Drug Information

Drug (ID: DG01155) and It's Reported Resistant Information

• Name: Proguanil
• Synonyms: Proguanil; Chloroguanide; Chlorguanide; Chlorguanid; Paludrin; Bigumal; 500-92-5; Proguanilum; 1-(p-Chlorophenyl)-5-isopropylbiguanide; Paludrine; N1-p-Chlorophenyl-N5-isopropylbiguanide; 1-Isopropyl-5-(4-chlorophenyl)biguanide; UNII-S61K3P7B2V; CHEBI:8455; N-(4-Chlorophenyl)-N'-(isopropyl)-imidodicarbonimidic diamide; Imidodicarbonimidic diamide, N-(4-chlorophenyl)-N'-(1-methylethyl)-; N1-(4-Chlorophenyl)-N5-isopropylbiguanide; S61K3P7B2V; BIGUANIDE, 1-(p-CHLOROPHENYL)-5-ISOPROPYL-; Proguanile [DCIT]; Proguanile; N-(4-chlorophenyl)-N'-(propan-2-yl)imidodicarbonimidic diamide; N-(4-Chlorophenyl)-N'-(1-methylethyl)imidodicarbonimidic diamide; Proguanil [INN:BAN]; RP-3359; Proguanilum [INN-Latin]; (hydrochloride); Tirian (hydrochloride); Palusil (hydrochloride); Diguanyl (hydrochloride); Drinupal (hydrochloride); NCGC00016528-01; CAS-637-32-1; Paludrine (hydrochloride); EINECS 207-915-6; M-4888 (hydrochloride); BRN 2811599; SN-12837 (hydrochloride); MFCD00866201; Proguanil (INN); NSC12977; Spectrum_001588; SpecPlus_000667; Prestwick0_000999; Prestwick1_000999; Prestwick2_000999; Prestwick3_000999; Spectrum2_001135; Spectrum3_001659; Spectrum4_000622; Spectrum5_001384; CHEMBL1377; SCHEMBL45726; BSPBio_001097; BSPBio_003417; KBioGR_001204; KBioSS_002068; 4-12-00-01198 (Beilstein Handbook Reference); BIDD:GT0576; DivK1c_006763; SPBio_001029; SPBio_002988; BPBio1_001207; DTXSID3022794; SCHEMBL16894670; SCHEMBL17300525; KBio1_001707; KBio2_002068; KBio2_004636; KBio2_007204; KBio3_002637; HY-B0806; (4-chlorphenyl)-5-isopropylbiguanid; BDBM50227829; s5927; CS-6234; DB01131; N'-4-chlorophenyl-n5-isopropylbiguanide; NCGC00016528-02; NCGC00016528-03; CS-12345; SBI-0052839.P002; AB00053776; V0783; C07631; D08428; AB00053776_05; A901482; BRD-K28183345-003-05-6; BRD-K28183345-003-07-2; 1-(4-Chlorophenyl)-3-(N-isopropylcarbamimidoyl)guanidine; 1-(4-chlorophenyl)-5-isopropylbiguanide;N1-(4-Chlorophenyl)-N5-isopropylbiguanide
• Indication:
  In total 1 Indication(s)
  Malaria [ICD-11: 1F45]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Falciparum malaria [ICD-11: 1F40]; [1]
• Target: Polypeptide deformylase (PDF); DEFM_HUMAN; [1]
• Formula: C11H16ClN5
• IsoSMILES: CC(C)N=C(N)/N=C(\\N)/NC1=CC=C(C=C1)Cl
• InChI: 1S/C11H16ClN5/c1-7(2)15-10(13)17-11(14)16-9-5-3-8(12)4-6-9/h3-7H,1-2H3,(H5,13,14,15,16,17)
• InChIKey: SSOLNOMRVKKSON-UHFFFAOYSA-N
• PubChem CID: 6178111
• ChEBI ID: CHEBI:8455
• TTD Drug ID: D0P8RS
• INTEDE ID: DR1347
• DrugBank ID: DB01131

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-01: Infectious/parasitic diseases

Falciparum malaria [ICD-11: 1F40]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Bifunctional dihydrofolate reductase-thymidylate synthase (PFDHFR) [1]

• Molecule Alteration: Missense mutation; p.N51I
• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Key Molecule: Bifunctional dihydrofolate reductase-thymidylate synthase (PFDHFR) [1]

• Molecule Alteration: Missense mutation; p.N51I
• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Key Molecule: Bifunctional dihydrofolate reductase-thymidylate synthase (PFDHFR) [1]

• Molecule Alteration: Missense mutation; p.C59R
• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

Key Molecule: Bifunctional dihydrofolate reductase-thymidylate synthase (PFDHFR) [1]

• Molecule Alteration: Missense mutation; p.S108N
• Resistant Disease: Falciparum malaria [ICD-11: 1F40.0]
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Sanger sequencing analysis
• Mechanism Description: Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples.

References

• Ref 1: Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile .Am J Trop Med Hyg. 2021 Mar 29;104(5):1811-1813. doi: 10.4269/ajtmh.20-1095. 10.4269/ajtmh.20-1095