proguanil 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
2282 500-92-5

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • proguanil
  • proguanil hydrochloride
  • chloroguanide
  • chloroguanide hydrochloride
  • proguanil HCl
  • chloroguanide HCl
A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.
  • Molecular weight: 253.73
  • Formula: C11H16ClN5
  • CLOGP: 2.53
  • LIPINSKI: 0
  • HAC: 5
  • HDO: 5
  • TPSA: 83.79
  • ALOGS: -3.34
  • ROTB: 2
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 9.09 mg/mL Benet LZ, Broccatelli F, Oprea TI
BA (Bioavailability) 60 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 0.020 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 2.958 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 5.105 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.524 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 13.760 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 40.390 % High 1
herg hERG pIC50 4.870 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 8.551 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 4.955 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 18.920 % High 1
kinase-safety-class ACVR2A,ACVR2B,AKT1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK1,CDK4,CDK5,CDK9,CHEK1,CSF1R,DDR1,DYRK1B,EIF2AK3,EPHA2,EPHB4,ERBB2,FLT3,GRK2,GSK3B,ITK,JAK1,JAK2,KIT,MAP2K6,MAP3K1,MAP3K21,MAP3K7,MAP4K1,MAP4K3,MAPK1,MAPK10,MAPK12,MAPK7,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PAK4,PDK2,PDK4,PDPK1,PIK3CB,PIK3CD,PIM2,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ULK2 65
kinase-selectivity-class EIF2AK3,GRK2,MAPK7,PDK4,STK33,TEK 6
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 1.919 High 1
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 2.576 High 1
mh-clint Mouse hepatocyte intrinsic clearance 11.940 High 1
mppb Mouse plasma protein binding (% unbound) 16.380 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.365 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 18.330 % High 1
rat-kpuu-brain Rat brain Kpuu 0.136 % High 1
rh-clint Rat hepatocyte intrinsic clearance 13.932 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 34.630 % High 1
rppb Rat plasma protein binding (% unbound) 21.320 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 748.170 uM High 1

Approvals:

DateAgencyCompanyOrphan
July 14, 2000 FDA GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malaria 113.48 38.96 15 1209 198 90627025
Schizophrenia 54.30 38.96 16 1208 14898 90612325
Psychotic disorder 50.11 38.96 18 1206 31212 90596011
Hypomania 43.42 38.96 12 1212 8885 90618338
Dermatitis acneiform 42.52 38.96 11 1213 6343 90620880

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malaria 92.24 30.92 13 769 205 42620348
Plasmodium falciparum infection 43.15 30.92 6 776 85 42620468
Hallucination 43.12 30.92 21 761 57486 42563067
Abnormal dreams 32.10 30.92 10 772 8261 42612292

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malaria 141.72 34.16 20 1585 407 110587287
Schizophrenia 51.11 34.16 17 1588 21809 110565885
Psychotic disorder 46.81 34.16 20 1585 50917 110536777
Hypomania 40.92 34.16 12 1593 10198 110577496
Plasmodium falciparum infection 40.58 34.16 6 1599 170 110587524
Total lung capacity increased 34.28 34.16 9 1596 5103 110582591
Dermatitis acneiform 34.20 34.16 11 1594 12684 110575010

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC P01BB01 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Biguanides
ATC P01BB51 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Biguanides
ATC P01BB52 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ANTIPROTOZOALS
ANTIMALARIALS
Biguanides
FDA MoA N0000000191 Dihydrofolate Reductase Inhibitors
FDA EPC N0000175482 Antimalarial
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000962 Antimalarials
MeSH PA D000963 Antimetabolites
MeSH PA D000977 Antiparasitic Agents
MeSH PA D000981 Antiprotozoal Agents
CHEBI has role CHEBI:35441 antiinfective agent
CHEBI has role CHEBI:35820 antiprotozoal drug
CHEBI has role CHEBI:38068 antimalarial
CHEBI has role CHEBI:50683 EC 1.5.1.3 (dihydrofolate reductase) inhibitor
CHEBI has role CHEBI:75835 anti-anaemic agent

