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Identification
NameUbenimex
Accession NumberDB03424  (EXPT00673)
TypeSmall Molecule
GroupsExperimental
DescriptionUbenimex (also known as bestatin) is a competitive protease inhibitor. It is an inhibitor of aminopeptidase B, leukotriene A4 hydrolase, aminopeptidase N. It is being studied for use in the treatment of acute myelocytic leukemia.
Structure
Thumb
Synonyms
Bestatin
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
BestatinNippon Kayaku, Japan
Brand mixturesNot Available
SaltsNot Available
Categories
UNIII0J33N5627
CAS number58970-76-6
WeightAverage: 308.3728
Monoisotopic: 308.173607266
Chemical FormulaC16H24N2O4
InChI KeyVGGGPCQERPFHOB-RDBSUJKOSA-N
InChI
InChI=1S/C16H24N2O4/c1-10(2)8-13(16(21)22)18-15(20)14(19)12(17)9-11-6-4-3-5-7-11/h3-7,10,12-14,19H,8-9,17H2,1-2H3,(H,18,20)(H,21,22)/t12-,13+,14+/m1/s1
IUPAC Name
(2S)-2-{[(2S,3R)-3-amino-1,2-dihydroxy-4-phenylbutylidene]amino}-4-methylpentanoic acid
SMILES
[H][C@@](N)(CC1=CC=CC=C1)[C@]([H])(O)C(O)=N[C@@]([H])(CC(C)C)C(O)=O
Pharmacology
IndicationAn adjuvant therapy used for acute and chronic myelonous leukemia, lung cancer and nasopharyngeal cancer. It is also used to treat hypercholesterolaemia.
Structured Indications Not Available
PharmacodynamicsNot Available
Mechanism of action
TargetKindPharmacological actionActionsOrganismUniProt ID
Bacterial leucyl aminopeptidaseProteinunknownNot AvailableVibrio proteolyticusQ01693 details
Leukotriene A-4 hydrolaseProteinunknownNot AvailableHumanP09960 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AbacavirThe serum concentration of Abacavir can be decreased when it is combined with Ubenimex.Approved, Investigational
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ubenimex.Approved
AlfuzosinThe serum concentration of Alfuzosin can be increased when it is combined with Ubenimex.Approved, Investigational
AlprazolamThe serum concentration of Alprazolam can be increased when it is combined with Ubenimex.Approved, Illicit, Investigational
Ambroxol acefyllinateThe serum concentration of Ambroxol acefyllinate can be decreased when it is combined with Ubenimex.Experimental
AmineptineThe serum concentration of Amineptine can be increased when it is combined with Ubenimex.Illicit, Withdrawn
AminophyllineThe serum concentration of Aminophylline can be decreased when it is combined with Ubenimex.Approved
AmitriptylineThe serum concentration of Amitriptyline can be increased when it is combined with Ubenimex.Approved
AnvirzelAnvirzel may decrease the cardiotoxic activities of Ubenimex.Investigational
AtorvastatinThe serum concentration of Atorvastatin can be increased when it is combined with Ubenimex.Approved
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Ubenimex.Investigational
BevacizumabBevacizumab may increase the cardiotoxic activities of Ubenimex.Approved, Investigational
BoceprevirThe serum concentration of Ubenimex can be decreased when it is combined with Boceprevir.Approved
BromocriptineThe serum concentration of Bromocriptine can be increased when it is combined with Ubenimex.Approved, Investigational
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Ubenimex.Approved
CabergolineThe serum concentration of Cabergoline can be increased when it is combined with Ubenimex.Approved
CarbamazepineThe metabolism of Ubenimex can be increased when combined with Carbamazepine.Approved, Investigational
ChlorotrianiseneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Ubenimex.Withdrawn
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Ubenimex.Approved, Investigational, Withdrawn
ClarithromycinThe therapeutic efficacy of Clarithromycin can be decreased when used in combination with Ubenimex.Approved
ClomipramineThe serum concentration of Clomipramine can be increased when it is combined with Ubenimex.Approved, Vet Approved
Conjugated Equine EstrogensThe serum concentration of Conjugated Equine Estrogens can be decreased when it is combined with Ubenimex.Approved
CyclobenzaprineThe serum concentration of Cyclobenzaprine can be increased when it is combined with Ubenimex.Approved
