Drug

D0921 | everolimus

Molecular Formula C53H83NO14
Molecular Weight 958.2
Structure
State solid
Clearance Following a 3 mg radiolabeled dose of everolimus, 80% of the radioactivity was recovered from the feces, while 5% was excreted in the urine.
Volume of distribution The blood-to-plasma ratio of everolimus is 17% to 73%.
Route of elimination After a single dose of radiolabeled everolimus was given to transplant patients receiving cyclosporine, the majority (80%) of radioactivity was recovered from the feces and only a minor amount (5%) was excreted in urine.
Protein binding ~ 74% in both healthy patients and those with moderate hepatic impairment.
Half life ~30 hours.
Absorption In patients with advanced solid tumors, peak everolimus concentrations are reached 1 to 2 hours after administration of oral doses ranging from 5 mg to 70 mg. Following single doses, Cmax is dose-proportional between 5 mg and 10 mg. At doses of 20 mg and higher, the increase in Cmax is less than dose-proportional, however AUC shows dose-proportionality over the 5 mg to 70 mg dose range. Steady-state was achieved within 2 weeks following once-daily dosing. Dose Proportionality in Patients with SEGA (subependymal giant-cell astrocytomas) and TSC (tuberous sclerosis complex): In patients with SEGA and TSC, everolimus Cmin was approximately dose-proportional within the dose range from 1.35 mg/m2 to 14.4 mg/m2.
Trade names Afinitor, Zortress
Description immunosuppressant; mTOR inhibitor

L

L04AA18 Everolimus


[L04AA] Selective immunosuppressants


[L04A] IMMUNOSUPPRESSANTS


[L04] IMMUNOSUPPRESSANTS


[L] Antineoplastic and immunomodulating agents


L01XE10 Everolimus


[L01XE] Protein kinase inhibitors


[L01X] OTHER ANTINEOPLASTIC AGENTS


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents


Toxicity Dose Time Species Model Method Action Positive criterion Reference
MEMBRANE POTENTIAL 19.86±2.83 human qHTS-HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 27.48 human HepG2 MMP assay decrease IC50 163
MEMBRANE POTENTIAL 13.01±7.49 rat hepatocytes MMP assay decrease IC50 163
SIGNALING 266

Target Dose Time Species Model Method Action Positive criterion Reference
Serine/threonine-protein kinase mTOR 266

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 94 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H372 (97.87%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H412 (43.62%): Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


P260, P264, P270, P273, P314, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


H402: Harmful to aquatic life [Hazardous to the aquatic environment, acute hazard]


H412: Harmful to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


P260, P264, P270, P273, P314, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)


  • (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.0(sup 4,9))hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.04,9)hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,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-16,24,26,28-tetraene-2,3,10,14,20-pentone
    (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone (3S,6R,7E,9R,10R,12R,14S,15E,17E,19E,21S,23S,26R,27R,34aS)-9,27-dihydroxy-3-{(2R)-1-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl]propan-2-yl}-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-hexadecahydro-3H-23,27-epoxypyrido[2,1-c][1,4]oxazacyclohentriacontine-1,5,11,28,29(4H,6H,31H)-pentone 159351-69-6
    351E696 40-O-(2-hydroxyethyl)-rapamycin 42-O-(2-Hydroxyethyl)rapamycin
    9HW64Q8G6G AKOS015850977 AS-16971
    AT-22180 Afinitor Afinitor Disperz
    BDBM50088378 BRD-K13514097-001-01-2 BRD-K13514097-001-05-3
    C53H83NO14 CAS-159351-69-6 CHEBI:68478
    CHEMBL1908360 CS-0064 Certican
    DB01590 DSSTox_CID_20599 DSSTox_GSID_40599
    DSSTox_RID_79508 DTXSID0040599 EX-A2057
    Everolimus Everolimus Everolimus (INN)
    Everolimus (RAD001) Everolimus - RAD001 Everolimus [USAN:INN:BAN]
    Everolimus [USAN] Everolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material; Everolimus solution, 1.0 mg/ml in acetonitrile
    Everolimus(RAD001) Everolimus, analytical standard GTPL5889
    HKVAMNSJSFKALM-GKUWKFKPSA-N HSDB 8255 HY-10218
    LS-143292 NCGC00167512-01 NSC733504
    NVP-RAD-001 NVP-RAD001 PubChem20048
    Q-101413 Q421052 RAD
    RAD 001 RAD 666 RAD-001
    RAD-001C RAD-666 RAD001
    RAD001 Rapamycin, 42-O-(2-hydroxyethyl)- SCHEMBL4378
    SDZ-RAD SDZ-RAD SDZRAD
    Tox21_112510 UNII-9HW64Q8G6G V2036
    Votubia XIENCE V ZINC169677008
    Zortress dihydroxy-[(1R)-2-[(1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxy-cyclohexyl]-1-methyl-ethyl]-dimethoxy-hexamethyl-[?]pentone everolimusum

    DrugBank Name everolimus
    DrugBank DB01590
    CAS Number 159351-69-6
    PubChem Compound 6442177
    KEGG Drug D02714
    ChEBI 68478
    PharmGKB PA164746311