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

General Information of Drug (ID: DM3BH1Y)

Drug Name

Lapatinib Drug Info

Synonyms

FMM; Tycerb; Lapatinib Ditosylate; Lapatinib [INN]; Lapatinib tosilate hydrate; GSK 572016; GSK572016; GW 572016; GW 572016X; GW572016; Lapatinib (INN); Tykerb (TN); Lapatinib, Tykerb, GW572016; N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]furan-2-yl]quinazolin-4-amine; N-{3-CHLORO-4-[(3-FLUOROBENZYL)OXY]PHENYL}-6-[5-({[2-(METHYLSULFONYL)ETHYL]AMINO}METHYL)-2-FURYL]-4-QUINAZOLINAMINE; N-(3-Chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-((2-methylsulfonylethylamino)methyl)-2-furyl)quinazolin-4-amine; N-(3-Chloro-4-{[(3-fluorophenyl)methyl]oxy}phenyl)-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furanyl]-4-quinazolinamine; 4-[[3-Chloro-4-(3-fluorobenzyloxy)phenyl]amino]-6-[5-[[(2-methanesulfonylethyl)amino]methyl]furan-2-yl]quinazoline; Lapatinib (ERBB2 inhibitor)

Indication

Disease Entry	ICD 11	Status	REF
Breast cancer	2C60-2C65	Approved	[1]
Gastroesophageal junction adenocarcinoma	2B71	Approved	[2]
Melanoma	2C30	Approved	[2]

Therapeutic Class

Anticancer Agents

Cross-matching ID

PubChem CID: 208908
ChEBI ID: CHEBI:49603
CAS Number: CAS 231277-92-2
TTD Drug ID: DM3BH1Y
VARIDT Drug ID: DR00120
INTEDE Drug ID: DR0917
ACDINA Drug ID: D00351

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Epidermal growth factor receptor (EGFR)	TTGKNB4	EGFR_HUMAN	Inhibitor	[3]
Erbb2 tyrosine kinase receptor (HER2)	TT6EO5L	ERBB2_HUMAN	Inhibitor	[3]
Eukaryotic elongation factor 2 kinase (eEF-2K)	TT1QFLA	EF2K_HUMAN	Inhibitor	[4]

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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	[5]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Approved	[6]

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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	[7]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Approved	[8]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Approved	[8]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Approved	[7]

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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
Epidermal growth factor receptor (EGFR)	DTT	EGFR	6.045	4.991	5.317	5.252
Erbb2 tyrosine kinase receptor (HER2)	DTT	ERBB2	6.226	7.169	7.196	6.397
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 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	7.867	5.142	5.52	7.08
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

Breast cancer

ICD Disease Classification

2C60-2C65

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Epidermal growth factor receptor (EGFR)	DTT	EGFR	5.84E-05	0.32	0.55
P-glycoprotein 1 (ABCB1)	DTP	P-GP	1.42E-02	-2.10E-01	-5.11E-01
Breast cancer resistance protein (ABCG2)	DTP	BCRP	1.07E-06	-3.94E-01	-6.94E-01
Cytochrome P450 2C8 (CYP2C8)	DME	CYP2C8	2.90E-11	-1.06E-01	-1.42E-01
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	2.45E-13	-2.29E+00	-1.44E+00
Mephenytoin 4-hydroxylase (CYP2C19)	DME	CYP2C19	1.49E-08	-1.53E-01	-6.35E-01
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	5.04E-04	-9.90E-02	-3.91E-01

Molecular Expression Atlas between Disease Section and Healthy Individual Tissue

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5692).
2	Lapatinib FDA Label
3	Triple negative breast cancer--current status and prospective targeted treatment based on HER1 (EGFR), TOP2A and C-MYC gene assessment. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2009 Mar;153(1):13-7.
4	Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways.BMC Cancer. 2016 Oct 19;16(1):813.
5	The role of efflux and uptake transporters in [N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, lapatinib) disposition and drug interactions. Drug Metab Dispos. 2008 Apr;36(4):695-701.
6	Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
7	Mechanism-based inactivation of cytochrome P450 3A4 by lapatinib. Mol Pharmacol. 2010 Oct;78(4):693-703.
8	Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706.