Tosedostat
DRACPC ID DRACPC0047
Active Ingredients Tosedostat
Description A proprietary orally bioavailable inhibitor of the M1 family of aminopeptidases with potential antineoplastic activity. Aminopeptidase inhibitor CHR-2797 is converted intracellularly into a poorly membrane-permeable active metabolite (CHR-79888) which inhibits the M1 family of aminopeptidases, particularly puromycin-sensitive aminopeptidase (PuSA), and leukotriene A4 (LTA4) hydrolase; inhibition of these aminopeptidases in tumor cells may result in amino acid deprivation, inhibition of protein synthesis due to a decrease in the intracellular free amino acid pool, an increase in the level of the proapoptotic protein Noxa, and cell death. Noxa is a member of the BH3 (Bcl-2 homology 3)-only subgroup of the proapoptotic Bcl-2 (B-cell CLL/lymphoma 2) protein family.
Synonyms Aminopeptidase inhibitor CHR-2797; CHR-2797; Cyclopentyl (2S)-2-{(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4- methylpentanamido}-2-phenylacetate; Tosedostat
Type Small Molecule
Disease AML, Leukemia, Pancreas Cancer, Multiple Myeloma, Pancreatic Cancer
Classification
Aminopeptidase inhibitor Amino acid and derivative
Structure Information
Molecular Formula C21H30N2O6
Molecular Weight 406.5
Active Sequence Not available
Sequence Length Not available
Modification Not available
IUPAC Name cyclopentyl (2S)-2-[[(2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoyl]amino]-2-phenylacetate
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
InChI_Key FWFGIHPGRQZWIW-SQNIBIBYSA-N
SMILES O=C(OC1CCCC1)[C@@H](NC([C@@H]([C@H](O)C(NO)=O)CC(C)C)=O)C2=CC=CC=C2
External Codes
PubChem CID 15547703
DrugBank Accession Number DB11781
NCI Thesaurus Code C70650
UNII KZK563J2UW GSRS
CAS 238750-77-1
Drug approval
Drug indication
Tosedostat has been used in trials studying the treatment and supportive care of AML, Leukemia, Pancreas Cancer, Multiple Myeloma, and Pancreatic Cancer, among others.
The drug is not approved.
| ClinicalTrials.gov Identifier | Title | Condition or disease | Phase | Purpose |
|---|---|---|---|---|
| NCT00780598 | The OPAL Study: A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of Tosedostat (CHR-2797) in Elderly Subjects With Treatment Refractory or Relapsed Acute Myeloid Leukemia | Acute Myeloid Leukemia; AML | Phase 2 | Treatment |
| NCT00689000 | A Phase I-II Study to Evaluate the Safety, Tolerability and Anti-Disease Activity of the Aminopeptidase Inhibitor, CHR-2797, in Elderly and/or Treatment Refractory Patients With Acute Myeloid Leukemia or Multiple Myeloma | Acute Myeloid Leukemia; Myelodysplastic Syndrome; Multiple Myeloma | Phase 1/2 | Treatment |
| NCT02452346 | Phase II Clinical Study of the Clinical Efficacy and Safety of Tosedostat in Atients With Myelodysplastic Syndromes (MDS) After Failure of Hypomethylating Agent-Based Therapy | Myelodysplastic Syndrome | Phase 2 | Treatment |
| NCT01180426 | The TOPAZ Study: A Long-Term Extension Study in Elderly Subjects With Relapsed/Refractory Acute Myeloid Leukemia to Allow Continued Therapy With Tosedostat | Acute Myeloid Leukemia | Phase 3 | Treatment |
| NCT00737555 | A Phase 1b Dose-escalation Study to Evaluate the Safety and Tolerability of the Addition of the Aminopeptidase Inhibitor CHR-2797 to Paclitaxel in Patients With Advanced or Refractory Tumours | Solid Tumor | Phase 1 | Treatment |
More clinical information is obtained from ClinicalTrials.gov.
