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

General Information of Drug (ID: DMX6OE3)

Drug Name

Dabrafenib Drug Info

Synonyms

1195765-45-7; Dabrafenib (GSK2118436); Tafinlar; GSK2118436A; UNII-QGP4HA4G1B; GSK 2118436; QGP4HA4G1B; N-(3-(5-(2-aminopyrimidin-4-yl)-2-tert-butylthiazol-4-yl)-2-fluorophenyl)-2,6-difluorobenzenesulfonamide; CHEBI:75045; N-[3-[5-(2-Amino-4-pyrimidinyl)-2-(tert-butyl)-4-thiazolyl]-2-fluorophenyl]-2,6-difluorobenzenesulfonamide; N-{3-[5-(2-aminopyrimidin-4-yl)-2-tert-butyl-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide; GSK-2118436A; Dabrafenib [USAN:INN]; GSK2118436

Indication

Disease Entry	ICD 11	Status	REF
Melanoma	2C30	Approved	[1]

Cross-matching ID

PubChem CID: 44462760
ChEBI ID: CHEBI:75045
CAS Number: CAS 1195765-45-7
TTD Drug ID: DMX6OE3
VARIDT Drug ID: DR00164
INTEDE Drug ID: DR0403
ACDINA Drug ID: D00163

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Serine/threonine-protein kinase B-raf (BRAF)	TTWCGQT	BRAF_HUMAN	Inhibitor	[2]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	Highest Status	REF
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Approved	[3]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	Highest Status	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Approved	[4]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[5]

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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
Serine/threonine-protein kinase B-raf (BRAF)	DTT	BRAF	6.409	7.097	6.062	6.049
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.009	6.988	7.442	8.135
Breast cancer resistance protein (ABCG2)	DTP	BCRP	6.732	7.513	6.326	9.277
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	9.791	3.744	3.413	1.609
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

Melanoma

ICD Disease Classification

2C30

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Serine/threonine-protein kinase B-raf (BRAF)	DTT	BRAF	3.00E-01	0.1	0.2
P-glycoprotein 1 (ABCB1)	DTP	P-GP	9.48E-02	1.45E-01	2.92E-01
Breast cancer resistance protein (ABCG2)	DTP	BCRP	5.25E-11	6.24E-01	9.23E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	6.39E-01	-5.46E-02	-2.77E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.75E-01	3.78E-02	1.44E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
2	Clinical pipeline report, company report or official report of GlaxoSmithKline (2011).
3	Mechanisms limiting distribution of the threonine-protein kinase B-RaF(V600E) inhibitor dabrafenib to the brain: implications for the treatment of melanoma brain metastases. J Pharmacol Exp Ther. 2013 Mar;344(3):655-64.
4	Physiologically based pharmacokinetic modeling to identify physiological and molecular characteristics driving variability in drug exposure. Clin Pharmacol Ther. 2018 Dec;104(6):1219-1228.
5	Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol Rev. 2016 Jan;68(1):168-241.