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Everolimus (RAD001)

Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM.

Catalog No.S1120

1 Reviews 9 Product Citations

: Tel: +1-832-582-8158[email protected]

Everolimus (RAD001) Chemical Structure
Molecular Weight: 958.22

Validation & Quality Control

Product Citations(9)

Cell, 2012, 149(3):656-70

Cancer Cell, 2012, 21(2), 155-167

Clin Cancer Res, 2013, 19(3):598-609

Clin Cancer Res, 2012, ahead of print

Neoplasia, 2010, 12(8), 637-649
Cell Death Dis, 2012, 3:e260

Aging (Albany NY), 2012, 4(2):119-32

Bioch Pharm, 2011, 82(3), 216-226

Cancer Biol Ther, 2012, 13(6):349-57

Customer Reviews(1) in vivo invitation

Quality Control & MSDS

Related Compound Libraries

Everolimus (RAD001) is available in the following compound libraries:

Cambridge Cancer Compound Library(96-well) Chemical Library (96-well) Chemotherapeutic Agent Library (96-well) Inhibitor Library (96-well) Kinase Inhibitor Library (96-well)

Product Information

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Research Area

Cat.No.	Product Name	Solubility (25°C)
S1039	Rapamycin (Sirolimus)	<1 mg/mL	20 mg/mL	4 mg/mL
S1120	Everolimus (RAD001)	<1 mg/mL	30 mg/mL	7 mg/mL
S1009	BEZ235 (NVP-BEZ235)	<1 mg/mL	1 mg/mL	<1 mg/mL
S1555	AZD8055	2 mg/mL	93 mg/mL	15 mg/mL
S1038	PI-103	<1 mg/mL	24 mg/mL	<1 mg/mL
S2811	INK 128 (MLN0128)	<1 mg/mL	62 mg/mL	2 mg/mL
S2218	PP242	<1 mg/mL	62 mg/mL	18 mg/mL
S2827	Torin 1	<1 mg/mL	2 mg/mL	<1 mg/mL
S1022	Deforolimus (Ridaforolimus)	<1 mg/mL	198 mg/mL	<1 mg/mL
S1044	Temsirolimus (Torisel)	1 mg/mL	75 mg/mL	75 mg/mL
S1226	Ku-0063794	<1 mg/mL	16 mg/mL	<1 mg/mL
S1523	XL765 (SAR245409)	<1 mg/mL	15 mg/mL	<1 mg/mL
S2658	GSK2126458	<1 mg/mL	101 mg/mL	<1 mg/mL
S2624	OSI-027	<1 mg/mL	18 mg/mL	<1 mg/mL
S2743	PF-04691502	<1 mg/mL	14 mg/mL	<1 mg/mL
S2783	AZD2014	<1 mg/mL	38 mg/mL	<1 mg/mL
S2628	PF-05212384 (PKI-587)	<1 mg/mL	2 mg/mL	<1 mg/mL
S2696	GDC-0980 (RG7422)	<1 mg/mL	20 mg/mL	<1 mg/mL
S1266	WYE-354	<1 mg/mL	99 mg/mL	<1 mg/mL
S1360	GSK1059615	<1 mg/mL	2 mg/mL	<1 mg/mL
S2661	WYE-125132	<1 mg/mL	104 mg/mL	<1 mg/mL
S2668	WYE-687	<1 mg/mL	0.5 mg/mL	<1 mg/mL
S2699	CH5132799	<1 mg/mL	12 mg/mL	<1 mg/mL
S2817	Torin 2	<1 mg/mL	22 mg/mL	<1 mg/mL
S2238	Palomid 529	<1 mg/mL	81 mg/mL	<1 mg/mL
S2622	PP-121	<1 mg/mL	64 mg/mL	2 mg/mL
S2749	NVP-BGT226	<1 mg/mL	30 mg/mL	<1 mg/mL
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S8040	GDC-0349	<1 mg/mL	91 mg/mL	6 mg/mL

Combination Therapy

Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Product Description

Biological Activity Protocol Chemical Information Customer Reviews Product Citations Tech Support & FAQs

Biological Activity

Description	Everolimus (RAD001) is an mTOR inhibitor of FKBP12 with IC50 of 1.6-2.4 nM.
Targets	mTOR (FKBP12)
IC50	1.6-2.4 nM ^[1]
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. ^[1] Everolimus also shows antiangiogenic/vascular effects in VEGF-induced HUVEC proliferationwith IC50 of 0.12 nM and bFGF-induced HUVEC proliferation with IC50 of 0.8 nM, respectively. ^[2] 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 %. ^[3]
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. ^[2] 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. ^[3]
Clinical Trials	Everolimus is currently in Phase I clinical trials in patients with Unspecified Adult Solid Tumor.
Features

