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

General Information of Drug (ID: DM51LTG)

• Drug Name: BMS-708163 Drug Info
• Synonyms: Avagacestat

Indication

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[1]

• Cross-matching ID:
  PubChem CID: 46883536
  CAS Number: CAS 1146699-66-2
  TTD Drug ID: DM51LTG

Molecule-Related Drug Atlas

Drug(s) Targeting Gamma-secretase (GS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nirogacestat	DMUP5Z0	Desmoid tumour	2F7C	Approved	[3]
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[4]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[5]
Semagacestat	DML83IW	Parkinson disease	8A00.0	Phase 3	[6]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[4]
MK-0752	DMLTAES	Alzheimer disease	8A20	Phase 2	[7]
CHF-5074	DMTE071	Alzheimer disease	8A20	Phase 2	[8]
RO-4929097	DMXA6B3	Breast cancer	2C60-2C65	Phase 2	[9]
AL102	DMCTWIB	Desmoid tumour	2F7C	Phase 2	[10]
SPI-014	DM5IPUS	Alzheimer disease	8A20	Phase 1	[11]

Molecular Interaction Atlas of 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]

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: 6489).
• [2] 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.
• [3] Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
• [4] 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.
• [5] Clinical pipeline report, company report or official report of Roche (2009).
• [6] A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
• [7] 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.
• [8] 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.
• [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] Clinical pipeline report, company report or official report of Ayala Pharmaceuticals.
• [11] Modulation of gamma-secretase for the treatment of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:210756.