Tosedostat
Explore a selection of our essential drug information below, or:
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
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- 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)).
Target Actions Organism APuromycin-sensitive aminopeptidase inhibitorHumans ULeukotriene A-4 hydrolase Not Available Humans - 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 outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- External Links
- PubChem Compound
- 15547703
- PubChem Substance
- 347828131
- ChemSpider
- 24606030
- ChEBI
- 95044
- ChEMBL
- CHEMBL2103847
- ZINC
- ZINC000013914293
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data2 Completed Treatment Acute Myeloid Leukemia 1 somestatus stop reason just information to hide 2 Completed Treatment Acute Myeloid Leukemia With Multilineage Dysplasia / Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities / Adult Acute Myeloid Leukemia With Del(5q) / Adult Acute Myeloid Leukemia With T(15;17)(q22;q12) / Previously treated Myelodysplastic Syndromes (MDS) / Primary Myelodysplastic Syndromes (MDS) / Secondary Acute Myeloid Leukemia (Secondary AML, sAML) / Secondary Myelodysplastic Syndromes / Untreated Adult Acute Myeloid Leukemia 1 somestatus stop reason just information to hide 2 Completed Treatment Myelodysplastic Syndrome 1 somestatus stop reason just information to hide 2 Unknown Status Treatment Acute Myeloid Leukemia 1 somestatus stop reason just information to hide 1 Completed Basic Science Healthy Volunteers (HV) 1 somestatus stop reason just information to hide
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
Property Value Source Water Solubility 0.092 mg/mL ALOGPS logP 1.9 ALOGPS logP 2.13 Chemaxon logS -3.6 ALOGPS pKa (Strongest Acidic) 8.61 Chemaxon pKa (Strongest Basic) -2.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 124.96 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 105.13 m3·mol-1 Chemaxon Polarizability 42.88 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-05dr-0159000000-dc4f27b5cdd0944d1597 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-0093000000-25763fe55e5b231c1d8c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0059-2191000000-4af891797773688a22e6 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-052f-9140000000-08607745703a3dc30da4 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-2390000000-4ad2c6d1b909d255dc52 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0k97-9660000000-de8675178e05a5f8fb93 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 205.6176375 predictedDarkChem Lite v0.1.0 [M-H]- 195.5195 predictedDeepCCS 1.0 (2019) [M+H]+ 206.3541375 predictedDarkChem Lite v0.1.0 [M+H]+ 197.91507 predictedDeepCCS 1.0 (2019) [M+Na]+ 206.3090375 predictedDarkChem Lite v0.1.0 [M+Na]+ 203.82759 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General 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 role in the antigen-processing pathway for MHC class I molecules. Involved in the N-terminal trimming of cytotoxic T-cell epitope precursors. Digests the poly-Q peptides found in many cellular proteins. Digests tau from normal brain more efficiently than tau from Alzheimer disease brain
- Specific Function
- aminopeptidase activity
- Gene Name
- NPEPPS
- Uniprot ID
- P55786
- Uniprot Name
- Puromycin-sensitive aminopeptidase
- Molecular Weight
- 103275.36 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Bifunctional zinc metalloenzyme that comprises both epoxide hydrolase (EH) and aminopeptidase activities. Acts as an epoxide hydrolase to catalyze the conversion of LTA4 to the pro-inflammatory mediator leukotriene B4 (LTB4) (PubMed:11917124, PubMed:12207002, PubMed:15078870, PubMed:18804029, PubMed:1897988, PubMed:1975494, PubMed:2244921). Has also aminopeptidase activity, with high affinity for N-terminal arginines of various synthetic tripeptides (PubMed:18804029, PubMed:20813919). In addition to its pro-inflammatory EH activity, may also counteract inflammation by its aminopeptidase activity, which inactivates by cleavage another neutrophil attractant, the tripeptide Pro-Gly-Pro (PGP), a bioactive fragment of collagen generated by the action of matrix metalloproteinase-9 (MMP9) and prolylendopeptidase (PREPL) (PubMed:20813919, PubMed:24591641). Involved also in the biosynthesis of resolvin E1 and 18S-resolvin E1 from eicosapentaenoic acid, two lipid mediators that show potent anti-inflammatory and pro-resolving actions (PubMed:21206090)
- Specific Function
- 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 August 26, 2024 19:23