Related Drugs by ATC class:

P01BB Biguanides 3 drugs
atovaquonechloroquinecycloguanil

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Falciparum malaria indication 62676009 DOID:14067
Chloroquine-Resistant Plasmodium Falciparum Malaria Prevention indication
Plasmodium Falciparum Malaria Prevention indication
Vivax malaria off-label use 27052006 DOID:12978
Acute nephropathy contraindication 58574008
Hepatic failure contraindication 59927004
Hyperglycemia contraindication 80394007 DOID:4195
Anemia due to enzyme deficiency contraindication 111577008
Disease of liver contraindication 235856003 DOID:409
Chronic diarrhea contraindication 236071009
Vomiting contraindication 422400008
Malabsorption States contraindication




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 11.73 Basic
pKa2 2.36 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme INHIBITOR DRUGBANK CHEMBL
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase Enzyme WOMBAT-PK
Trace amine-associated receptor 1 GPCR EC50 5.27 CHEMBL

External reference:

IDSource
4021225 VUID
N0000148669 NUI
D02487 KEGG_DRUG
637-32-1 SECONDARY_CAS_RN
4021225 VANDF
C0008241 UMLSCUI
CHEBI:8455 CHEBI
CHEMBL1377 ChEMBL_ID
CHEMBL1201059 ChEMBL_ID
DB01131 DRUGBANK_ID
D002727 MESH_DESCRIPTOR_UI
6178111 PUBCHEM_CID
9676 IUPHAR_LIGAND_ID
418 INN_ID
S61K3P7B2V UNII
142428 RXNORM
15669 MMSL
d04593 MMSL
002942 NDDF
002943 NDDF
16970001 SNOMEDCT_US
387094004 SNOMEDCT_US
395845004 SNOMEDCT_US
XEW PDB_CHEM_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
MALARONE HUMAN PRESCRIPTION DRUG LABEL 2 0173-0675 TABLET, FILM COATED 100 mg ORAL NDA 25 sections
MALARONE HUMAN PRESCRIPTION DRUG LABEL 2 0173-0676 TABLET, FILM COATED 25 mg ORAL NDA 25 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 0378-4160 TABLET, FILM COATED 25 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 0378-4162 TABLET, FILM COATED 100 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 10544-909 TABLET, FILM COATED 100 mg ORAL ANDA 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 33261-900 TABLET, FILM COATED 100 mg ORAL ANDA 22 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 42254-150 TABLET 100 mg ORAL ANDA 20 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 43063-393 TABLET, FILM COATED 100 mg ORAL ANDA 25 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 50090-2980 TABLET, FILM COATED 100 mg ORAL NDA authorized generic 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 51407-869 TABLET, FILM COATED 100 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 54868-6393 TABLET, FILM COATED 100 mg ORAL ANDA 22 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 63187-879 TABLET, FILM COATED 100 mg ORAL ANDA 26 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 63629-5531 TABLET, FILM COATED 100 mg ORAL NDA authorized generic 26 sections
Atovaquone and Proguanil HCl HUMAN PRESCRIPTION DRUG LABEL 2 66993-060 TABLET, FILM COATED 100 mg ORAL NDA authorized generic 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 68001-245 TABLET, FILM COATED 100 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 68071-3473 TABLET, FILM COATED 100 mg ORAL ANDA 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 68071-3488 TABLET, FILM COATED 100 mg ORAL ANDA 26 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 68258-1104 TABLET, FILM COATED 100 mg ORAL ANDA 22 sections
Atovaquone and Proguanil Hydrochloride Pediatric HUMAN PRESCRIPTION DRUG LABEL 2 68462-402 TABLET, FILM COATED 25 mg ORAL ANDA 27 sections
Atovaquone and Proguanil Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 2 68462-404 TABLET, FILM COATED 100 mg ORAL ANDA 27 sections