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

General Information of Drug (ID: DML83IW)

Drug Name

Semagacestat Drug Info

Synonyms

DAPT; AN-37124; AN-44989; LY-374973; LY-411575; LY-424354; LY-450139; LY-4501395; Gamma-secretase inhibitors (Alzheimer's disease), Elan Pharmaceuticals/Eli Lilly

Indication

Disease Entry	ICD 11	Status	REF
Parkinson disease	8A00.0	Phase 3	[1]

Cross-matching ID

PubChem CID: 9843750
ChEBI ID: CHEBI:131158
CAS Number: CAS 425386-60-3
TTD Drug ID: DML83IW
INTEDE Drug ID: DR1888

Molecule(s) Related to This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Gamma-secretase (GS)	TT9W8GU	APH1A_HUMAN; APH1B_HUMAN; PEN2_HUMAN; NICA_HUMAN; PSN1_HUMAN	Modulator	[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 3	[3]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Phase 3	[3]

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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
Gamma-secretase (GS)	DTT	APH1A	7.23	7.775	7.538	7.928
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	10.08	7.207	5.403	9.211
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

Parkinson disease

ICD Disease Classification

8A00.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Gamma-secretase (GS)	DTT	APH1A; APH1B; NCSTN; PSENEN; PSEN1	1.47E-02	-0.09	-0.37
Cytochrome P450 3A5 (CYP3A5)	DME	CYP3A5	9.96E-01	-3.17E-03	-1.84E-02
Cytochrome P450 3A4 (CYP3A4)	DME	CYP3A4	1.04E-02	6.29E-02	3.54E-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: 6978).
2	A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
3	Disposition and metabolism of semagacestat, a {gamma}-secretase inhibitor, in humans. Drug Metab Dispos. 2010 Apr;38(4):554-65.