Details of the Drug

General Information of Drug (ID: DM471ZH)

Drug Name
ORE-1001
Synonyms
MLN-4760; UNII-4LD0ZHV25K; 4LD0ZHV25K; CHEMBL429844; MLN 4760; 305335-31-3; (S,S)-2-{1-CARBOXY-2-[3-(3,5-DICHLORO-BENZYL)-3H-IMIDAZOL-4-YL]-ETHYLAMINO}-4-METHYL-PENTANOIC ACID; XX5; N-[(1s)-1-carboxy-3-methylbutyl]-3-(3,5-dichlorobenzyl)-l-histidine; (2S)-2-[[(2S)-3-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]-1-hydroxy-1-oxopropan-2-yl]amino]-4-methylpentanoic acid; AC1L9LSK; GTPL7866; SCHEMBL1691048; BDBM21489; DTXSID70184609; ZINC1549629; DB12271; HY-19414; CS-0015513
Indication
Disease Entry ICD 11 Status REF
Diabetic complication 5A2Y Phase 1/2 [1]
Type-2 diabetes 5A11 Discontinued in Phase 1 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 428.3
Logarithm of the Partition Coefficient (xlogp) 1.4
Rotatable Bond Count (rotbonds) 10
Hydrogen Bond Donor Count (hbonddonor) 3
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C19H23Cl2N3O4
IUPAC Name
(2S)-2-[[(1S)-1-carboxy-2-[3-[(3,5-dichlorophenyl)methyl]imidazol-4-yl]ethyl]amino]-4-methylpentanoic acid
Canonical SMILES
CC(C)C[C@@H](C(=O)O)N[C@@H](CC1=CN=CN1CC2=CC(=CC(=C2)Cl)Cl)C(=O)O
InChI
InChI=1S/C19H23Cl2N3O4/c1-11(2)3-16(18(25)26)23-17(19(27)28)7-15-8-22-10-24(15)9-12-4-13(20)6-14(21)5-12/h4-6,8,10-11,16-17,23H,3,7,9H2,1-2H3,(H,25,26)(H,27,28)/t16-,17-/m0/s1
InChIKey
NTCCRGGIJNDEAB-IRXDYDNUSA-N
Cross-matching ID
PubChem CID
448281
ChEBI ID
CHEBI:166834
CAS Number
305335-31-3
DrugBank ID
DB12271
TTD ID
D08EYQ
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Angiotensin-converting enzyme 2 (ACE2) TTUI5H7 ACE2_HUMAN Inhibitor [3]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Angiotensin-converting enzyme (ACE) OTDF1964 ACE_HUMAN Gene/Protein Processing [4]
Angiotensin-converting enzyme 2 (ACE2) OTTRZGU7 ACE2_HUMAN Gene/Protein Processing [4]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Biochemical Pathways [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Diabetic complication
ICD Disease Classification 5A2Y
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Angiotensin-converting enzyme 2 (ACE2) DTT ACE2 3.93E-02 0.4 1.1
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT01039597) Safety and Activity of ORE1001 in Subjects With Ulcerative Colitis. U.S. National Institutes of Health.
2 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: 7866).
3 Effects of the ACE2 inhibitor GL1001 on acute dextran sodium sulfate-induced colitis in mice. Inflamm Res. 2009 Nov;58(11):819-27.
4 Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cells. Eur J Pharmacol. 2016 Mar 5;774:25-33. doi: 10.1016/j.ejphar.2016.01.007. Epub 2016 Feb 3.
5 Neprilysin is a Mediator of Alternative Renin-Angiotensin-System Activation in the Murine and Human Kidney. Sci Rep. 2016 Sep 21;6:33678. doi: 10.1038/srep33678.