Pomalidomide

Pomalidomide, also known as CC4047, is an orally bioavailable derivative of thalidomide with potential immunomodulating, antiangiogenic and antineoplastic activities. Although its exact mechanism of action has yet to be fully elucidated, pomalidomide appears to inhibit TNF-alpha production, enhance the activity of T cells and natural killer (NK) cells and enhance antibody-dependent cellular cytotoxicity (ADCC). Pomalidomide was approved on February 8, 2013 as a treatment for relapsed and refractory multiple myeloma.

Product information

CAS Number: 19171-19-8

Molecular Weight: 273.24

Formula: C13H11N3O4

Synonym:

CC-4047

Pomalyst

Chemical Name: 4-amino-2-(2, 6-dioxopiperidin-3-yl)isoindoline-1, 3-dione

Smiles: NC1=CC=CC2=C1C(=O)N(C1CCC(=O)NC1=O)C2=O

InChiKey: UVSMNLNDYGZFPF-UHFFFAOYSA-N

InChi: InChI=1S/C13H11N3O4/c14-7-3-1-2-6-10(7)13(20)16(12(6)19)8-4-5-9(17)15-11(8)18/h1-3,8H,4-5,14H2,(H,15,17,18)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 54 mg/mL(197.62 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Pomalidomide inhibits lipopolysaccharide (LPS) stimulated TNF-alpha release in human PBMC and in human whole blood with IC50 values of 13 nM and 25 nM, respectively. Pomalidomide inhibits the growth of T regulatory cells which is stimulated by IL-2 with an IC50 of ~1 μM. Treatment with Pomalidomide (6.4 nM-10 μM) increases the production of IL-2 in human peripheral blood T cells, and is slightly more potent in the CD4+ subset than in the CD8+ subset. Pomalidomide is significantly more potent than CC-5013 at elevating IL-2, IL-5, and IL-10 levels, but only slightly more potent than CC-5013 at elevating IFN-γ levels. Pomalidomide enhances SEE and Raji cells induced AP-1 transcriptional activity in Jurkat cells in a dose-dependent manner, with a maximal enhancement of 4-fold at 1 μM. Exposure of Raji cells to various concentrations of Pomalidomide (2.5-40 μg/mL) for 48 hours leads to a significant decrease in cell proliferation and DNA synthesis. There is a reduction of ~40% compared to vehicle-treated controls.

In Vivo:

Pomalidomide enhances the antitumor effect of rituximab against B-cell lymphomas in severe combined immunodeficient mice. Administration of Pomalidomide in combination with rituximab, gives the mice a median survival period of 74 days compared with 58 days of CC5013/rituximab treatment and 45 days of rituximab nonotherapy. The synergistic effect of Pomalidomide and rituximab can be completely abrogated by depletion of NK cells, supporting the proposal that NK cell expansion is one mechanism by which Pomalidomide may augment rituximab antitumor activity.

References:

1. Muller GW, et al. Bioorg Med Chem Lett, 1999, 9(11), 1625-1630.
2. Galustian C, et al. Cancer Immunol Immunother, 2009, 58(7), 1033-1045.
3. Schafer PH, et al. J Pharmacol Exp Ther, 2003, 305(3), 1222-1232.
4. Hernandez-Ilizaliturri FJ, et al. Clin Cancer Res, 2005, 11(16), 5984-5992.
5. Jing Lu, et al. Chem Biol . 2015 Jun 18;22(6):755-63.

Products are for research use only. Not for human use.