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Details

Stereochemistry ABSOLUTE
Molecular Formula C53H83NO14
Molecular Weight 958.2244
Optical Activity UNSPECIFIED
Defined Stereocenters 15 / 15
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of EVEROLIMUS

SMILES

[H][C@@]12CC[C@@H](C)[C@@](O)(O1)C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@@H](CC(=O)[C@H](C)\C=C(C)\[C@@H](O)[C@@H](OC)C(=O)[C@H](C)C[C@H](C)\C=C\C=C\C=C(C)\[C@H](C2)OC)[C@H](C)C[C@@H]4CC[C@@H](OCCO)[C@@H](C4)OC

InChI

InChIKey=HKVAMNSJSFKALM-GKUWKFKPSA-N
InChI=1S/C53H83NO14/c1-32-16-12-11-13-17-33(2)44(63-8)30-40-21-19-38(7)53(62,68-40)50(59)51(60)54-23-15-14-18-41(54)52(61)67-45(35(4)28-39-20-22-43(66-25-24-55)46(29-39)64-9)31-42(56)34(3)27-37(6)48(58)49(65-10)47(57)36(5)26-32/h11-13,16-17,27,32,34-36,38-41,43-46,48-49,55,58,62H,14-15,18-26,28-31H2,1-10H3/b13-11+,16-12+,33-17+,37-27+/t32-,34-,35-,36-,38-,39+,40+,41+,43-,44+,45+,46-,48-,49+,53-/m1/s1

HIDE SMILES / InChI

Molecular Formula C53H83NO14
Molecular Weight 958.2244
Charge 0
Count
MOL RATIO 1 MOL RATIO (average)
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 15 / 15
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Everolimus is a derivative of Rapamycin (sirolimus), it is a mTOR inhibitor that binds with high affinity to the FK506 binding protein-12 (FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. Everolimus is indicated for the treatment of postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer (advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole. Indicated for the treatment of adult patients with progressive neuroendocrine tumors of pancreatic origin (PNET) with unresectable, locally advanced or metastatic disease. Indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Indicated for the treatment of adult patients with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery. Indicated in pediatric and adult patients with tuberous sclerosis complex (TSC) for the treatment of subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but cannot be curatively resected. Everolimus is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and as Afinitor (general tumours) and Votubia (tumours as a result of TSC) in oncology. Everolimus is also available from Biocon, with the brand name Evertor, from Natco Pharma, with the brand name Temonat, from Ranbaxy Laboratories, with the brand name of Imozide, from Emcure Pharmaceuticals, with the brand name of Temcure, among over 20 different brands.

CNS Activity

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
13.5 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
AFINITOR
Primary
AFINITOR
Primary
AFINITOR

Cmax

ValueDoseCo-administeredAnalytePopulation
61.5 ng/mL
10 mg 1 times / day steady-state, oral
EVEROLIMUS blood
Homo sapiens
18.84 ng/mL
2 mg single, oral
EVEROLIMUS plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
435 ng × h/mL
10 mg 1 times / day steady-state, oral
EVEROLIMUS blood
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
45.74 h
2 mg single, oral
EVEROLIMUS plasma
Homo sapiens

Funbound

ValueDoseCo-administeredAnalytePopulation
27%
EVEROLIMUS plasma
Homo sapiens

Doses

AEs

Drug as perpetrator​

Drug as victim

Tox targets

PubMed

Sample Use Guides

In Vivo Use Guide
Advanced HR+ BC, advanced NET, advanced RCC, or renal angiomyolipoma with TSC: 10 mg once daily with or without food.
Route of Administration: Oral
In Vitro Use Guide
Everolimus effectively inhibited cell growth at concentrations under 100 nM (IC(50)) in five triple-negative breast cancers cell lines and even in the 1-nM range in three of the five cell lines.
Substance Class Chemical
Record UNII
9HW64Q8G6G
Record Status Validated (UNII)
Record Version