Details of the Drug-Related molecule(s) Expression Atlas

General Information of Drug (ID: DMBL79I)

Drug Name

Proguanil Drug Info

Synonyms

Bigumal; Chlorguanid; Chlorguanide; Chloriguane; Chloroguanide; Paludrin; Proguanile; Proguanilum; Proguanile [DCIT]; Diguanyl (hydrochloride); Drinupal (hydrochloride); Paludrine (TN); Paludrine (hydrochloride); Palusil (hydrochloride); Proguanil [INN:BAN]; Proguanilum [INN-Latin]; RP-3359; Tirian (hydrochloride); M-4888 (hydrochloride); SN-12837 (hydrochloride); N1-p-Chlorophenyl-N5-isopropylbiguanide; N-(4-Chlorophenyl)-N'-(1-methylethyl)imidodicarbonimidic diamide; N-(4-Chlorophenyl)-N'-(isopropyl)-imidodicarbonimidic diamide; N-(4-chlorophenyl)-N'-(propan-2-yl)imidodicarbonimidic diamide; (1E)-1-[amino-(4-chloroanilino)methylidene]-2-propan-2-ylguanidine; 1-(p-Chlorophenyl)-5-isopropylbiguanide; 1-Isopropyl-5-(4-chlorophenyl)biguanide

Indication

Disease Entry	ICD 11	Status	REF
Malaria	1F40-1F45	Approved	[1]

Therapeutic Class

Antimalarials

Cross-matching ID

PubChem CID: 6178111
ChEBI ID: CHEBI:8455
CAS Number: CAS 500-92-5
TTD Drug ID: DMBL79I
INTEDE Drug ID: DR1347

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Polypeptide deformylase (PDF)	TT9SL3Q	DEFM_HUMAN	Inhibitor	[2]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Phase 4	[3]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Phase 4	[4]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Phase 4	[5]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Phase 4	[6]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Phase 4	[4]

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The Expression Level of Molecule(s) in Normal Tissue of Major ADME-Related Organs

Molecule	Molecule Type	Gene Name	Liver	Colon	Kidney	Small Intestine
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	12.054	3.968	2.945	4.1
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	10.036	5.779	6.508	6.481
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	11.76	5.931	6.164	9.423
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	11.692	6.58	4.984	9.089

Molecule Expression Atlas in Normal Tissue of Major ADME-related organs

The Expression Level of Molecule(s) between Disease Section and Healthy Individual Tissue

The Studied Disease

Malaria

ICD Disease Classification

1F40-1F45

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Polypeptide deformylase (PDF)	DTT	PDF	8.87E-16	-0.54	-0.86
Cytochrome P450 2E1 (CYP2E1)	DME	CYP2E1	1.94E-06	7.00E-02	4.44E-01
Cytochrome P450 1A2 (CYP1A2)	DME	CYP1A2	7.09E-03	2.84E-02	1.20E-01
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	6.34E-01	4.42E-03	2.22E-02
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	5.63E-01	-9.82E-03	-4.80E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	7.29E-03	-3.47E-02	-1.80E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Opportunities and challenges in antiparasitic drug discovery. Nat Rev Drug Discov. 2005 Sep;4(9):727-40.
2	Transformation with human dihydrofolate reductase renders malaria parasites insensitive to WR99210 but does not affect the intrinsic activity of proguanil. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10931-6.
3	In vitro proguanil activation to cycloguanil is mediated by CYP2C19 and CYP3A4 in adult Chinese liver microsomes. Acta Pharmacol Sin. 2000 Aug;21(8):747-52.
4	Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67.
5	Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448.
6	Polymorphic oxidative metabolism of proguanil in a Nigerian population. Eur J Clin Pharmacol. 2002 Nov;58(8):543-5.