Pomalidomide

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Sicherheit

  P201：Vor Gebrauch besondere Anweisungen einholen.

  P202：Vor Gebrauch alle Sicherheitshinweise lesen und verstehen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P308+P313：BEI Exposition oder falls betroffen: Ärztlichen Rat einholen/ärztliche Hilfe hinzuziehen.

  P405：Unter Verschluss aufbewahren.

  P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Pomalidomide Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  In February 2013, the US FDA approved pomalidomide (also known as CC4047) for the treatment of multiple myeloma (MM) in patients with disease progression after receiving other cancer therapeutics. Pomalidomide is a 4-amino analog of thalidomide with enhanced potency and an improved toxicity profile. Pomalidomide and thalidomide exert their effects by modulation of immunity, inhibition of angiogenesis, interference with the bone/tumor microenvironment, and inhibition of the cereblon protein. Pomalidomide potently inhibited in vitro proliferation in a variety of human MM cell lines, IC₅₀～10 nM, while thalidomide showed almost no inhibition up to 100 μM. In mouse MM tumor models, 50 mg/kg daily doses of pomalidomide resulted in marked inhibition of tumor growth after 15 days of treatment and complete regression in 3–6 weeks versus thalidomide-treated controls at the same dose. Pomalidomide is prepared by condensation of 4-nitrophthalic anhydride with 3-aminopiperidine-2,6-dione followed by catalytic hydrogenation of the nitro group.

• Chemische Eigenschaften

  Yellow Solid

• Originator

  Celgene Corporation (United States)

• Verwenden

  Pomalidomide inhibits LPS-induced TNF-α release with IC50 of 13 nM

• Verwenden

  Pomalidomide is a second generation immunomodulator, TNF-α inhibitor, and thalidomide analog. An inhibitor of LPS-induced TNFαrelease.

• Verwenden

  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: Pomalidomide is 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. It has a role as an antineoplastic agent, an immunomodulator and an angiogenesis inhibitor. It is a dicarboximide, a member of isoindoles, a member of piperidones and an aromatic amine. It is functionally related to a thalidomide.

• Trademarks

  Pomalyst

• 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

• Synthese

  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.

  

• target

  TNF-α

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antidepressants: concentration increased by fluvoxamine.

• Stoffwechsel

  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.

• Lager

  Store at +4°C

• Einzelnachweise

  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) Zhu?et al.?(2013),?Molecular mechanism of action of immune-modulatory drugs thalidomide, lenalidomide and pomalidomide in multiple myeloma; Leukemia Lymphoma,?54?683
  3) KATHERINE A DONOVAN. Thalidomide promotes degradation of SALL4, a transcription factor implicated in Duane Radial Ray syndrome.[J]. eLife, 2018. DOI:10.7554/eLife.38430.
  4) Winter?et al.?(2015),?DRUG DEVELOPMENT. Phthalimide conjunction as a strategy for in vivo target protein degradation; Science,?348?1376
  5) JASMIN LOHBECK Aubry K M. Practical synthesis of a phthalimide-based Cereblon ligand to enable PROTAC development[J]. Bioorganic & Medicinal Chemistry Letters, 2016, 26 21: Pages 5260-5262. DOI:10.1016/j.bmcl.2016.09.048.

Pomalidomide Upstream-Materialien And Downstream Produkte

Pomalidomide Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(509)Suppliers

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