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Pomalidomide

Catalog No. T2384 CAS 19171-19-8

Synonyms: CC-4047

Pomalidomide (CC-4047) inhibits TNF-α release in LPS stimulated human PBMCs (IC50: 13 nM). It is an anti-angiogenic agent and an immunomodulator.

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Pomalidomide, CAS 19171-19-8

Pack Size	Availability	Price/USD
10 mg	In stock	$ 52.00
50 mg	In stock	$ 78.00
100 mg	In stock	$ 101.00
200 mg	In stock	$ 111.00
500 mg	In stock	$ 129.00
1 g	In stock	$ 168.00
1 mL * 10 mM (in DMSO)	In stock	$ 57.00

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Purity: 100%

Purity: 98.98%

Purity: 98.8%

Purity: 98.4%

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Description	Pomalidomide (CC-4047) inhibits TNF-α release in LPS stimulated human PBMCs (IC50: 13 nM). It is an anti-angiogenic agent and an immunomodulator.
Targets&IC50	TNF-α:13 nM (PBMCs)
In vitro	Pomalidomide (CC-4047) was significant inhibition against TNFα in Human PBMC cell with an IC50 of 13 nM [1]. Pomalidomide inhibits IL-2-mediated generation of FOXP3 positive CTLA-4 positive CD25high CD4+ T regulatory cells from PBMCs by up to 50% [2]. Exposure of lymphoma cells to CC-4047 resulted in a lesser degree of growth inhibition. Induction of apoptosis was shown in 10% to 26% of lymphoma cells 24 hours following exposure to CC-4047 [3].
In vivo	In vivo studies in severe combined immunodeficient mice showed synergistic activity between CC-4047 plus rituximab. Animals treated with the CC-4047/rituximab combination had a median survival of 74 days [3]. POM has desirable pharmacokinetic properties in the rat. It had relatively slow clearance (12.3 mL/min/kg), a reasonable volume of distribution (1.75 L/kg), and an acceptable bioavailability (47.4%). Following a 50 mg/kg PO administration of POM to rats, unbound concentrations in blood reached a Cmax value of 1100 ± 82 ng/mL at 4.6 ± 2.4 hours, with a concomitant AUC(0?10) value of 6800 ± 2000 ng·hr/mL [4].
Kinase Assay	TNF-α inhibitory activity is measured in lipopolysacharide (LPS) stimulated PBMC. Pomalidomide is added to human PBMCs 1 hour prior to the addition of LPS (1 μg/mL) and incubation continued for an additional 18-20 hours. Supernatants are then harvested, and the concentration of TNF-α in the supernatants is determined by ELISA. The concentration of Pomalidomide that IC50 is calculated by nonlinear regression analysis [1].
Cell Research	In vitro effects of either CC-5013 or CC-4047 as single agent or in combination with rituximab were evaluated by flow cytometric analysis. Lymphoma cell lines (1 × 10^6 cells) were exposed to either CC-5013 (5 μg/mL), CC-4047 (5 μg/mL), or vehicle control (DMRIE-C, 0.01%) alone or in combination with rituximab at a final concentration of 10 μg/mL. Following a period of incubation of 24 or 48 hours, apoptosis was assessed by staining-treated cells with FITC-labeled Annexin V and propidium iodine. All samples were analyzed by multicolor flow cytometric analysis using a fluorescence-activated cell sorter/FACStar Plus flow cytometer. Cells were scored as apoptotic if they were Annexin V–positive and propidium iodine–negative/positive (early and late apoptosis, respectively) [2].
Animal Research	These studies were carried out using a disseminated lymphoma-bearing SCID mouse xenograft model. Raji cells were harvested from confluent cultures and only suspensions with >90% viable cells were used for animal inoculation. Subsequently, on day 0, SCID mice received 1 ×10^6 Raji cells via i.v. Untreated SCID mice inoculated by i.v. injection develop symptomatic central nervous system, pulmonary, and liver metastasis that result in death from massive tumor burden and central nervous system involvement after 17 to 21 days after inoculation. A second lymphoma mouse model was used to address the significance of NK cell expansion in the biological interactions observed between rituximab and IMiDs. The second mouse lymphoma xenograft consisted of SCID mice depleted of NK cells bearing Raji cells implanted via tail vein injection as described above [2].

Synonyms	CC-4047
Molecular Weight	273.24
Formula	C13H11N3O4
CAS No.	19171-19-8

Storage

Powder: -20°C for 3 years | In solvent: -80°C for 1 year

Solubility Information

H2O: < 1 mg/mL (insoluble or slightly soluble)

DMSO: 54 mg/mL (197.63 mM)

Ethanol: < 1 mg/mL (insoluble or slightly soluble)

References and Literature

1. Muller GW, et al. Amino-substituted thalidomide analogs: potent inhibitors of TNF-alpha production. Bioorg Med Chem Lett. 1999 Jun 7;9(11):1625-30. 2. Hernandez-Ilizaliturri FJ1, et al. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005 Aug 15;11(16):5984-92. 3. Galustian C, et al. The anti-cancer agents lenalidomide and pomalidomide inhibit the proliferation and function of T regulatory cells. Cancer Immunol Immunother. 2009 Jul;58(7):1033-45. 4. Li Z, et al. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models. PLoS One. 2013 Aug 5;8(8):e71754.

Citations

1. Durbin A D, Wang T, Wimalasena V K, et al. EP300 Selectively Controls the Enhancer Landscape of MYCN-Amplified NeuroblastomaEP300 Controls Enhancers and MYCN in Neuroblastoma. Cancer Discovery. 2022-12 (3) P730

Related compound libraries

This product is contained In the following compound libraries：

Anti-Cancer Drug Library Drug Repurposing Compound Library EMA Approved Drug Library Anti-Cancer Clinical Compound Library Anti-Cancer Approved Drug Library Anti-Cancer Active Compound Library Drug-Fragment Library HIF-1 Signaling Pathway Compound Library Pediatric Drug Library Transcription Factor-Targeted Compound Library

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Keywords

Pomalidomide 19171-19-8 Apoptosis PROTAC TNF Ligand for E3 Ligase Molecular Glues Ligands for E3 Ligase CC-4047 inhibit CC4047 CC 4047 Inhibitor E3 ligase-recruiting Moiety inhibitor

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