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Everolimus Produkt Beschreibung

Everolimus Struktur
159351-69-6
CAS-Nr.
159351-69-6
Englisch Name:
Everolimus
Synonyma:
SDZRAD;Certica;RAD-001;Zortress;Afinitor;Certican;Everolimus;CERTICAN(R);EveroliMus API;Everolimus powder
CBNumber:
CB9502411
Summenformel:
C53H83NO14
Molgewicht:
958.22
MOL-Datei:
159351-69-6.mol

Everolimus Eigenschaften

Schmelzpunkt:
NA
Siedepunkt:
998.7±75.0 °C(Predicted)
Dichte
1.18±0.1 g/cm3(Predicted)
Flammpunkt:
2℃
storage temp. 
-20°C
pka
10.40±0.70(Predicted)
Wasserlöslichkeit
Soluble in dimethysulfoxide,ethanol and chloroform. Slightly soluble in water.
Stabilität:
Hygroscopic
InChIKey
HKVAMNSJSFKALM-GKUWKFKPSA-N
Sicherheit
  • Risiko- und Sicherheitserklärung
  • Gefahreninformationscode (GHS)
Kennzeichnung gefährlicher T,Xn,F
R-Sätze: 48/25-36-20/21/22-11
S-Sätze: 45-36/37-26-16
RIDADR  UN 1648 3 / PGII
WGK Germany  2
10
HS Code  29349990
Giftige Stoffe Daten 159351-69-6(Hazardous Substances Data)
Bildanzeige (GHS)
Alarmwort Achtung
Gefahrenhinweise
Code Gefahrenhinweise Gefahrenklasse Abteilung Alarmwort Symbol P-Code
H225 Flüssigkeit und Dampf leicht entzündbar. Entzündbare Flüssigkeiten Kategorie 2 Achtung P210,P233, P240, P241, P242, P243,P280, P303+ P361+P353, P370+P378,P403+P235, P501
H319 Verursacht schwere Augenreizung. Schwere Augenreizung Kategorie 2 Warnung P264, P280, P305+P351+P338,P337+P313P
H372 Schädigt bei Hautkontakt und Verschlucken die Organe bei längerer oder wiederholter Exposition. Spezifische Zielorgan-Toxizität (wiederholte Exposition) Kategorie 1 Achtung P260, P264, P270, P314, P501
Sicherheit
P210 Von Hitze, heißen Oberflächen, Funken, offenen Flammen und anderen Zündquellenarten fernhalten. Nicht rauchen.
P260 Dampf/Aerosol/Nebel nicht einatmen.
P264 Nach Gebrauch gründlich waschen.
P264 Nach Gebrauch gründlich waschen.
P270 Bei Gebrauch nicht essen, trinken oder rauchen.
P314 Bei Unwohlsein ärztlichen Rat einholen / ärztliche Hilfe hinzuziehen.
P305+P351+P338 BEI KONTAKT MIT DEN AUGEN: Einige Minuten lang behutsam mit Wasser spülen. Eventuell vorhandene Kontaktlinsen nach Möglichkeit entfernen. Weiter spülen.

Everolimus Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:

R48/25:Giftig: Gefahr ernster Gesundheitsschäden bei längerer Exposition durch Verschlucken.

S-Sätze Betriebsanweisung:

S45:Bei Unfall oder Unwohlsein sofort Arzt zuziehen (wenn möglich, dieses Etikett vorzeigen).

