Drug Information

Drug (ID: DG00058) and It's Reported Resistant Information

• Name: Amodiaquine
• Synonyms: Amodiachin; Amodiachinum; Amodiaquin; Amodiaquina; Amodiaquinum; Basoquin; CQA; Camochin; Camoquin; Camoquinal; Camoquine; Flavoquin; Flavoquine; Miaquin; Sunoquine; Amodiaquine hydrochloride; Amodiaquine USP24; SN 10751; AMODIAQUINE, FLAVOQUINE; Amodiaquina [INN-Spanish]; Amodiaquinum [INN-Latin]; CAM-AQ 1; CAM-AQI; Cam-AQ1; Camoquin (TN); Flavoquine (TN); SN 10,751; WR-002977; Amodiaquine (USAN/INN); Amodiaquine [USAN:INN:BAN]; Amodiaquine, ring-closed; S. N. 10751
• Indication:
  In total 1 Indication(s)
  Malaria [ICD-11: 1F45]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Astrocytoma [ICD-11: 2F36]; [1]
• Target: Histamine N-methyltransferase (HNMT); HNMT_HUMAN; [1]
• Formula: C20H22ClN3O
• IsoSMILES: CCN(CC)CC1=C(C=CC(=C1)NC2=C3C=CC(=CC3=NC=C2)Cl)O
• InChI: 1S/C20H22ClN3O/c1-3-24(4-2)13-14-11-16(6-8-20(14)25)23-18-9-10-22-19-12-15(21)5-7-17(18)19/h5-12,25H,3-4,13H2,1-2H3,(H,22,23)
• InChIKey: OVCDSSHSILBFBN-UHFFFAOYSA-N
• PubChem CID: 2165
• ChEBI ID: CHEBI:2674
• TTD Drug ID: D04NQI
• VARIDT ID: DR00976
• INTEDE ID: DR0102
• DrugBank ID: DB00613

Type(s) of Resistant Mechanism of This Drug

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Astrocytoma [ICD-11: 2F36]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Chloroquine resistance transporter (CRT) [1]

• Molecule Alteration: Missense mutation; p.K76T
• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium falciparum strains; 5833
• Experiment for Molecule Alteration: MIP probes and PCR sequencing assay
• Experiment for Drug Resistance: SYBR Green I detection assay
• Mechanism Description: Increasingly, molecular genetic markers for antimalarial drug resistance have been identified, an advance that facilitates the monitoring of the emergence and spread of resistance. Currently, reliable molecular markers are available for P. falciparum resistance to artemisinins (mutations in the propeller region of Pfkelch), sulfadoxine-pyrimethamine (mutations in the dihydrofolate reductase [PfDHFR] and dihydropteroate synthase [PfDHPS] genes), mefloquine (MQ) (amplification of the multidrug resistance-1 gene [PfMDR1]), and piperaquine (amplification of PfPlasmepsin2/3 and specific mutations in the P. falciparum chloroquine resistance transporter gene.

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Molecule Alteration: Missense mutation; p.N86Y
• Resistant Disease: Malaria [ICD-11: 1F45.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium falciparum strains; 5833
• Experiment for Molecule Alteration: MIP probes and PCR sequencing assay
• Experiment for Drug Resistance: SYBR Green I detection assay
• Mechanism Description: Increasingly, molecular genetic markers for antimalarial drug resistance have been identified, an advance that facilitates the monitoring of the emergence and spread of resistance. Currently, reliable molecular markers are available for P. falciparum resistance to artemisinins (mutations in the propeller region of Pfkelch), sulfadoxine-pyrimethamine (mutations in the dihydrofolate reductase [PfDHFR] and dihydropteroate synthase [PfDHPS] genes), mefloquine (MQ) (amplification of the multidrug resistance-1 gene [PfMDR1]), and piperaquine (amplification of PfPlasmepsin2/3 and specific mutations in the P. falciparum chloroquine resistance transporter gene.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Chloroquine resistance transporter (CRT) [2]

• Molecule Alteration: Missense mutation; p.C101F
• Sensitive Disease: Malaria [ICD-11: 1F45.0]
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vitro Model: Plasmodium falciparum asexual blood-stage parasites; 5833
• Experiment for Molecule Alteration: DNA clones asssay
• Experiment for Drug Resistance: SYBR Green I detection assay
• Mechanism Description: This mutation (C101F) also reversed Dd2-mediated CQ resistance, sensitized parasites to amodiaquine, quinine, and artemisinin, and conferred amantadine and blasticidin resistance.

References

• Ref 1: Evolution of Multidrug Resistance in Plasmodium falciparum: a Longitudinal Study of Genetic Resistance Markers in the Greater Mekong Subregion. Antimicrob Agents Chemother. 2021 Nov 17;65(12):e0112121. doi: 10.1128/AAC.01121-21. Epub 2021 Sep 13.
• Ref 2: A Variant PfCRT Isoform Can Contribute to Plasmodium falciparum Resistance to the First-Line Partner Drug Piperaquine. mBio. 2017 May 9;8(3):e00303-17. doi: 10.1128/mBio.00303-17.