MedKoo product information:

  Tosedostat

Tosedostat is a proprietary orally bioavailable inhibitor of the M1 family of aminopeptidases with potential antineoplastic activity. Tosedostat 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. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:    Chroma Therapeutics

1. Aminopeptidase inhibition by the novel agent CHR-2797 (tosedostat) for the therapy of acute myeloid leukemia By Jenkins, Christopher; Hewamana, Saman; Krige, David; Pepper, Chris; Burnett, Alan From Leukemia Research (2011), 35(5), 677-681.

2. Phase I/II clinical study of tosedostat, an inhibitor of aminopeptidases, in patients with acute myeloid leukemia and myelodysplasia By Loewenberg, Bob; Morgan, Gareth; Ossenkoppele, Gert I.; Burnett, Alan K.; Zachee, Pierre; Duehrsen, Ulrich; Dierickx, Daan; Mueller-Tidow, Carsten; Sonneveld, Pieter; Krug, Utz; et al From Journal of Clinical Oncology (2010), 28(28), 4333-4338.

3. A Phase Ib dose-escalation study to evaluate safety and tolerability of the addition of the aminopeptidase inhibitor tosedostat (CHR-2797) to paclitaxel in patients with advanced solid tumours By van Herpen, C. M. L.; Eskens, F. A. L. M.; de Jonge, M.; Desar, I.; Hooftman, L.; Bone, E. A.; Timmer-Bonte, J. N. H.; Verweij, J. From British Journal of Cancer (2010), 103(9), 1362-1368.

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7. Gene expression biomarkers of aminopeptidase inhibition in tumor-derived cell lines By Krige, David; Drummond, Alan Hastings From PCT Int. Appl. (2009), WO 2009098451 A2 20090813.

8. A First-in-Man Phase I and Pharmacokinetic Study on CHR-2797 (Tosedostat), an Inhibitor of M1 Aminopeptidases, in Patients with Advanced Solid Tumors By Reid, Alison H. M.; Protheroe, Andrew; Attard, Gerhardt; Hayward, Nikki; Vidal, Laura; Spicer, James; Shaw, Heather M.; Bone, Elizabeth A.; Carter, Joanne; Hooftman, Leon; et al From Clinical Cancer Research (2009), 15(15), 4978-4985.

9. Tosedostat: aminopeptidase inhibitor oncolytic By Owen, R. T.; Castaner, R.; Bolos, J. From Drugs of the Future (2009), 34(2), 115-118.

10. Aminopeptidase inhibition as a targeted treatment strategy in myeloma By Moore, Hannah E.; Davenport, Emma L.; Smith, Emma M.; Muralikrishnan, Srikanth; Dunlop, Alan S.; Walker, Brian A.; Krige, David; Drummond, Alan H.; Hooftman, Leon; Morgan, Gareth J.; et al From Molecular Cancer Therapeutics (2009), 8(4), 762-770.

11. Dosing schedules of leukotriene synthesis inhibitors for human therapy By Hermann, David J.; Hartman, Daniel L.; Van Ess, Peter James; Wang, Wenping From PCT Int. Appl. (2008), WO 2009002746 A1 20081231.

12. CHR-2797: An Antiproliferative Aminopeptidase Inhibitor that Leads to Amino Acid Deprivation in Human Leukemic Cells By Krige, David; Needham, Lindsey A.; Bawden, Lindsay J.; Flores, Nicolas; Farmer, Hannah; Miles, Lauren E. C.; Stone, Erica; Callaghan, Juliana; Chandler, Stephen; Clark, Vanessa L.; et al From Cancer Research (2008), 68(16), 6669-6679.

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17. Aminopeptidase N (CD13) as a target for cancer chemotherapy By Wickstrom Malin; Larsson Rolf; Nygren Peter; Gullbo Joachim From Cancer science (2011), 102(3), 501-8.