Letrozole

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H373：Kann die Organe schädigen bei längerer oder wiederholter Exposition.

• Sicherheit

  P202：Vor Gebrauch alle Sicherheitshinweise lesen und verstehen.

  P260：Dampf/Aerosol/Nebel nicht einatmen.

  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.

Letrozole Chemische Eigenschaften,Einsatz,Produktion Methoden

• R-Sätze Betriebsanweisung:

  R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.

• S-Sätze Betriebsanweisung:

  S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
  S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.

• Beschreibung

  Letrozole, also known as Femara, is an orally active aromatase inhibitor that works by competitively inhibiting aromatase. This inhibition prevents the conversion of androgens to estrogen (estrogen stimulates breast tissues and breast cancer reoccurrence) and gonadal steroidogenesis. It can be used for the treatment of breast cancer that is hormonally-responsive or has an unknown receptor status in postmenopausal women. Besides this, Letrozole also has some off-label use such as ovarian stimulation, pretreatment of termination of pregnancy, treatment of gynecomastia, treatment of endometriosis, and promoting spermatogenesis for male patients of nonobstructive azoospermia.

• Chemische Eigenschaften

  white to light yellow crystal

• Originator

  Novartis (Switzerland)

• Verwenden

  A nonsteroidal aromatase inhibitor structurally related to Fadrozole. Antineoplastic

• Verwenden

  Letrozole has been used:
  
  • in organoid growth assay to determine its inhibitory capacity(48)
  • to investigate steroid receptor coactivator-1 (SRC-1) mediated endogenous estrogen regulation of hippocampal PSD-95(49)
  • to determine its effects on tumor-induced hyperalgesia(50)
  • for hormonal manipulation in rats(51)
  • to study its effects on lipocalin-2 (Lcn2)(52)
  • to determine its effects on mechanical hyperalgesia and aromatase expression(53)
  
  

• Definition

  ChEBI: Letrozole is a member of triazoles and a nitrile. It has a role as an antineoplastic agent and an EC 1.14.14.14 (aromatase) inhibitor.

• Manufacturing Process

  From 4-bromomethylbenzonitrile and 1H-[1,2,4]triazole was obtained 4- [1,2,4]triazol-1-ylmethylbenzonitrile. Treatment of that with strong base (tertBuOK) results in formation of the anion by removal of the relatively acidic benzyl proton. This anion was condensed with p-fluorobenzinitrile to give benzhydryl tetrazole (Letrozole)

• Trademarks

  Femara (Novar tis).

• Therapeutic Function

  Antineoplastic

• Allgemeine Beschreibung

  Letrozole, 4,4'-(1H-1,2,4-triazol-1-ylmethylene)dibenzonitrile (Femara), is used for most of thesame indications as anastrozole. It reduces concentrations ofestrogens by 75% to 95%, with maximal suppressionachieved within 2 to 3 days. Letrozole is specific for aromataseinhibition, with no additional effects on adrenal corticoidbiosynthesis. CYPs 3A4 and 2A6 are involved in themetabolism of letrozole to the major carbinol metabolite,which is inactive. The loss of the triazole ring, which is involvedin coordination of the heme iron, would explain theloss of activity. Letrozole strongly inhibits CYP2A6 invitro, with moderate inhibition of CYP2C19. The effect ofthis in vitro inhibition on the pharmacokinetics of coadministereddrugs is unknown. Tamoxifen reduces the levels ofletrozole significantly if they are used together, so combinationtreatment with these agents is not recommended.

• Biologische Aktivität

  Letrozole is a potent, cell-permeable inhibitor of aromatase (IC50 = 2 nM). It inhibits proliferation of estrogen receptor-positive (ER+) MCF-7 cells when used alone at concentrations ranging from 0.1 to 100 nM and when used at a concentration of 10 nM in combination with testosterone or 4-androstene-3,17-dione. It also reduces matrix metalloproteinase-2 (MMP-2) and MMP-9 levels in MCF-7 cells when used at a concentration of 10 nM. Letrozole (10 μg per day) reduces tumor growth in an MCF-7Ca ovariectomized-mouse xenograft model. Formulations containing letrozole have been used in the treatment of postmenopausal breast cancer.

• Biochem/physiol Actions

  Letrozole is a third generation nonsteroidal aromatase inhibitor. It is a competitive inhibitor of the aromatase enzyme system and thus inhibits the conversion of androgens to estrogens. Letrozole inhibits the aromatase enzyme by competitively binding to the heme of the cytochrome P450 subunit of the enzyme, resulting in a reduction of estrogen biosynthesis in all tissues.

• Mechanism of action

  Inhibition of arom atase by letrazole is competitive and highly specific , with no effect on enzymes that are responsible for the production of glucocorticosteroids and mineralocorticosteroids. This agent is significantly more effective than tamoxifen in treating horm one-dependent cancer.

• Clinical Use

  Femara was launched in France and the UK for second-line treatment of advanced breast cancer. Letrazole can be synthesized in two steps from 4- bromomethyl-benzonitrile with 1,2,4-triazole and is a third generation aromatase inhibitor. It is a highly specific inhibitor of P450_arom which prevents the conversion of androstenedione to estrone. The reduction of plasma estrogen was immediate and long lasting. This is accomplished with no inhibition of other steroid biosynthesis making it the most selective aromatase inhibitor tested. Letrazole has remarkable antitumor activity, is well tolerated and has no toxic side effects. It is 10,000 times more potent than aminoglutethimide, in vivo, the first well established aromatase inhibitor.

• Lager

  Store at +4°C

• Einzelnachweise

  https://www.drugbank.ca/drugs/DB01006
  https://en.wikipedia.org/wiki/Letrozole

Letrozole Upstream-Materialien And Downstream Produkte

Letrozole Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global(715)Suppliers

112809-51-5, Letrozole Verwandte Suche: