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

Structure

 

Show IUPAC/InChI/SMILES

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.





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