Tosedostat

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Generic Name
Tosedostat
DrugBank Accession Number
DB11781
Background

Tosedostat has been used in trials studying the treatment and supportive care of AML, Leukemia, Pancreas Cancer, Multiple Myeloma, and Pancreatic Cancer, among others.

Tosedostat is an inhibitor of the M1 family of aminopeptidases, in particular PuSA, and LTA4 hydrolase. It has demonstrated anti-tumour activity in a number of models of cancer, both as a single agent and in synergy with cytotoxic agents such as carboplatin and paclitaxel. It entered the clinical trial in patients with haematological malignancies.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 406.479
Monoisotopic: 406.210386694
Chemical Formula
C21H30N2O6
Synonyms
  • Tosedostat
External IDs
  • CHR 2797
  • CHR-2797

Pharmacology

Indication

Not Available

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Pharmacodynamics

Tosedostat has pleiotropic effects against a range of human tumor cell lines originating from diverse tumor types in vitro and in vivo.

Mechanism of action

Tosedostat is anti-proliferative agent which induces apoptosis in leukemic cell lines in vitro. The mechanism underlying these anti-cancer actions is unclear, particularly since normal cells are much less sensitive to the agents than transformed cells. It exerts potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro and shows selectivity for transformed over non-transformed cells. It inhibits a number of M1 aminopeptidase enzyme family members in vitro (eg puromycin-sensitive aminopeptidase (PSA), leukotriene A4 hydrolase (LTA4H)).

TargetActionsOrganism
UPuromycin-sensitive aminopeptidaseNot AvailableHumans
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
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as n-acyl-alpha amino acids and derivatives. These are compounds containing an alpha amino acid (or a derivative thereof) which bears an acyl group at its terminal nitrogen atom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
N-acyl-alpha amino acids and derivatives
Alternative Parents
Alpha amino acid esters / N-acyl amines / Monosaccharides / Benzene and substituted derivatives / Secondary carboxylic acid amides / Secondary alcohols / Hydroxamic acids / Carboxylic acid esters / Monocarboxylic acids and derivatives / Organopnictogen compounds
show 4 more
Substituents
Alcohol / Alpha-amino acid ester / Aromatic homomonocyclic compound / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid ester / Fatty acyl / Fatty amide / Hydrocarbon derivative
show 14 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
KZK563J2UW
CAS number
238750-77-1
InChI Key
FWFGIHPGRQZWIW-SQNIBIBYSA-N
InChI
InChI=1S/C21H30N2O6/c1-13(2)12-16(18(24)20(26)23-28)19(25)22-17(14-8-4-3-5-9-14)21(27)29-15-10-6-7-11-15/h3-5,8-9,13,15-18,24,28H,6-7,10-12H2,1-2H3,(H,22,25)(H,23,26)/t16-,17+,18+/m1/s1
IUPAC Name
cyclopentyl (2S)-2-[(2R,3S)-3-hydroxy-3-(hydroxycarbamoyl)-2-(2-methylpropyl)propanamido]-2-phenylacetate
SMILES
CC(C)C[C@H]([C@H](O)C(=O)NO)C(=O)N[C@H](C(=O)OC1CCCC1)C1=CC=CC=C1

References

General References
Not Available
PubChem Compound
15547703
PubChem Substance
347828131
ChemSpider
24606030
ChEBI
95044
ChEMBL
CHEMBL2103847
ZINC
ZINC000013914293

Clinical Trials

Clinical Trials

Pharmacoeconomics

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

Properties

State
Not Available
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.092 mg/mLALOGPS
logP1.9ALOGPS
logP2.13Chemaxon
logS-3.6ALOGPS
pKa (Strongest Acidic)8.61Chemaxon
pKa (Strongest Basic)-2.2Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count4Chemaxon
Polar Surface Area124.96 Å2Chemaxon
Rotatable Bond Count10Chemaxon
Refractivity105.13 m3·mol-1Chemaxon
Polarizability42.88 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-05dr-0159000000-dc4f27b5cdd0944d1597
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-004i-0093000000-25763fe55e5b231c1d8c
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0059-2191000000-4af891797773688a22e6
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-052f-9140000000-08607745703a3dc30da4
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0udi-2390000000-4ad2c6d1b909d255dc52
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0k97-9660000000-de8675178e05a5f8fb93
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]-205.6176375
predicted
DarkChem Lite v0.1.0
[M-H]-195.5195
predicted
DeepCCS 1.0 (2019)
[M+H]+206.3541375
predicted
DarkChem Lite v0.1.0
[M+H]+197.91507
predicted
DeepCCS 1.0 (2019)
[M+Na]+206.3090375
predicted
DarkChem Lite v0.1.0
[M+Na]+203.82759
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Aminopeptidase with broad substrate specificity for several peptides. Involved in proteolytic events essential for cell growth and viability. May act as regulator of neuropeptide activity. Plays a ...
Gene Name
NPEPPS
Uniprot ID
P55786
Uniprot Name
Puromycin-sensitive aminopeptidase
Molecular Weight
103275.36 Da
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

Drug created at October 20, 2016 20:47 / Updated at January 14, 2023 19:03