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Ubenimex.Approved, Investigational
CyclosporineThe serum concentration of Cyclosporine can be increased when it is combined with Ubenimex.Approved, Investigational, Vet Approved
DelavirdineThe serum concentration of Delavirdine can be decreased when it is combined with Ubenimex.Approved
DesipramineThe serum concentration of Desipramine can be increased when it is combined with Ubenimex.Approved
DeslanosideDeslanoside may decrease the cardiotoxic activities of Ubenimex.Approved
DienestrolThe serum concentration of Dienestrol can be decreased when it is combined with Ubenimex.Approved
DiethylstilbestrolThe serum concentration of Diethylstilbestrol can be decreased when it is combined with Ubenimex.Approved
DigitoxinDigitoxin may decrease the cardiotoxic activities of Ubenimex.Approved
DigoxinThe serum concentration of Digoxin can be increased when it is combined with Ubenimex.Approved
DihydroergotamineThe serum concentration of Dihydroergotamine can be increased when it is combined with Ubenimex.Approved
DiltiazemThe metabolism of Diltiazem can be decreased when combined with Ubenimex.Approved
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Ubenimex.Approved, Investigational
DosulepinThe serum concentration of Dosulepin can be increased when it is combined with Ubenimex.Approved
DoxepinThe serum concentration of Doxepin can be increased when it is combined with Ubenimex.Approved
DyphyllineThe serum concentration of Dyphylline can be decreased when it is combined with Ubenimex.Approved
EnfuvirtideThe serum concentration of Enfuvirtide can be increased when it is combined with Ubenimex.Approved, Investigational
Ergoloid mesylateThe serum concentration of Ergoloid mesylate can be increased when it is combined with Ubenimex.Approved
ErgonovineThe serum concentration of Ergonovine can be increased when it is combined with Ubenimex.Approved
ErgotamineThe serum concentration of Ergotamine can be increased when it is combined with Ubenimex.Approved
EsmirtazapineThe serum concentration of Esmirtazapine can be increased when it is combined with Ubenimex.Investigational
EstradiolThe serum concentration of Estradiol can be decreased when it is combined with Ubenimex.Approved, Investigational, Vet Approved
EstramustineThe serum concentration of Estramustine can be decreased when it is combined with Ubenimex.Approved
Estrogens, esterifiedThe serum concentration of Estrogens, esterified can be decreased when it is combined with Ubenimex.Approved
Estrone sulfateThe serum concentration of Estrone sulfate can be decreased when it is combined with Ubenimex.Approved
Ethinyl EstradiolThe serum concentration of Ethinyl Estradiol can be decreased when it is combined with Ubenimex.Approved
EtravirineThe serum concentration of Etravirine can be decreased when it is combined with Ubenimex.Approved
GarlicThe serum concentration of Ubenimex can be decreased when it is combined with Garlic.Approved
HexestrolThe serum concentration of Hexestrol can be decreased when it is combined with Ubenimex.Withdrawn
ImipramineThe serum concentration of Imipramine can be increased when it is combined with Ubenimex.Approved
LovastatinThe serum concentration of Lovastatin can be increased when it is combined with Ubenimex.Approved, Investigational
MestranolThe serum concentration of Mestranol can be decreased when it is combined with Ubenimex.Approved
MethallenestrilThe serum concentration of Methallenestril can be decreased when it is combined with Ubenimex.Experimental
MidazolamThe serum concentration of Midazolam can be increased when it is combined with Ubenimex.Approved, Illicit
MirtazapineThe serum concentration of Mirtazapine can be increased when it is combined with Ubenimex.Approved
NefazodoneThe serum concentration of Nefazodone can be increased when it is combined with Ubenimex.Approved, Withdrawn
NortriptylineThe serum concentration of Nortriptyline can be increased when it is combined with Ubenimex.Approved
OpipramolThe serum concentration of Opipramol can be increased when it is combined with Ubenimex.Investigational
