Chemical Properties
Yellow Solid
Usage
Pomalidomide inhibits LPS-induced TNF-α release with IC50 of 13 nM
Usage
Pomalidomide is a second generation immunomodulator, TNF-α inhibitor, and thalidomide analog. An inhibitor of LPS-induced TNFαrelease.
Usage
Pomalidomide is a thalidomide derivative, a potent inhibitor of TNF-α production. It is an antiinflammatory and antitumor agent used in the treatment of multiple myeloma.
Originator
Celgene Corporation (United States)
Uses
Pomalidomide inhibits LPS-induced TNF-α release with IC50 of 13 nM
Uses
Pomalidomide is a second generation immunomodulator, TNF-α inhibitor, and thalidomide analog. An inhibitor of LPS-induced TNFαrelease.
Uses
Pomalidomide is a thalidomide derivative, a potent inhibitor of TNF-α production. It is an antiinflammatory and antitumor agent used in the treatment of multiple myeloma.
Definition
ChEBI: An aromatic amine that is thalidomide substituted at position 4 on the isoindole ring system by an amino group. Used for the treatment of multiple myeloma in patients who failed to respond to previous therapies.
Biochem/physiol Actions
Pomalidomide is an effective fetal hemoglobin (HbF) inducer that downregulates the key γ-globin repressors, SRY-box transcription factor 6 (SOX6), and BAF chromatin remodeling complex subunit (BCL11A).
Clinical Use
Treatment of multiple myeloma
Synthesis
First, condensation of commercially available 3-nitrophthalic
anhydride (133) and L-glutamine in warm DMF gave nitrophthalimide
134. Although the authors from Celgene do not
explicitly describe the racemization of the stereocenter derived
from L-glutamine, scrambling of the stereocenter has been
reported during this step under neutral conditions at elevated
temperatures. Next, hydrogenative reduction of the nitro group
furnished the anilinophthalimide 135, and this was followed by
treatment with CDI in refluxing acetonitrile to secure the piperidone
dione and ultimately furnish pomalidomide (XVIII) as the
racemate in 87% overall yield from 134.
Drug interactions
Potentially hazardous interactions with other drugs
Antidepressants: concentration increased by
fluvoxamine.
Metabolism
Mainly metabolised in the liver by the cytochrome P450
isoenzymes CYP1A2 and CYP3A4, with CYP2C19 and
CYP2D6 playing a minor role.
Following a single oral administration of
[14C]-pomalidomide (2 mg) to healthy subjects,
approximately 73% and 15% of the radioactive dose
was eliminated in urine and faeces, respectively, with
approximately 2% and 8% of the dosed radiocarbon
eliminated as pomalidomide in urine and faeces.
References
1) Lopez-Girona?et al.?(2012),?Cereblon is direct protein target for immunomodulatory and antiproliferative activities of lenalidomide and pomalidomide; Leukemia,?26?2326
2) Zhu?et al.?(2013),?Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma; Leukemia Lymphoma,?54?683
3) Donovan?et al.?(2018),?Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome; Elife,?7?e38430
4) Winter?et al.?(2015),?DRUG DEVELOPMENT. Phthalimide conjunction as a strategy for in vivo target protein degradation; Science,?348?1376
5) Lohbeck and Miller (2016),?Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development; Bioorg. Med. Chem. Lett.,?26?5260