Beschreibung

Everolimus, an oral immunosuppressant for the treatment of kidney and heart transplant rejection, is the 40-O-(2-hydroxyethyl) derivative of rapamycin. It has immunosuppressive properties similar to those of rapamycin, but with improved pharmacokinetic profile. In addition, the 40-O-(2-hydroxyethyl) group alters the physico-chemical properties of the macrolide to allow galenic formulation. Everolimus is prepared in a two-step semisynthesis starting from rapamycin, by alkylation of the 40-hydroxyl group with t-butyldimethylsilyloxyethyl triflate and subsequent cleavage of the silyl protecting group. Everolimus, like rapamycin, is a proliferation signal inhibitor that exerts its immunosuppressive effect by inhibiting the activation of p70 S6 kinase, thereby blocking growth factor-driven proliferation of T cells, B cells and vascular smooth muscle cells, and arresting cell cycle at the G1 phase. Inhibition of p70 S6 kinase activation by everolimus and rapamycin is mediated by their binding to FKBP12 (FK506 binding-protein 12). Everolimus inhibits FK506 binding to FKBP12 with an IC50 of 1.8–2.6 nM, and it is about 3- to 5-fold less potent than rapamycin (IC50=0.4–0.9 nM). The in vitro immunosuppressive activity of everolimus is also slightly less than that of rapamycin as demonstrated in a mixed lymphocyte reaction (MLR) assay (IC50=0.2–1.6 nM versus 0.07–0.5 nM, respectively) and in antigen-specific human helper T-cell clones (IC50=0.05–0.17nM versus 0.014–0.37nM, respectively). However, the in vivo immunosuppressive activity of oral everolimus 1–5 mg/ kg/day is similar to that of rapamycin at equivalent doses in rat models of renal or cardiac transplantation, localized graft-versus-host disease, and autoimmune glomerulonephritis. The recommended dosage of everolimus is 0.75 mg twice daily, and it is used in combination with cyclosporine microemulsion and corticosteroids. Following oral dosing, the peak concentration (Cmax) of everolimus is estimated between 1.5 to 2 hours, and steady state is achieved within 4 days. The terminal elimination half-life is 21 to 35 hours. By comparison, rapamycin has a longer elimination half-life (60 hours) and longer time to reach steady state (7 to 14 days). Consequently, rapamycin treatment requires a large loading dose, followed by once daily maintenance dose, whereas everolimus is administered twice daily but without the need of a loading dose. Everolimus is extensively metabolized, primarily by CYP3A4. Approximately 80% of the dose is excreted in the feces and about 5% in the urine. In clinical trials with adult cardiac transplant recipients, oral everolimus 0.75 or 1.5 mg twice daily significantly reduced the incidence of efficacy failure as well as cardiac allograft vasculopathy (CAV) up to 2 years after transplantation as compared with azathioprene 1–3 mg/kg/day. However, graft and patient survival rates at 1 year were similar in patients receiving everolimus and azathioprene. In trials involving renal transplant recipients, the combined incidence of biopsy-confirmed acute rejection, graft loss, death, or loss to follow-up was similar in patients receiving everolimus 1.5 or 3 mg/day or mycophenolate mofetil 2 g/day up to 3 years after transplantation. Everolimus was well tolerated in transplant patients. The incidence of viral infection including cytomegalovirus (CMV) was reduced in comparison to azathioprene and mycophenolate mofetil, but bacterial infections were more frequent. Main adverse events associated with everolimus were thrombocytopenia, leucopenia, and elevated serum lipids and creatinine.

Beschreibung

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that, as part of two distinct complexes (mTORC1 and mTORC2), plays pivotal roles in intracellular signaling. Everolimus is a hydroxyethyl ether rapamycin (Item No. 13346) derivative that inhibits mTOR signaling through both mTORC1 and mTORC2 when added to cells at 20 nM. It is orally available and shows improved pharmacokinetics and pharmacodynamics over rapamycin. Through its inhibition of mTOR, everolimus inhibits cell proliferation, metabolism, and angiogenesis in certain types of cancer. It also acts as an immunosuppressive agent in the context of organ transplantation.

Chemische Eigenschaften

Off White Solid

Originator

Novartis (Switzerland)

Verwenden

Macrolide immunosuppressant; derivative of Rapamycin. Inhibits cytokine-mediated lymphocyte proliferation

Verwenden

Everolimus Macrolide immunosuppressant; Everolimus is a derivative of Rapamycin. Everolimus inhibits cytokine-mediated lymphocyte proliferation.

Verwenden

Everolimus is a semi-synthetic macrocyclic lactone prepared from rapamycin by selective alkylation of the 42-hydroxy group with a silyl-protected hydroxyethyl triflate moiety, followed by addition of an ethylhydroxy moiety to provide greater stability and bioavailability. Like all tacrolimus analogues, everolimus binds to receptor protein, FKBP12. The complex then binds to mTOR preventing it from interacting with target proteins. Everolimus is extensively cited in the literature with over 2,000 citations.

Verwenden

Everolimus (IX) (SDZ-RAD), was developed by Novartis as an immunosuppressant to be used in conjunction with cyclosporin in transplantation allograft rejection and was recently approved in the US in 2003. Another natural product that had been approved for use in transplantation is rapamycin (sirolimus) as an inejectable agent. In an attempt to develop an orally bioavailable immunosuppressant agent, many companies attempted modification of rapamycin itself.

Definition

ChEBI: A macrocyclic lactone that is rapamycin in which the hydroxy group attached to the cyclohexyl moiety has been converted to the corresponding 2-hydroxyethyl ether. It is an immunosuppressant and antineoplastic agent.

Trademarks

Certican

Allgemeine Beschreibung

Everolimus, sold under trade names including Zortress?, Certican, and Afinitor?, is an immunosuppressant drug used to prevent rejection of organ transplants and to treat renal cell cancer and other tumors. This Certified Spiking Solution? is suitable as starting material for calibrators, controls, or linearity standards for therapeutic drug monitoring or clinical and diagnostic testing of everolimus in patient whole blood samples by LC-MS/MS.

