Everolimus

Everolimus (RAD001) is a Rapamycin derivative and a potent, selective and orally active mTOR1 inhibitor. Everolimus binds to FKBP-12 to generate an immunosuppressive complex. Everolimus inhibits tumor cells proliferation and induces cell apoptosis and autophagy. Everolimus has potent immunosuppressive and anticancer activities

Product information

CAS Number: 159351-69-6

Molecular Weight: 958.22

Formula: C53H83NO14

Synonym:

RAD-001

RAD001

RAD 001

SDZ-RAD

Afinitor

Zortress

Certican

Xience V

Chemical Name: (1R, 9S, 12S, 15R, 18R, 19R, 21R, 23S, 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, ]hexatriaconta-16, 24, 26, 28-tetraene-2, 3, 10, 14, 20-pentone

Smiles: CC1=CC=CC=C[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)C(C)=C[C@@H](C)C(=O)C[C@H](OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@H](C[C@@H]1OC)CC[C@H]2C)[C@H](C)C[C@H]1C[C@@H](OC)[C@@H](CC1)OCCO |c:1,t:3,5,20|

InChiKey: HKVAMNSJSFKALM-ADNAJIBWSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 100 mg/mL(104.36 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

Everolimus exhibits the immunosuppressive activity which is comparable to that of rapamycin. Everolimus competes with immobilized FK 506 for binding to biotinylated FKBP12 and shows the inhibitory effect on a two-way MLR performed with spleen cells from BALB/c and CBA mice with IC50 of 0.12-1.8 nM. Everolimus also shows antiangiogenic/vascular effects in VEGF-induced HUVEC proliferation with IC50 of 0.12 nM and bFGF-induced HUVEC proliferation with IC50 of 0.8 nM, respectively. A recent study shows that Everolimus shows a dose-dependent inhibitory effects on both the total cells and the stem cells from the BT474 cell line and the primary breast cancer cells with IC50 of 156 nM in total cells of primary breast cancer cells and 71 nM in total cells of BT474 cells. In addition, combination treatment with Everolimus and trastuzumab produces the significantly increased inhibition on the growth of cancer stem cells with the inhibition rate increased by more than 50 %.

In Vivo:

Everolimus (0.1 to 10 mg/kg) dose-dependently inhibits growth of the primary (ear) and lymph node metastases of B16/BL6 melanoma, with decreased total number of vessels and reduced mature vessels. In a xenograft animal model of BT474 stem cells, Everolimus shows significant reductions in mean tumor sizes (590.6 mm3), compared to the control group with a tumor size of 698 mm3. Furthermore, combination treatment with Everolimus and trastuzumab significantly decreases the xenograft tumor size (410.8 mm3) more than Everolimus treatment alone.

References:

1. Zhu Y, et al. Tumour Biol. 2012 Apr 11. Doi: 10.1007/s13277-012-0383-6.
2. Lane HA, et al. Clin Cancer Res, 2009, 15(5), 1612-1622.
3. Sedrani R, et al. Transplant Proc, 1998, 30(5), 2192-2194.

Products are for research use only. Not for human use.