived). Sample: Prelamin-A/C, Alpha-2A adrenergic receptor, D(1A) dopamine receptor, Sodium-dependent noradrenaline transporter, Sodium-dependent serotonin transporter, Sodium-dependent dopamine transporter, Voltage-gated inwardly rectifying potassium channel KCNH2, Cytochrome P450 2D6, Cytochrome P450 1A2, Trace amine-associated receptor 1.
Bioactivity
ChEMBL activities: 7 potent at pChembl ≥ 5 of 11 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| SLC6A2 | 5.97 | AC50 | 1067 | nM | CHEMBL_ACT_25145840 |
| LMNA | 5.7 | Potency | 1995 | nM | CHEMBL_ACT_3643722 |
| Q923Y8 | 5.27 | EC50 | 5400 | nM | CHEMBL_ACT_17951920 |
| CYP1A2 | 5.1 | AC50 | 7943 | nM | CHEMBL_ACT_6064165 |
| DRD1 | 5.08 | AC50 | 8264 | nM | CHEMBL_ACT_25115050 |
| CYP2D6 | 5 | Potency | 10000 | nM | CHEMBL_ACT_4998212 |
| CYP2D6 | 5 | AC50 | 10000 | nM | CHEMBL_ACT_6071637 |
Target pathways
No target-pathway data for this drug (no mapped target genes).
Indications & clinical
Indications
4 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 |
| gastroesophageal reflux disease | 1 | MONDO:0007186 | EFO:0003948 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 13.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 4 |
| PHASE1 | 3 |
| Not specified | 3 |
| PHASE2/PHASE3 | 1 |
| PHASE2 | 1 |
| PHASE1/PHASE2 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00421473 | PHASE4 | COMPLETED | Drug Interaction Study Between Atovaquone and Antiretroviral Agents in HIV-1 Infected Patients |
| NCT00451139 | PHASE4 | COMPLETED | Ototoxicity of Artemether / Lumefantrine (Coartem) and Other Antimalarials |
| NCT02564471 | PHASE4 | COMPLETED | Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis. |
| NCT03178643 | PHASE4 | COMPLETED | Enhancing Preventive Therapy of Malaria In Children With Sickle Cell Anemia in East Africa (EPiTOMISE) |
| NCT00084227 | PHASE2/PHASE3 | COMPLETED | Azithromycin Plus Chloroquine Versus Atovaquone-Proguanil For The Treatment Of Uncomplicated Plasmodium Falciparum Malaria In South America |
| NCT00984256 | PHASE2 | COMPLETED | Weekly Dosing of Malarone ® for Prevention of Malaria |
| NCT01319448 | PHASE1/PHASE2 | COMPLETED | Intermittent Preventive Treatment for Malaria in Patient With Sickle Cell Disease |
| NCT01456546 | PHASE1 | COMPLETED | Impact of CYP2C19*17 on the Pharmacokinetics of Proguanil and Clopidogrel |
| NCT04568772 | PHASE1 | COMPLETED | Study to Evaluate the Influence of Tegoprazan on the Pharmacokinetics of Proguanil in Healthy Volunteers |
| NCT06294912 | PHASE1 | COMPLETED | A Study to Evaluate Antimalarial Activity and Safety of MK-7602 in Healthy Adults (MK-7602-003) |
| NCT02080026 | Not specified | COMPLETED | Target Antigens Induced by Plasmodium Falciparum Sporozoite Immunization Under Chemoprophylaxis |
| NCT02098590 | Not specified | COMPLETED | Chemoprophylaxis and Plasmodium Falciparum NF54 Sporozoite Immunization Challenged by Heterologous Infection |
| NCT03454048 | Not specified | COMPLETED | Controlled Human Malaria Infection Model for Evaluation of Transmission-blocking Interventions - Study 2 |
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 10 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).
Related Atlas pages
- Diseases: malaria, Plasmodium falciparum malaria