MITOTOX

Drug

D0921 | everolimus

Properties

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

Therapeutic Classification Source: DrugBank

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

Mitochondrial Toxicity Evaulation

Toxicity	Dose	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

Targets

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

GHS Hazard Tables Source: PubChem

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.)

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]