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

General Information of DTT (ID: TT9W8GU)

• DTT Name: Gamma-secretase (GS) DTT Info
• UniProt ID: APH1A_HUMAN; APH1B_HUMAN; PEN2_HUMAN; NICA_HUMAN; PSN1_HUMAN
• Gene Name: APH1A; APH1B; NCSTN; PSENEN; PSEN1

Molecule-Related Drug & Molecule List

18 Clinical Trial Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[2]
PF-03084014	DMUP5Z0	Desmoid tumour	2F7C	Phase 3	[3]
Semagacestat	DML83IW	Parkinson disease	8A00.0	Phase 3	[4]
AL102	DMCTWIB	Desmoid tumour	2F7C	Phase 2	[5]
BMS-708163	DM51LTG	Alzheimer disease	8A20	Phase 2	[6]
CHF-5074	DMTE071	Alzheimer disease	8A20	Phase 2	[7]
MK-0752	DMLTAES	Alzheimer disease	8A20	Phase 2	[8]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[1]
RO-4929097	DMXA6B3	Breast cancer	2C60-2C65	Phase 2	[9], [10]
Begacestat	DMUR49N	Alzheimer disease	8A20	Phase 1	[11]
E-2212	DMQDKYV	Alzheimer disease	8A20	Phase 1	[12]
E2012	DMNEVKA	Alzheimer disease	8A20	Phase 1	[13], [14]
GSI-136	DMSR5HD	Alzheimer disease	8A20	Phase 1	[15]
NGP 555	DMTVQH2	Alzheimer disease	8A20	Phase 1	[16]
PF-06648671	DMGUKRN	Alzheimer disease	8A20	Phase 1	[16]
PF-06648671	DM056JD	Alzheimer disease	8A20	Phase 1	[17]
SPI-014	DM5IPUS	Alzheimer disease	8A20	Phase 1	[18]

8 Investigative Drug(s) Transported by This DTP

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone	DMJE83O	Discovery agent	N.A.	Investigative	[19]
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone	DMREVX9	Discovery agent	N.A.	Investigative	[19]
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone	DMHG7MU	Discovery agent	N.A.	Investigative	[19]
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one	DMF9X2T	Discovery agent	N.A.	Investigative	[19]
Drug 311383	DM5QUJV	Discovery agent	N.A.	Investigative	[20]
Drug 311440	DMOIFBK	Discovery agent	N.A.	Investigative	[20]
Drug 311951	DMXTCJ1	Discovery agent	N.A.	Investigative	[20]
Drug 311952	DM27ILS	Discovery agent	N.A.	Investigative	[20]

References

• [1] The geminal dimethyl analogue of Flurbiprofen as a novel Abeta42 inhibitor and potential Alzheimer's disease modifying agent. Bioorg Med Chem Lett. 2006 Apr 15;16(8):2219-23.
• [2] Clinical pipeline report, company report or official report of Roche (2009).
• [3] Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
• [4] A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
• [5] Clinical pipeline report, company report or official report of Ayala Pharmaceuticals.
• [6] Safety and tolerability of the gamma-secretase inhibitor avagacestat in a phase 2 study of mild to moderate Alzheimer disease. Arch Neurol. 2012 Nov;69(11):1430-40.
• [7] CHF5074, a novel gamma-secretase modulator, attenuates brain beta-amyloid pathology and learning deficit in a mouse model of Alzheimer's disease.Br J Pharmacol.2009 Mar;156(6):982-93.
• [8] Determination of the gamma-secretase inhibitor MK-0752 in human plasma by online extraction and electrospray tandem mass spectrometry (HTLC-ESI-MS/MS). J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 1;878(25):2348-52.
• [9] Phase I study of RO4929097, a gamma secretase inhibitor of Notch signaling, in patients with refractory metastatic or locally advanced solid tumors. J Clin Oncol. 2012 Jul 1;30(19):2348-53.
• [10] Phase 2 study of RO4929097, a gamma-secretase inhibitor, in metastatic melanoma: SWOG 0933.Cancer.2015 Feb 1;121(3):432-440.
• [11] Begacestat (GSI-953): a novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein gamma-secretase for the treatment of Alzheimer's disease. J Pharmacol Exp Ther. 2009 Nov;331(2):598-608.
• [12] Development and mechanism of gamma-secretase modulators for Alzheimer's disease. Biochemistry. 2013 May 14;52(19):3197-216.
• [13] Chemical Biology, Molecular Mechanism and Clinical Perspective of -Secretase Modulators in Alzheimer's Disease.Curr Neuropharmacol.2011 Dec;9(4):598-622.
• [14] Lactams as beta secretase inhibitors
• [15] Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Pharmacokinetic and Pharmacodynamic Effects of a -Secretase Modulator, PF-06648671, on CSF Amyloid- Peptides in Randomized Phase I Studies. Clin Pharmacol Ther. 2020 Jan;107(1):211-220.
• [18] Modulation of gamma-secretase for the treatment of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:210756.
• [19] Novel gamma-secretase inhibitors discovered by library screening of in-house synthetic natural product intermediates. Bioorg Med Chem Lett. 2006 Jul 15;16(14):3813-6.
• [20] Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J Med Chem. 2004 Jul 29;47(16):3931-3.