Ribociclib

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

• Sicherheit

  P280：Schutzhandschuhe/Schutzkleidung/Augenschutz tragen.

  P305+P351+P338：BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

Ribociclib Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  LEE011 is a cyclin-dependent kinase (CDK) inhibitor that targets cyclin D1/CDK4 and cyclin D3/CDK6 at nanomolar concentrations. It inhibits retinoblastoma protein phosphorylation, which prevents CDK-mediated G₁-S phase transition, arresting the cell cycle in the G₁ phase, suppressing DNA synthesis, and inhibiting cancer cell growth. LEE011 has been shown to reduce proliferation in 12 of 17 human neuroblastoma-derived cell lines by inducing cytostasis (mean IC₅₀ = 306 nM in sensitive lines).

• Charakteristisch

  Class: serine/threonine protein kinase
  Treatment: Breast cancer
  Oral bioavailability = 66%
  Elimination half-life = 32 h
  Protein binding = 70%

• Verwenden

  LEE 011 can be used in biological study of kinome-wide RNA interference screen reveals a role for PDK1 in acquired resistance to CDK4/6 inhibition in ER-positive breast cancer.

• Mechanism of action

  Ribociclib is a dual cdk4/cdk6 inhibitor. Induces G1 phase cell cycle arrest and senescence in neuroblastoma cell lines (IC50 = 306 nM). Delays tumor growth in vivo.

• Clinical Use

  Protein kinase inhibitor:
  Treatment of breast cancer

• Clinical Use

  Ribociclib was first approved in 2017 as the second CDK4/6 (cyclin-dependent kinase) inhibitor in combination with aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2?) advanced or metastatic breast cancer. In 2018, its label was expanded to pre/perimenopausal women with HR+/HER2? advanced or metastatic breast cancer.
  

• target

  CDK4

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  The concomitant use of strong CYP3A4 inhibitors including, but not limited to, the following must be avoided: clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil and voriconazole.
  The concomitant use of strong CYP3A4 inducers may therefore lead to decreased exposure and consequently a risk for lack of efficacy. The concomitant use of strong CYP3A4 inducers should be avoided, including, but not limited to, phenytoin, rifampicin, carbamazepine and St John's wort.
  Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of drug transporters P-gp, BCRP, OATP1B1/1B3, OCT1, OCT2, MATE1 and BSEP which exhibit a narrow therapeutic index, including but not limited to digoxin, pravastatin, rosuvastatin and metformin.
  Co-administration of Kisqali with medicinal products with a known potential to prolong the QT interval such as anti-arrhythmic medicinal products (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine and sotalol), and other medicinal products that are known to prolong the QT interval (including, but not limited to, chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin, pimozide and intravenous ondansetron) should be avoided.

• Stoffwechsel

  Ribociclib is hepatically metabolised via CYP3A4 by oxidation. Ribociclib was the main circulating drug in plasma (44%). The major circulating metabolites included metabolite M13 (CCI284, N-hydroxylation), M4 (LEQ803, N-demethylation), and M1 (secondary glucuronide). Clinical activity of ribociclib was due mainly to parent drug, with negligible contribution from circulating metabolites. Unchanged drug accounted for 17.3% and 12.1% of the dose in faeces and urine, respectively. Metabolite LEQ803 represented approximately 13.9% and 3.74% of the administered dose in faeces and urine, respectively. Numerous other metabolites were detected in both faeces and urine in minor amounts (≤2.78%).
  Ribociclib and its metabolites are eliminated mainly via faeces (69.1%), with a small contribution from the renal route (22.6%).

• Lager

  Store at -20°C

• Einzelnachweise

  1) Rader?et al.?(2013),?Dual CDK4/6 inhibition induces cell-cycle arrest and senescence in neuroblastoma; Clin. Cancer Res.?19?6173 2) Kim?et al. (2013),?LEE011: an orally bioavailable, selective small-molecule inhibitor of CDK4/6 – reactivating Rb in cancer; Mol. Cancer Ther.?12?PR02 3) Tripathy?et al.?(2017),?Ribociclib(LEE011): mechanism of action and clinical impact of this selective cyclin-dependent kinase 4/6 inhibitor in various solid tumors; Clin. Cancer Res. March 28, 201

Ribociclib Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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