Pomalidomide-d5

Description

Pomalidomide-d₅ is intended for use as an internal standard for the quantification of pomalidomide by GC- or LC-MS. Pomalidomide is an analog of thalidomide that inhibits the E3 ligase protein cereblon (CRBN) with an IC₅₀ value of approximately 3 μM for the human recombinant CRBN-DNA damage binding protein-1 (CRBN-DDB1) complex. It inhibits autoubiquitination of CRBN in HEK293T cells expressing CRBN but not those expressing a thalidomide-binding defective CRBN mutation. It inhibits proliferation of U266 myeloma cells when used at concentrations ranging from 0.1 to 10 μM. Pomalidomide also has antiangiogenic and immunomodulatory effects against myeloma cells, modulating cell adhesion, decreasing production of key pro-survival cytokines, including TNF-α, and triggering the activation of caspase-8. Pomalidomide (3 mg/kg per day), in combination with dexamethasone, reduces tumor growth in a H929 R10-1 lenalidomide-resistant mouse xenograft model. Formulations containing pomalidomide have been used in the treatment of multiple myeloma.

Uses

Pomalidomide-d5 is the labeled analogue of Pomalidomide (P688200), a thalidomide derivative, a potent inhibitor of TNF-α production. It is an antiinflammatory and antitumor agent used in the treatment of multiple myeloma.

IC 50

Cereblon

References

[1] A LOPEZ-GIRONA. Cereblon is a direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide[J]. Leukemia, 2012, 26 11: 2326-2335. DOI: 10.1038/leu.2012.119
[2] YUAN XIAO ZHU  A K S  K Martin Kortuem. Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma.[J]. Leukemia & Lymphoma, 2013, 54 4: 683-687. DOI: 10.3109/10428194.2012.728597
[3] TAHIR LATIF. Thalidomide and its analogues in the treatment of Multiple Myeloma.[J]. Experimental Hematology & Oncology, 2012, 1 1: 27. DOI: 10.1186/2162-3619-1-27
[4] EMILY RYCHAK. Pomalidomide in combination with dexamethasone results in synergistic anti-tumour responses in pre-clinical models of lenalidomide-resistant multiple myeloma[J]. British Journal of Haematology, 2016, 172 6: 889-901. DOI: 10.1111/bjh.13905