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

General Information of Drug (ID: DMR93MK)

• Drug Name: GRL-7234 Drug Info
• Synonyms: GRL-7234; N-[(1s,2s,4r)-2-Hydroxy-1-Isobutyl-5-({(1s)-1-[(Isopropylamino)carbonyl]-2-Methylpropyl}amino)-4-Methyl-5-Oxopentyl]-5-[methyl(Methylsulfonyl)amino]-N'-[(1r)-1-Phenylethyl]isophthalamide; 2p4j; Isophthalamide Derivative 5d; CHEMBL387771; BDBM16259; 23I; 1-N-[(1R,3S,4S)-3-hydroxy-1,6-dimethyl-1-{[(1S)-2-methyl-1-(propan-2-ylcarbamoyl)propyl]carbamoyl}heptan-4-yl]-5-(N-methylmethanesulfonamido)-3-N-[(1R)-1-phenylethyl]benzene-1,3-dicarboxamide

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 16659106
  TTD Drug ID: DMR93MK

Molecule-Related Drug Atlas

Drug(s) Targeting Cathepsin D (CTSD)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID10498202C1	DMXE0F2	Multiple sclerosis	8A40	Clinical trial	[2]
CI-992	DMBHYIJ	Hypertension	BA00-BA04	Terminated	[3]
Alpha-D-Mannose	DMF5DLW	Discovery agent	N.A.	Investigative	[4]
Grassystatin a	DM1PWX2	Discovery agent	N.A.	Investigative	[5]
PMID8410973C3	DM6J5KY	Discovery agent	N.A.	Investigative	[6]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[7]
S-Methylcysteine	DMAMRKS	Discovery agent	N.A.	Investigative	[4]
Carbocyclic Peptidomimetic	DM87SOX	Discovery agent	N.A.	Investigative	[8]
N-Aminoethylmorpholine	DMWXBYC	Discovery agent	N.A.	Investigative	[4]
1h-Benoximidazole-2-Carboxylic Acid	DMNZAVE	Discovery agent	N.A.	Investigative	[4]

Drug(s) Targeting Beta-secretase (BACE)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(S)-FLURBIPROFEN	DMF2O4T	Myalgia	FB56.2	Preregistration	[9]
E-2609	DMTNUJ8	Alzheimer disease	8A20	Phase 3	[10]
verubecestat	DM4CGH5	Alzheimer disease	8A20	Phase 3	[11]
Lanabecestat	DMFJLB6	Alzheimer disease	8A20	Phase 3	[12]
AZD3293	DMJQHXD	Alzheimer disease	8A20	Phase 2/3	[13]
JNJ-54861911	DMGPJ5U	Alzheimer disease	8A20	Phase 2/3	[12]
R-flurbiprofen	DMFIVSR	N. A.	N. A.	Phase 2	[9]
LY2886721	DMV14LM	Alzheimer disease	8A20	Phase 2	[14]
LY3202626	DM7IFNB	Alzheimer disease	8A20	Phase 2	[12]
AZD-3839	DM72FOD	Alzheimer disease	8A20	Phase 1	[15]

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]
Cathepsin D (CTSD)	TTPT2QI	CATD_HUMAN	Inhibitor	[1]

References

• [1] Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligands. J Med Chem. 2007 May 17;50(10):2399-407.
• [2] Synthesis and structure activity relationships of novel small molecule cathepsin D inhibitors. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2531-6.
• [3] Structure-activity relationships of a series of 2-amino-4-thiazole-containing renin inhibitors. J Med Chem. 1992 Jul 10;35(14):2562-72.
• [4] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [5] Grassystatins A-C from marine cyanobacteria, potent cathepsin E inhibitors that reduce antigen presentation. J Med Chem. 2009 Sep 24;52(18):5732-47.
• [6] Specificity in the binding of inhibitors to the active site of human/primate aspartic proteinases: analysis of P2-P1-P1'-P2' variation. J Med Chem. 1993 Sep 3;36(18):2614-20.
• [7] alpha-Substituted norstatines as the transition-state mimic in inhibitors of multiple digestive vacuole malaria aspartic proteases. Bioorg Med Chem. 2009 Aug 15;17(16):5933-49.
• [8] Structure-based design, synthesis, and memapsin 2 (BACE) inhibitory activity of carbocyclic and heterocyclic peptidomimetics. J Med Chem. 2005 Aug 11;48(16):5175-90.
• [9] 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.
• [10] Targeting the beta secretase BACE1 for Alzheimer's disease therapy. Lancet Neurol. 2014 March; 13(3): 319-329.
• [11] BACE1 inhibitor drugs in clinical trials for Alzheimer's disease. Alzheimers Res Ther. 2014 Dec 24;6(9):89.
• [12] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [13] 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.
• [14] Lessons from a BACE1 inhibitor trial: off-site but not off base.Alzheimers Dement.2014 Oct;10(5 Suppl):S411-9.
• [15] 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.