Drug Information

Drug (ID: DG00167) and It's Reported Resistant Information

Name	Pyronaridine
Synonyms	Malaridine; Pyronaridine phosphate salt; Benzonaphthyridine 7351; 2-Methoxy-7-chloro-10-(3',5'-bis(pyrrolin-1-ylmethyl)-4'-hydroxyphenylamino)benzo(b)-1,5-naphthyridine; 4-((7-Chloro-2-methoxybenzo(b)-1,5-naphthyridin-10-yl)amino)-2,6-bis(1-pyrrolidinylmethyl)phenol; 4-[(7-chloro-2-methoxy-1,5-dihydrobenzo[b][1,5]naphthyridin-10-yl)imino]-2,6-bis(pyrrolidin-1-ylmethyl)cyclohexa-2,5-dien-1-one; 4-[(7-chloro-2-methoxybenzo[b][1,5]naphthyridin-10-yl)amino]-2,6-bis(pyrrolidin-1-ylmethyl)phenol Click to Show/Hide
Indication	In total 1 Indication(s) Malaria [ICD-11: 1F45] Approved [1]
Structure
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	Sarcoplasmic/endoplasmic reticulum calcium ATPase (ATP2A)	NOUNIPROTAC	[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula	C29H32ClN5O2
IsoSMILES	COC1=NC2=C(C3=C(C=C(C=C3)Cl)N=C2C=C1)NC4=CC(=C(C(=C4)CN5CCCC5)O)CN6CCCC6
InChI	1S/C29H32ClN5O2/c1-37-26-9-8-24-28(33-26)27(23-7-6-21(30)16-25(23)32-24)31-22-14-19(17-34-10-2-3-11-34)29(36)20(15-22)18-35-12-4-5-13-35/h6-9,14-16,36H,2-5,10-13,17-18H2,1H3,(H,31,32)
InChIKey	DJUFPMUQJKWIJB-UHFFFAOYSA-N
PubChem CID	107771
ChEBI ID	CHEBI:135951
TTD Drug ID	D0E0KQ
DrugBank ID	DB12975

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

Click to Show/Hide the Resistance Disease of This Class

Astrocytoma [ICD-11: 2F36]

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Drug Resistance Data Categorized by Their Corresponding Mechanisms
Irregularity in Drug Uptake and Drug Efflux (IDUE)		Click to Show/Hide
Key Molecule: Chloroquine resistance transporter (CRT)			[1]
Molecule Alteration	Missense mutation	p.K76T	Molecule Info
Resistant Disease	Malaria [ICD-11: 1F45.0]		Disease Info
Experimental Note	Discovered Using In-vivo Testing Model
In Vitro Model	Plasmodium falciparum strains		5833
Experiment for Drug Resistance	[3H]-hypoxanthine assay
Mechanism Description	The pyronaridine IC50 (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the k76T mutation (p-value = 0.020). The reduced susceptibility to pyronaridine, defined as IC50 > 60 nM, was significantly associated with the k76T mutation (p-value = 0.004).

References

Ref 1	The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine. Parasit Vectors. 2016 Feb 9;9:77. doi: 10.1186/s13071-016-1358-z.