OuabainOuabain may decrease the cardiotoxic activities of Ubenimex.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Ubenimex.Approved, Vet Approved
PethidineThe risk or severity of adverse effects can be increased when Ubenimex is combined with Pethidine.Approved
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Ubenimex.Approved
PimozideThe serum concentration of Pimozide can be increased when it is combined with Ubenimex.Approved
ProtriptylineThe serum concentration of Protriptyline can be increased when it is combined with Ubenimex.Approved
RiociguatThe serum concentration of Riociguat can be increased when it is combined with Ubenimex.Approved
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Ubenimex.Approved
SildenafilThe serum concentration of Sildenafil can be increased when it is combined with Ubenimex.Approved, Investigational
SimeprevirThe serum concentration of Simeprevir can be increased when it is combined with Ubenimex.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Ubenimex.Approved
St. John's WortThe metabolism of Ubenimex can be increased when combined with St. John's Wort.Nutraceutical
Synthetic Conjugated Estrogens, AThe serum concentration of Synthetic Conjugated Estrogens, A can be decreased when it is combined with Ubenimex.Approved
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Ubenimex.Approved, Investigational
TemsirolimusThe risk or severity of adverse effects can be increased when Ubenimex is combined with Temsirolimus.Approved
TheophyllineThe serum concentration of Theophylline can be decreased when it is combined with Ubenimex.Approved
TianeptineThe serum concentration of Tianeptine can be increased when it is combined with Ubenimex.Approved
TipranavirThe serum concentration of Ubenimex can be decreased when it is combined with Tipranavir.Approved, Investigational
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Ubenimex.Approved, Investigational
TriazolamThe serum concentration of Triazolam can be increased when it is combined with Ubenimex.Approved
TrimipramineThe serum concentration of Trimipramine can be increased when it is combined with Ubenimex.Approved
Valproic AcidThe serum concentration of Valproic Acid can be decreased when it is combined with Ubenimex.Approved, Investigational
VerapamilThe metabolism of Verapamil can be decreased when combined with Ubenimex.Approved
ZidovudineThe serum concentration of Zidovudine can be decreased when it is combined with Ubenimex.Approved
Food InteractionsNot Available
References
Synthesis Reference

Hamao Umezawa, Takaaki Aoyagi, Tomio Takeuchi, Masa Hamada, Yoshiro Okami, “Biologically active substance, bestatin, and production thereof.” U.S. Patent US4052449, issued October 04, 1977.

US4052449
General References
  1. Scornik OA, Botbol V: Bestatin as an experimental tool in mammals. Curr Drug Metab. 2001 Mar;2(1):67-85. [PubMed:11465152 ]
  2. Yoneda J, Saiki I, Fujii H, Abe F, Kojima Y, Azuma I: Inhibition of tumor invasion and extracellular matrix degradation by ubenimex (bestatin). Clin Exp Metastasis. 1992 Jan;10(1):49-59. [PubMed:1733647 ]
  3. Bauvois B, Dauzonne D: Aminopeptidase-N/CD13 (EC 3.4.11.2) inhibitors: chemistry, biological evaluations, and therapeutic prospects. Med Res Rev. 2006 Jan;26(1):88-130. [PubMed:16216010 ]
  4. Wickstrom M, Larsson R, Nygren P, Gullbo J: Aminopeptidase N (CD13) as a target for cancer chemotherapy. Cancer Sci. 2011 Mar;102(3):501-8. doi: 10.1111/j.1349-7006.2010.01826.x. Epub 2011 Jan 30. [PubMed:21205077 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.6845
Blood Brain Barrier-0.7474
Caco-2 permeable-0.815
P-glycoprotein substrateNon-substrate0.5343
P-glycoprotein inhibitor INon-inhibitor0.9033
P-glycoprotein inhibitor IINon-inhibitor0.9167
Renal organic cation transporterNon-inhibitor0.9677
CYP450 2C9 substrateNon-substrate0.7943
CYP450 2D6 substrateNon-substrate0.8017
CYP450 3A4 substrateNon-substrate0.5757
CYP450 1A2 substrateNon-inhibitor0.9068
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.947
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8869
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9469
Ames testNon AMES toxic0.8067
CarcinogenicityNon-carcinogens0.8884
