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

General Information of Drug (ID: DMFIVSR)

• Drug Name: R-flurbiprofen Drug Info
• Synonyms: Tarenflurbil; (R)-Flurbiprofen; 51543-40-9; Flurizan; R-Flurbiprofen; (R)-2-Flurbiprofen; (R)-2-Flubiprofen; MPC-7869; UNII-501W00OOWA; R-(-)-Flurbiprofen; (2r)-2-(3-Fluoro-4-Phenyl-Phenyl)propanoic Acid; (-)-(2R)-2-(2-fluorobiphenyl-4-yl)propanoic acid; (R)-(-)-2-Fluoro-alpha-methyl-4-biphenylacetic acid; (R)-2-Fluoro-alpha-methyl(1,1'-biphenyl)-4-acetic acid; (2R)-2-(2-fluorobiphenyl-4-yl)propanoic acid; (2R)-2-(3-fluoro-4-phenylphenyl)propanoic acid; CHEMBL190083; 501W00OOWA; CHEBI:38666; E-7869
• Cross-matching ID:
  PubChem CID: 92337
  ChEBI ID: CHEBI:38666
  CAS Number: CAS 51543-40-9
  TTD Drug ID: DMFIVSR

Molecule-Related Drug Atlas

Drug(s) Targeting Beta-secretase (BACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
E-2609	DMTNUJ8	Alzheimer disease	8A20	Phase 3	[2]
verubecestat	DM4CGH5	Alzheimer disease	8A20	Phase 3	[3]
Lanabecestat	DMFJLB6	Alzheimer disease	8A20	Phase 3	[4]
AZD3293	DMJQHXD	Alzheimer disease	8A20	Phase 2/3	[5]
JNJ-54861911	DMGPJ5U	Alzheimer disease	8A20	Phase 2/3	[4]
LY2886721	DMV14LM	Alzheimer disease	8A20	Phase 2	[6]
LY3202626	DM7IFNB	Alzheimer disease	8A20	Phase 2	[4]
AZD-3839	DM72FOD	Alzheimer disease	8A20	Phase 1	[7]
LY-2811376	DM8LGWR	Alzheimer disease	8A20	Phase 1	[8]

Drug(s) Targeting Presenilin 1 (PSEN1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone	DMREVX9	Discovery agent	N.A.	Investigative	[9]
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone	DMHG7MU	Discovery agent	N.A.	Investigative	[9]
Drug 311951	DMXTCJ1	Discovery agent	N.A.	Investigative	[10]
Drug 311383	DM5QUJV	Discovery agent	N.A.	Investigative	[10]
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one	DMF9X2T	Discovery agent	N.A.	Investigative	[9]
(2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone	DMJE83O	Discovery agent	N.A.	Investigative	[9]
Drug 311952	DM27ILS	Discovery agent	N.A.	Investigative	[10]
Drug 311440	DMOIFBK	Discovery agent	N.A.	Investigative	[10]
1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene	DM13HGN	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Presenilin 2 (PSEN2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
(5R,6S)-5,6-bis(benzyloxy)cyclohex-2-enone	DMREVX9	Discovery agent	N.A.	Investigative	[9]
(5R,6S)-6-(benzyloxy)-5-methoxycyclohex-2-enone	DMHG7MU	Discovery agent	N.A.	Investigative	[9]
Drug 311951	DMXTCJ1	Discovery agent	N.A.	Investigative	[10]
Drug 311383	DM5QUJV	Discovery agent	N.A.	Investigative	[10]
1-benzoyl-2-benzyl-1,2-dihydropyridin-3(6H)-one	DMF9X2T	Discovery agent	N.A.	Investigative	[9]
(2S,3R)-2-(benzyloxy)-3-methoxycyclohexanone	DMJE83O	Discovery agent	N.A.	Investigative	[9]
Drug 311952	DM27ILS	Discovery agent	N.A.	Investigative	[10]
Drug 311440	DMOIFBK	Discovery agent	N.A.	Investigative	[10]
1-Chloro-4-(1-phenyl-cyclohexanesulfonyl)-benzene	DM13HGN	Discovery agent	N.A.	Investigative	[11]

Drug(s) Targeting Gamma-secretase (GS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Nirogacestat	DMUP5Z0	Desmoid tumour	2F7C	Approved	[12]
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[1]
AMG 386	DMQJXL4	Breast cancer	2C60-2C65	Phase 3	[13]
Semagacestat	DML83IW	Parkinson disease	8A00.0	Phase 3	[14]
MK-0752	DMLTAES	Alzheimer disease	8A20	Phase 2	[15]
BMS-708163	DM51LTG	Alzheimer disease	8A20	Phase 2	[16]
CHF-5074	DMTE071	Alzheimer disease	8A20	Phase 2	[17]
RO-4929097	DMXA6B3	Breast cancer	2C60-2C65	Phase 2	[18]
AL102	DMCTWIB	Desmoid tumour	2F7C	Phase 2	[19]
SPI-014	DM5IPUS	Alzheimer disease	8A20	Phase 1	[20]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Beta-secretase (BACE)	TT8JRS7	NOUNIPROTAC	Inhibitor	[1]
Gamma-secretase (GS)	TT9W8GU	APH1A_HUMAN; APH1B_HUMAN; PEN2_HUMAN; NICA_HUMAN; PSN1_HUMAN	Inhibitor	[1]
Presenilin 1 (PSEN1)	TTZ3S8C	PSN1_HUMAN	Inhibitor	[1]
Presenilin 2 (PSEN2)	TTWN3F4	PSN2_HUMAN	Inhibitor	[1]

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] Targeting the beta secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014 March; 13(3): 319-329.
• [3] BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. Alzheimers Res Ther. 2014 Dec 24;6(9):89.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] AZD3293 A novel BACE1 inhibitor: safety, tolerability, and effects on plasma and CSF A-beta peptides following single- and multiple-dose administration. Neurobiology of Aging. May 20, 2008.
• [6] Lessons from a BACE1 inhibitor trial: off-site but not off base.Alzheimers Dement.2014 Oct;10(5 Suppl):S411-9.
• [7] Discovery of AZD3839, a potent and selective BACE1 inhibitor clinical candidate for the treatment of Alzheimer disease. J Biol Chem. 2012 Nov 30;287(49):41245-57.
• [8] Neurodegenerative disease: Inhibiting beta-secretase in humans. Nature Reviews Drug Discovery 11, 21 (January 2012).
• [9] 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.
• [10] Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase. J Med Chem. 2004 Jul 29;47(16):3931-3.
• [11] Aryl sulfones: a new class of gamma-secretase inhibitors. Bioorg Med Chem Lett. 2005 May 16;15(10):2685-8.
• [12] Pharmacodynamics and pharmacokinetics of the gamma-secretase inhibitor PF-3084014.J Pharmacol Exp Ther.2010 Jul;334(1):269-77.
• [13] Clinical pipeline report, company report or official report of Roche (2009).
• [14] A phase 3 trial of semagacestat for treatment of Alzheimer's disease. N Engl J Med. 2013 Jul 25;369(4):341-50.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] 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.
• [19] Clinical pipeline report, company report or official report of Ayala Pharmaceuticals.
• [20] Modulation of gamma-secretase for the treatment of Alzheimer's disease. Int J Alzheimers Dis. 2012;2012:210756.