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19171-19-8 molecular structure
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4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione

ChemBase ID: 72747
Molecular Formular: C13H11N3O4
Molecular Mass: 273.24414
Monoisotopic Mass: 273.07495585
SMILES and InChIs

SMILES:
c1ccc2c(c1N)C(=O)N(C2=O)C1C(=O)NC(=O)CC1
Canonical SMILES:
O=C1CCC(C(=O)N1)N1C(=O)c2c(C1=O)c(N)ccc2
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)
InChIKey:
UVSMNLNDYGZFPF-UHFFFAOYSA-N

Cite this record

CBID:72747 http://www.chembase.cn/molecule-72747.html

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NAMES AND DATABASE IDS

NAMES AND DATABASE IDS

Names Database IDs
IUPAC name
4-amino-2-(2,6-dioxopiperidin-3-yl)-2,3-dihydro-1H-isoindole-1,3-dione
IUPAC Traditional name
pomalidomide
Synonyms
4-Amino-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione
1,3-dioxo-2-(2,6-dioxopiperidin-3-yl)-4-aminoisoindoline
3-amino-N-(2,6-dioxo-3-piperidyl)phthalamide
4-Amino-2-(2,6-dioxo-3-piperidinyl)-1H-isoindole-1,3(2H)-dione
IMiD 3
Pomalidomide
CC-4047
Actimid
Pomalidomide
CAS Number
19171-19-8
MDL Number
MFCD12756407
PubChem SID
162037668
PubChem CID
134780

DATA SOURCES

DATA SOURCES

All Sources Commercial Sources Non-commercial Sources
Data Source Data ID
PubChem 134780 external link

CALCULATED PROPERTIES

CALCULATED PROPERTIES

JChem
Acid pKa 11.593278  H Acceptors
H Donor LogD (pH = 5.5) -0.16326816 
LogD (pH = 7.4) -0.16324674  Log P -0.1632186 
Molar Refractivity 69.0252 cm3 Polarizability 25.184988 Å3
Polar Surface Area 109.57 Å2 Rotatable Bonds
Lipinski's Rule of Five true 

PROPERTIES

PROPERTIES

Physical Property Safety Information Pharmacology Properties Product Information Bioassay(PubChem)
Solubility
DMSO: ≥14 mg/mL expand Show data source
Apperance
yellow powder expand Show data source
Storage Condition
-20°C expand Show data source
MSDS Link
Download expand Show data source
German water hazard class
3 expand Show data source
Storage Temperature
2-8°C expand Show data source
Target
COX expand Show data source
TNF-α expand Show data source
Purity
≥98% (HPLC) expand Show data source
95+% expand Show data source
Salt Data
Free Base expand Show data source
Empirical Formula (Hill Notation)
C13H11N3O4 expand Show data source

DETAILS

DETAILS

Selleck Chemicals Selleck Chemicals Sigma Aldrich Sigma Aldrich
Selleck Chemicals - S1567 external link
Research Area
Description Small cell lung cancer,Sarcoma,Myelofibrosis
Biological Activity
Description Pomalidomide inhibits LPS-induced TNF-α release with IC50 of 13 nM.
Targets TNF-α
IC50 13 nM [1]
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. [1] Pomalidomide inhibits the growth of T regulatory cells which is stimulated by IL-2 with an IC50 of ~1 μM. [2] 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. [3] 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. [4]
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. [4]
Clinical Trials A Phase I study to evaluate the safety, tolerability, and pharmacokinetics of Pomalidomide (CC-4047) following multiple daily doses in healthy male subjects has been completed.
Features Pomalidomide is a derivative of thalidomide and up to 10,000 times more potent than thalidomide.
Protocol
Kinase Assay [1]
Inhibition of TNF-α synthesis 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 inhibits TNF- production by 50% (IC50) is calculated by nonlinear regression analysis. The human whole blood TNF- inhibition assay is run in a similar fashion to the PBMC assay except that heparinized fresh human whole blood is plated directly into microtiter plates.
Cell Assay [4]
Cell Lines Raji, SU-DHL-4 and SU-DHL-10 cell lines
Concentrations Dissolved in DMSO, final concentrations 2.5-40 μg/mL
Incubation Time 24 or 48 hours
Methods For assessment of cell apoptosis, Lymphoma cell lines are exposed to Pomalidomide (5 μg/mL) for 24 hours or 48 hours. The cells are stained with FITC-labeled Annexin V and propidium iodine. Cell apoptosis is analyzed by multicolor flow cytometric analysis using a fluorescence-activated cell sorter/FACStar Plus flow cytometer. Cells are scored as apoptotic if they are Annexin V–positive and propidium iodine–negative/positive (early and late apoptosis, respectively). For determination of cell proliferation, the Lymphoma cell lines are exposed to Pomalidomide (2.5, 5, 10, 20, and 40 μg/mL) for 24 hours or 48 hours. 1 μCi per well (96-well plate) of [3H]-thymidine is added and cells are incubated for another 18 hours. Cells are then harvested using the Harvest system into the 96-well glass filters and [3H]-thymidine uptake is measured using an automated scintillation counter.
Animal Study [4]
Animal Models Disseminated lymphoma-bearing SCID mice
Formulation Dissolved in DMSO to make a 10 mg/mL stock solution and diluted to a final concentration of 1 mg/mL in sterile 0.9% normal saline.
Doses 0.5 mg/kg
Administration Injection i.p.
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.
Sigma Aldrich - P0018 external link
Biochem/physiol Actions
Pomalidomide is a second generation immunomodulator, TNF-α inhibitor, and thalidomide analog.

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