Details of the Drug

General Information of Drug (ID: DMABRJL)

Drug Name

Ximelagatran

Synonyms

Exanta; Exarta; H 376/95; Ximelagatran [USAN:INN]; 192939-46-1; H 376-95; H 37695; Glycine, N-((1)1-cyclohexyl-2-((2)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-, ethyl ester; NCGC00183598-01; Ethyl (((1R)-1-cyclohexyl-2-((2S)-2-((4-(hydroxycarbamimidoyl)benzyl)carbamoyl)azetidin-1-yl-2-oxoethyl)amino)acetate; Glycine, N-((1R)-1-cyclohexyl-2-((2S)-2-((((4-(hydroxyamino)iminomethyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)-2-oxoethyl)-, ethyl ester; H 376 95; Exanta (TN); Exarta (TN); Xi-melagatran; H-376/95; Ximelagatran (JAN/USAN/INN); Glycine, N-((1)1-cyclohexyl-2-((2)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl ester; Glycine, N-((1R)1-cyclohexyl-2-((2S)-((((4-(amino(hydroxyimino)methyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)2-oxoethyl)-ethyl ester; Glycine, N-((1R)-1-cyclohexyl-2-((2S)-2-((((4-((hydroxyamino)iminomethyl)phenyl)methyl)amino)carbonyl)-1-azetidinyl)-2-oxoethyl)-, ester ester; H376/95

Indication

Disease Entry	ICD 11	Status	REF
Coagulation defect	3B10.0	Withdrawn from market	[1]
------------------------------------------------------------------------------------

Therapeutic Class

Anticoagulants

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 1

Molecular Weight (mw)

473.6

Logarithm of the Partition Coefficient (xlogp)

2.2

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Bioavailability: The bioavailability of drug is 20% []
Half-life: The concentration or amount of drug in body reduced by one-half in 3 - 5 hours [2]
Metabolism: The drug is metabolized via the liver []

Chemical Identifiers

Formula: C24H35N5O5
IUPAC Name: ethyl 2-[[(1R)-1-cyclohexyl-2-[(2S)-2-[[4-[(Z)-N'-hydroxycarbamimidoyl]phenyl]methylcarbamoyl]azetidin-1-yl]-2-oxoethyl]amino]acetate
Canonical SMILES: CCOC(=O)CN[C@H](C1CCCCC1)C(=O)N2CC[C@H]2C(=O)NCC3=CC=C(C=C3)/C(=N/O)/N
InChI: InChI=1S/C24H35N5O5/c1-2-34-20(30)15-26-21(17-6-4-3-5-7-17)24(32)29-13-12-19(29)23(31)27-14-16-8-10-18(11-9-16)22(25)28-33/h8-11,17,19,21,26,33H,2-7,12-15H2,1H3,(H2,25,28)(H,27,31)/t19-,21+/m0/s1
InChIKey: ZXIBCJHYVWYIKI-PZJWPPBQSA-N

Cross-matching ID

PubChem CID: 9574101
ChEBI ID: CHEBI:136702
CAS Number: 192939-46-1
DrugBank ID: DB04898
TTD ID: D0JQ7Y
VARIDT ID: DR01404
INTEDE ID: DR1720

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Coagulation factor IIa (F2)	TT6L509	THRB_HUMAN	Inhibitor	[3]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[4]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2C9 (CYP2C9)_{Main DME}	DE5IED8	CP2C9_HUMAN	Substrate	[5]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Prothrombin (F2)	OTNFSM49	THRB_HUMAN	Protein Interaction/Cellular Processes	[6]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Coagulation defect

ICD Disease Classification

3B10.0

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
P-glycoprotein 1 (ABCB1)	DTP	P-GP	7.23E-01	-8.20E-02	-3.22E-01
Cytochrome P450 2C9 (CYP2C9)	DME	CYP2C9	9.09E-01	-9.26E-02	-3.68E-01

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

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: 6381).
2	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
3	Ximelagatran increases membrane fluidity and changes membrane lipid composition in primary human hepatocytes. Toxicol In Vitro. 2009 Oct;23(7):1305-10.
4	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
5	Comparative pharmacokinetics of vitamin K antagonists: warfarin, phenprocoumon and acenocoumarol. Clin Pharmacokinet. 2005;44(12):1227-46.
6	Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction. J Thromb Haemost. 2005 Oct;3(10):2245-53. doi: 10.1111/j.1538-7836.2005.01557.x.