BiodegradationNot ready biodegradable0.528
Rat acute toxicity1.8987 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9992
hERG inhibition (predictor II)Non-inhibitor0.9606
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.841 mg/mLALOGPS
logP-1.7ALOGPS
logP-0.46ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)3.77ChemAxon
pKa (Strongest Basic)9.54ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area116.14 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity82.57 m3·mol-1ChemAxon
Polarizability32.97 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as hybrid peptides. These are compounds containing at least two different types of amino acids (alpha, beta, gamma, delta) linked to each other through a peptide bond.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassAmino acids, peptides, and analogues
Direct ParentHybrid peptides
Alternative Parents
Substituents
  • Hybrid peptide
  • N-acyl-aliphatic-alpha amino acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Beta amino acid or derivatives
  • N-acyl-l-alpha-amino acid
  • Amphetamine or derivatives
  • Alpha-amino acid or derivatives
  • N-substituted-alpha-amino acid
  • Aralkylamine
  • Amino fatty acid
  • Fatty acyl
  • Benzenoid
  • N-acyl-amine
  • Monosaccharide
  • Fatty amide
  • Monocyclic benzene moiety
  • Secondary carboxylic acid amide
  • Secondary alcohol
  • Carboxamide group
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Primary aliphatic amine
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External DescriptorsNot Available

Targets

Kind
Protein
Organism
Vibrio proteolyticus
Pharmacological action
unknown
General Function:
Metal ion binding
Specific Function:
Not Available
Gene Name:
Not Available
Uniprot ID:
Q01693
Molecular Weight:
54231.585 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Ocheltree SM, Shen H, Hu Y, Xiang J, Keep RF, Smith DE: Mechanisms of cefadroxil uptake in the choroid plexus: studies in wild-type and PEPT2 knockout mice. J Pharmacol Exp Ther. 2004 Feb;308(2):462-7. Epub 2003 Nov 4. [PubMed:14600253 ]
  4. Saito H, Terada T, Okuda M, Sasaki S, Inui K: Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim Biophys Acta. 1996 Apr 26;1280(2):173-7. [PubMed:8639691 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Zinc ion binding
Specific Function:
Epoxide hydrolase that catalyzes the final step in the biosynthesis of the proinflammatory mediator leukotriene B4. Has also aminopeptidase activity.
Gene Name:
LTA4H
Uniprot ID:
P09960
Molecular Weight:
69284.64 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular Weight:
78805.265 Da
References
  1. Terada T, Sawada K, Irie M, Saito H, Hashimoto Y, Inui K: Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflugers Arch. 2000 Sep;440(5):679-84. [PubMed:11007306 ]
  2. Saito H, Okuda M, Terada T, Sasaki S, Inui K: Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney. J Pharmacol Exp Ther. 1995 Dec;275(3):1631-7. [PubMed:8531138 ]
  3. Terada T, Saito H, Mukai M, Inui K: Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J Pharmacol Exp Ther. 1997 Jun;281(3):1415-21. [PubMed:9190878 ]
  4. Sala-Rabanal M, Loo DD, Hirayama BA, Turk E, Wright EM: Molecular interactions between dipeptides, drugs and the human intestinal H+ -oligopeptide cotransporter hPEPT1. J Physiol. 2006 Jul 1;574(Pt 1):149-66. Epub 2006 Apr 20. [PubMed:16627568 ]
  5. Saito H, Terada T, Okuda M, Sasaki S, Inui K: Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim Biophys Acta. 1996 Apr 26;1280(2):173-7. [PubMed:8639691 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrateinhibitor
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. Terada T, Sawada K, Irie M, Saito H, Hashimoto Y, Inui K: Structural requirements for determining the substrate affinity of peptide transporters PEPT1 and PEPT2. Pflugers Arch. 2000 Sep;440(5):679-84. [PubMed:11007306 ]
  2. Saito H, Terada T, Okuda M, Sasaki S, Inui K: Molecular cloning and tissue distribution of rat peptide transporter PEPT2. Biochim Biophys Acta. 1996 Apr 26;1280(2):173-7. [PubMed:8639691 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23