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

General Information of Drug (ID: DMMOPAK)

• Drug Name: E-64 Drug Info
• Synonyms: e-64; 66701-25-5; CHEMBL189382; AC1NEEQI; SCHEMBL13283063; HMS3369L13; trans-Epoxysuccinyl-leucylamido-[4-guanidino]butane; [L-3-trans-carboxy-oxiran-2-carbonyl]-Leu-agmatin; trans-Epoxysuccinyl-leucylamido- [4-guanidino]butane; [L -3-trans-carboxy- oxiran-2-carbonyl]-Leu-agmatin; 3-({1-[(4-carbamimidamidobutyl)carbamoyl]-3-methylbutyl}carbamoyl)oxirane-2-carboxylic acid; 3-[[1-[4-(diaminomethylideneamino)butylamino]-4-methyl-1-oxopentan-2-yl]carbamoyl]oxirane-2-carboxylic acid

Indication

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

• Cross-matching ID:
  PubChem CID: 123985
  ChEBI ID: CHEBI:30270
  CAS Number: CAS 66701-25-5
  TTD Drug ID: DMMOPAK

Molecule-Related Drug Atlas

Drug(s) Targeting Plasmodium Plasmepsin 2 (Malaria PLA2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9353089, 135	DMWG98Z	N. A.	N. A.	Patented	[4]
US9353089, 330	DMK02LS	N. A.	N. A.	Patented	[4]
US9353089, 327	DMB4MJ0	N. A.	N. A.	Patented	[4]
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[5]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[5]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[6]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[7]
PS-662477	DMT4YFR	Discovery agent	N.A.	Investigative	[8]
KNI-10740	DMPWY6H	Discovery agent	N.A.	Investigative	[6]
KNI-10265	DMQLB3T	Discovery agent	N.A.	Investigative	[9]

Drug(s) Targeting Plasmodium Plasmepsin 1 (Malaria PLA1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pepstatin	DM9S1EA	Malaria	1F40-1F45	Terminated	[5]
Leupeptin	DMU075F	Malaria	1F40-1F45	Investigative	[5]
KNI-10006	DMMISH6	Discovery agent	N.A.	Investigative	[10]
PS-777621	DM3F7SD	Discovery agent	N.A.	Investigative	[7]
SC-5003	DM2DU80	Discovery agent	N.A.	Investigative	[11]
L-mannitol derivative	DMK12C0	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting Cathepsin S (CTSS)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7625	DMDGPKS	Autoimmune disease	4A40-4A45	Phase 2	[13]
SAR-114137	DMZ1XR5	Pain	MG30-MG3Z	Phase 1	[14]
VBY- 891	DMTKPH4	Autoimmune diabetes	5A10	Phase 1	[15]
VBY- 036	DMULRYC	Neuropathic pain	8E43.0	Phase 1	[16]
VBY-129	DM4YIWK	Autoimmune diabetes	5A10	Phase 1	[17]
PMID27998201-Compound-12	DM8QZNC	Bone cancer	2B5Z	Patented	[18]
PMID27998201-Compound-5	DMVZ0ND	Chronic obstructive pulmonary disease	CA22	Patented	[18]
PMID27998201-Compound-9	DM1JOZN	Rheumatoid arthritis	FA20	Patented	[18]
PMID25399719-Compound-17	DMRXKJZ	N. A.	N. A.	Patented	[19]
PMID27998201-Compound-17	DMAZVHJ	Hair loss	ED70	Patented	[18]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cathepsin S (CTSS)	TTUMQVO	CATS_HUMAN	Inhibitor	[1]
Plasmodium Plasmepsin 1 (Malaria PLA1)	TTH9VL3	PLM1_PLAFA	Inhibitor	[2]
Plasmodium Plasmepsin 2 (Malaria PLA2)	TTXMNHO	PLM2_PLAFA	Inhibitor	[2]
Virus Cysteine proteinase (Viru VCATH)	TTREV7X	CATV_GVCPM	Inhibitor	[3]

References

• [1] Baculoviral expression and characterization of rodent cathepsin S. Protein Expr Purif. 2001 Oct;23(1):45-54.
• [2] Antimalarial synergy of cysteine and aspartic protease inhibitors. Antimicrob Agents Chemother. 1998 Sep;42(9):2254-8.
• [3] Characterization of a cysteine proteinase from Taenia crassiceps cysts. Mol Biochem Parasitol. 1997 Apr;85(2):243-53.
• [4] Compositions and methods for the treatment of malaria. US9353089.
• [5] Novel molecular targets for antimalarial chemotherapy. Int J Antimicrob Agents. 2007 Jul;30(1):4-10.
• [6] Improvement of both plasmepsin inhibitory activity and antimalarial activity by 2-aminoethylamino substitution. Bioorg Med Chem Lett. 2010 Aug 15;20(16):4836-9.
• [7] High antiplasmodial activity of novel plasmepsins I and II inhibitors. J Med Chem. 2006 Dec 14;49(25):7440-9.
• [8] Identification of potent inhibitors of Plasmodium falciparum plasmepsin II from an encoded statine combinatorial library. Bioorg Med Chem Lett. 1998 Sep 8;8(17):2315-20.
• [9] Antimalarial activity enhancement in hydroxymethylcarbonyl (HMC) isostere-based dipeptidomimetics targeting malarial aspartic protease plasmepsin. Bioorg Med Chem. 2008 Dec 1;16(23):10049-60.
• [10] 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.
• [11] Protease inhibitors: current status and future prospects. J Med Chem. 2000 Feb 10;43(3):305-41.
• [12] Synthesis of malarial plasmepsin inhibitors and prediction of binding modes by molecular dynamics simulations. J Med Chem. 2005 Sep 22;48(19):6090-106.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] From laboratory to pilot plant: the solid-state process development of a highly potent cathepsin S/K inhibitor. Eur J Pharm Biopharm. 2013 Apr;83(3):436-48.
• [15] 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. (Target id: 2353).
• [16] Clinical pipeline report, company report or official report of ViroBay.
• [17] Clinical pipeline report, company report or official report of ViroBay.
• [18] Cathepsin B and L inhibitors: a patent review (2010 - present).Expert Opin Ther Pat. 2017 Jun;27(6):643-656.
• [19] An updated patent review of calpain inhibitors (2012 - 2014).Expert Opin Ther Pat. 2015 Jan;25(1):17-31.