Biochem/physiol Actions

Everolimus, the 40-O-(2-hydroxyethyl) derivative of rapamycin (sirolimus), is a potent and selective inhibitor of mechanistic target of rapamycin (mTOR). Everolimus is selective for the mTORC1 protein complex. Everolimus exhibit potent immunosuppressive and anticancer activities.

Chemical Synthesis

Everolimus (IX) was discovered by Sandoz (Novartis) scientists by modifying rapamycin drug in the 40-hydroxyl position. Thus, treatment of rapamycin (84) with t-butyldimethylsilyloxy ethyl triflate in the presence of 2,6-lutidine at 60°C for 3.5 hrs gave ether 85. Deprotection of the silyl group was done by treating silyloxy ether 85 in methanol with 2N HCl to give the product IX (everolimus), which was purified by chromatography. No yields were given for the reactions.

Everolimus Upstream-Materialien And Downstream Produkte

Upstream-Materialien

Downstream Produkte


Everolimus Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

Global( 384)Lieferanten
Firmenname Telefon Fax E-Mail Land Produktkatalog Edge Rate
Wuhan Dujiang Industrial Co., Ltd.
+8618120567669 +86-027-87110040
WhatsApp:+86 18120567669 wei@dujiangsy.com CHINA 403 58
TianYuan Pharmaceutical CO.,LTD
+86-755-23284190 13684996853
+86-755-23284190 sales@tianpharm.com CHINA 305 58
Casorganics US Corp
+17326109938
sales@casorganics.com CHINA 175 58
ATK CHEMICAL COMPANY LIMITED
+86 21 5161 9050/ 5187 7795
+86 21 5161 9052/ 5187 7796 ivan@atkchemical.com CHINA 26782 60
Finetech Industry Limited
86 27 87465837
86 27 87772287 info@finetechnology-ind.com CHINA 9373 58
AFINE CHEMICALS LIMITED
008657185134551
008657185134895 info@afinechem.com CHINA 15559 58
Capot Chemical Co.,Ltd.
+86(0)13336195806 +86-571-85586718
+86-571-85864795 sales@capotchem.com China 20012 60
Beijing Cooperate Pharmaceutical Co.,Ltd
010-60279497
010-60279497 sales01@cooperate-pharm.com CHINA 1817 55
Henan Tianfu Chemical Co.,Ltd.
0371-55170693
0371-55170693 info@tianfuchem.com China 22607 55
Hangzhou FandaChem Co.,Ltd.
008615858145714
+86-571-56059825 fandachem@gmail.com CHINA 9115 55

159351-69-6()Verwandte Suche:


  • Everolimus(mixture of isomers)
  • Everolimus powder
  • CERTICAN; ZORTRESS; AFINITOR
  • Rapamycin, 42-O-(2-hydroxyethyl)-
  • Everolimus
  • Certican
  • CERTICAN(R)
  • EveroliMus(RAD-001)
  • (1R,9S,12S,15R,16Z,18R,19R,21R,23S,24Z,26Z,28Z,30S,32S,35R)-1,18-dihydroxy-12-[(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-Methoxycyclohexyl]propan-2-yl]-19,30-diMethoxy-15,17,21,23,29,35-hexaMethyl-11,36-dioxa-4-azatricyclo[30.3.1.0^{4,9}]hexatriaconta-16,2
  • Afinitor
  • Zortress
  • EveroliMus API
  • Everolimus 159351-69-6
  • 40-O-(2-Hydroxyethyl) Rapamycin
  • EVEROLIMUS(2.0% BHT)
  • EVEROLIMUS(WITHOUT BHT)
  • 23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, rapamycin deriv
  • Everolimus solution
  • Everolimus, >=98%
  • 42-O-(2-Hydroxyethyl)-rapamycin
  • Certica
  • RAD-001
  • SDZRAD
  • Everolimus (~90% pure)
  • Everolimus fandachem
  • Everolimus USP/EP/BP
  • Everolimus AFINITOR
  • Everolimus (RAD-001, SDZ-RAD)
  • 159351-69-6
  • 159351-69-7
  • C53H83NO14
  • 95822
  • Akt
  • mTOR
  • PI3K
  • Anti-cancer&immunity
  • PI3K/Akt/mTOR
  • Inhibitor
  • Antineoplastic protein kinase inhibitors
  • mTOR inhibitor
  • Certican, Zortress, Afinitor
  • Everolimus
  • All Inhibitors
  • Inhibitors
  • Intermediates & Fine Chemicals
  • Pharmaceuticals
  • API
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