Ponatinib

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Achtung

• Gefahrenhinweise

  H372：Schädigt bei Hautkontakt und Verschlucken die Organe bei längerer oder wiederholter Exposition.

• Sicherheit

  P260：Dampf/Aerosol/Nebel nicht einatmen.

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P301+P310：BEI VERSCHLUCKEN: Sofort GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

Ponatinib Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Ponatinib (943319-70-8) is a highly potent pan-Bcr-Abl and multikinase inhibitor, suppressing the activity of native Bcr-Abl (IC50=0.37 nM) as well as the mutants T315I (IC50=2 nM), Q252H (IC50=0.44 nM), Y253F (IC50=0.3 nM), M351T (IC50=0.3 nM) and H396P (IC50=0.34 nM).1??Also inhibits PDGFRα, c-Src and c-Kit (IC50=1.1, 5.4 and 12.5 nM respectively)2?as well as FGFR-mediated signaling (IC50<40 nM)3. Protects against influenza A virus-induced death by suppressing cytokine storm in mouse models..4

• Chemische Eigenschaften

  Pale Yellow Solid

• Verwenden

  AP24534 is a novel potent, orally available small molecule multitargeted kinase inhibitor with IC50 of 0.37, 2, 1.5, 2.2, 1.1, 1and 0.24 nM for native pan-BCR-ABL, mutated form, VEGFR2, FGFR1, PDGFRα, mutant FLT3 phosphorylation and LYN.

• Verwenden

  Ponatinib (AP24534) is a novel, potent multi-target inhibitor of Abl, PDGFRα, VEGFR2, FGFR1 and Src with IC50 of 0.37 nM, 1.1 nM, 1.5 nM, 2.2 nM and 5.4 nM, respectively

• Verwenden

  Ponatinib (AP24534) is a novel potent, orally available small molecule multitargeted kinase inhibitor. Ponatinib inhibits both native and mutant BCR-ABL. Ponatinib is used in the treatment of chronic myeloid leukemia (CML) with BCR-ABL kinase inhibitors.

• Definition

  ChEBI: A benzamide obtained by the formal condensation of the carboxy group of 3-(imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzoic acid with the anilino group of 4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)aniline.

• Trademarks

  Iclusig^TM

• Allgemeine Beschreibung

  Ponatinib, a third-generation BCR-ABL tyrosine kinase inhibitor (TKI), was first approved in December 2012 as a third-line treatment for CML patients. However, three months later, its approval was suspended, primarily due to safety concerns arising from the increased incidence of serious vascular occlusive events. Because there was no alternative treatment option at the time for CML patients with the T315I mutation, the suspension was lifted after a couple of months, and ponatinib was reintroduced for adult patients with T315I-postive CML (including accelerated, chronic, or blast phases) or those with T315I-positive Ph+ ALL with multiple safety measures regarding cardiovascular risk. Class: non-receptor tyrosine kinase
  Treatment: CML
  Elimination half-life = 24 h
  Protein binding = 99%

• Clinical Use

  Protein kinase inhibitor:
  
  Treatment of chronic myeloid leukaemia (CML)
  
  Treatment of Philadelphia chromosome positive acute lymphoblastic leukaemia (Ph+ ALL)

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antibacterials: concentration reduced by rifampicin - avoid.
  Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).

• Stoffwechsel

  Ponatinib is metabolised to an inactive carboxylic acid by esterases and/or amidases, and metabolised by CYP3A4 to an N-desmethyl metabolite that is 4 times less active than ponatinib.
  Ponatinib is mainly eliminated via faeces. Following a single oral dose of [14C]-labelled ponatinib, approximately 87% of the radioactive dose is recovered in the faeces and approximately 5% in the urine.

• Lager

  Store at -20°C

• Einzelnachweise

  1) O’Hare?et al.?(2009),?AP24534, a pan-BCR-ABL inhibitor for chronic myeloid leukemia, potently inhibits the T315I mutant and overcomes mutation-based resistance; Cancer Cell,?16?401 2) Gozgit?et al.?(2011),?Potent activity of ponatinib (AP24535) in models of FLT3-driven acute myeloid leukemia and other hematologic malignancies; Mol. Cancer Ther.,?10?1028 3) Gozgit?et al.?(2012),?Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models; Mol. Cancer Ther.,?11?690 4) Chen?et al.?(2019),?Ponatinib Protects Mice From Lethal Influenza Infection by Suppressing Cytokine Storm; Front. Immunol., 10 1393

Ponatinib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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