Ubenimex

Identification

Generic Name
Ubenimex
DrugBank Accession Number
DB03424
Background

Ubenimex (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.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 308.3728
Monoisotopic: 308.173607266
Chemical Formula
C16H24N2O4
Synonyms
  • Ubenimex
  • Ubenimexum

Pharmacology

Indication

An adjuvant therapy used for acute and chronic myelonous leukemia, lung cancer and nasopharyngeal cancer. It is also used to treat hypercholesterolaemia.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Contraindications & Blackbox Warnings
Prevent Adverse Drug Events Today
Tap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events with our Clinical API
Learn more
Pharmacodynamics

Not Available

Mechanism of action
TargetActionsOrganism
UBacterial leucyl aminopeptidaseNot AvailableVibrio proteolyticus
ULeukotriene A-4 hydrolaseNot AvailableHumans
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!
See the data
Improve decision support & research outcomes with our structured adverse effects data.
See a data sample
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolThe risk or severity of bleeding can be increased when Ubenimex is combined with Acenocoumarol.
AmbroxolThe risk or severity of methemoglobinemia can be increased when Ubenimex is combined with Ambroxol.
ArticaineThe risk or severity of methemoglobinemia can be increased when Ubenimex is combined with Articaine.
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Ubenimex.
BenzocaineThe risk or severity of methemoglobinemia can be increased when Ubenimex is combined with Benzocaine.
Food Interactions
Not Available

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Product Ingredients
IngredientUNIICASInChI Key
Ubenimex hydrochlorideBY7Y2JX7NQ65391-42-6XGDFITZJGKUSDK-UDYGKFQRSA-N
International/Other Brands
Bestatin (Nippon Kayaku, Japan)

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Peptidomimetics
Sub Class
Hybrid peptides
Direct Parent
Hybrid peptides
Alternative Parents
Leucine and derivatives / N-acyl-L-alpha-amino acids / Beta amino acids and derivatives / Amphetamines and derivatives / Aralkylamines / N-acyl amines / Monosaccharides / Secondary carboxylic acid amides / Secondary alcohols / Amino acids
show 7 more
Substituents
Alcohol / Alpha-amino acid or derivatives / Amine / Amino acid / Amino acid or derivatives / Amphetamine or derivatives / Aralkylamine / Aromatic homomonocyclic compound / Benzenoid / Beta amino acid or derivatives
show 26 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
I0J33N5627
CAS number
58970-76-6
InChI Key
VGGGPCQERPFHOB-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-2-hydroxy-4-phenylbutanamido]-4-methylpentanoic acid
SMILES
CC(C)C[C@H](NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1)C(O)=O

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
PubChem Compound
72172
PubChem Substance
46505598
ChemSpider
65145
BindingDB
50367209
ChEMBL
CHEMBL29292
ZINC
ZINC000001542895
PDBe Ligand
BES
Wikipedia
Ubenimex
PDB Entries
1gw6 / 1hs6 / 1txr / 1xry / 2dqm / 2ek9 / 2hpt / 2xq0 / 2yd0 / 2zof
show 16 more

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3CompletedBasic ScienceIschemic Stroke1
3CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
2CompletedTreatmentLymphedema1
2CompletedTreatmentPulmonary Arterial Hypertension (PAH)1
2TerminatedTreatmentPulmonary Arterial Hypertension (PAH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility1.29 mg/mLALOGPS
logP-1.2ALOGPS
logP-1.1Chemaxon
logS-2.4ALOGPS
pKa (Strongest Acidic)3.73Chemaxon
pKa (Strongest Basic)8.35Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area112.65 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity82.05 m3·mol-1Chemaxon
Polarizability33.09 Å3Chemaxon
Number of Rings1Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0fgo-5910000000-61e501b29e8f0b141016
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-000i-0139000000-68cc530f9654794b2c47
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ab9-2917000000-bfbc8526e18475632afb
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0139000000-68cc530f9654794b2c47
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0ab9-1819000000-90a828fa86b21c610820
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-08fr-3793000000-a4f93a6ea95c8a785107
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-001i-0912000000-7feeac45dab6b28da316
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-001l-6900000000-b23ef6248e8ef52aa4d3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0inc-4910000000-922d083e25fb6d19bfd7
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9400000000-c5e8fc02a80cf10f9da7
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0pbc-5900000000-aba7b1046568ecd5318c
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-175.45589
predicted
DeepCCS 1.0 (2019)
[M+H]+177.85146
predicted
DeepCCS 1.0 (2019)
[M+Na]+185.20471
predicted
DeepCCS 1.0 (2019)

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Kind
Protein
Organism
Vibrio proteolyticus
Pharmacological action
Unknown
General Function
Metal ion binding
Specific Function
Not Available
Gene Name
Not Available
Uniprot ID
Q01693
Uniprot Name
Bacterial leucyl aminopeptidase
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Details
2. Leukotriene A-4 hydrolase
Kind
Protein
Organism
Humans
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
Uniprot Name
Leukotriene A-4 hydrolase
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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Hydrolyzes a wide range of dipeptides. Implicated in the renal metabolism of glutathione and its conjugates. Converts leukotriene D4 to leukotriene E4; it may play an important role in the regulati...
Gene Name
DPEP1
Uniprot ID
P16444
Uniprot Name
Dipeptidase 1
Molecular Weight
45673.48 Da
References
  1. Campbell BJ, Di Shih Y, Forrester LJ, Zahler WL: Specificity and inhibition studies of human renal dipeptidase. Biochim Biophys Acta. 1988 Sep 21;956(2):110-8. doi: 10.1016/0167-4838(88)90256-7. [Article]

Transporters

Kind
Protein
Organism
Humans
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
Uniprot Name
Solute carrier family 15 member 1
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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Uniprot Name
Solute carrier family 15 member 2
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. [Article]
  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. [Article]

Drug created at June 13, 2005 13:24 / Updated at May 05, 2022 17:58