Protocol(Only for Reference)

Kinase Assay: ^[1]

FKBP12 binding assay & Mixed lymphocyte reaction (MLR)	FKBP12 binding assay: Binding to the FK 506 binding protein (FKBP12) is indirectly assessed by means of an ELISA-type competition assay. FK 506 is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to FK 506 (rIC50 = IC50 Everolimus/IC50 FK 506). Mixed lymphocyte reaction (MLR): The immunosuppressive activities of RAP and its derivatives are assessed in a two-way MLR, using spleen cells of BALB/c and CBA mice. RAP is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to RAP (rIC50 = IC50 Everolimus/IC50 RAP).

FKBP12 binding assay & Mixed lymphocyte reaction (MLR)

FKBP12 binding assay: Binding to the FK 506 binding protein (FKBP12) is indirectly assessed by means of an ELISA-type competition assay. FK 506 is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to FK 506 (rIC50 = IC50 Everolimus/IC50 FK 506). Mixed lymphocyte reaction (MLR): The immunosuppressive activities of RAP and its derivatives are assessed in a two-way MLR, using spleen cells of BALB/c and CBA mice. RAP is included in each individual experiment as a standard, and the inhibitory activity is expressed as relative IC50 compared to RAP (rIC50 = IC50 Everolimus/IC50 RAP).

Cell Assay: ^[3]

Cell lines	BT474 cell line and the primary breast cancer cells
Concentrations	0.001-10 μM
Incubation Time	24 hours
Method	The 3-(4-5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction assay (MTT assay) is used to compare the effects of Everolimus or trastuzumab on total breast cancer cells and breast CSCs. The total cells and the stem cells from the BT474 cell line and the primary breast cancer cells are respectively seeded into 96-well plates with different concentrations of the drugs, with five wells for each concentration, and the cells are cultured at 37 °C with 5 % CO₂ in an incubator for 24 hours. The concentrations of Everolimus are 1 nM, 10 nM, 100 nM, 1 μM and 10 μM, and the concentrations of trastuzumab are 0.5 μg/mL, 1 μg/mL, 10 μg/mL, 50 μg/mL, and 100 μg/mL. The combinatorial inhibitory effect of Everolimus and Trastuzumab on the in vitro growth of breast CSCs is examined by MTT assay as well using 10 μg/mL trastuzumab in combination of increasing concentrations of everolimus (1 nM, 10 nM, 100 nM and 1 μM). After drug treatment for 24 hours, 20 μL MTT [5 mg/mL in phosphate buffered saline (PBS)] is added to each well, and the cells are incubated at 37 °C with 5 % CO₂ and saturated humidity for 4 hours. Following the subsequent removal of the supernatant, 150 μL dimethyl sulfoxide (DMSO) is added to each well, and the cells are vortexed for 10 minutes. The light absorbance (OD value) is measured for each well using an ELISA reader. Each experiment is repeated in triplicate, and dose–response curves are plotted. The probit software of the statistical software package SPSS 17.0 for Windows is used to calculate the inhibitory concentration (IC50) of Everolimus.

Animal Study: ^[3]

Animal Models	Cultured BT474 stem cells are injected beneath the left breast pad of BALB/c nude mice.
Formulation	Everolimus is dissolved in saline.
Dosages	≤2 mg/kg
Administration	Administered via p.o.

References

Chemical Information

Download Everolimus (RAD001) SDF

Molecular Weight (MW)	958.22
Formula	C₅₃H₈₃NO₁₄
CAS No.	159351-69-6
Synonyms	Certican, Zortress, Afinitor

Solubility (25°C) DMSO 30 mg/mL Water <1 mg/mL Ethanol 7 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	23,27-Epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine, rapamycin deriv

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Research Area

Customer Reviews (1)

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Rating

Source

Biochem Pharmacol , 2011, 82, 216-226. Everolimus (RAD001) purchased from Selleck

Method

Western blot

Cell Lines

H1299 cells

Concentrations

5 μM

Incubation Time

48 h

Results

RAD001 and other mTOR inhibitors decreased the levels of survivin protein, as assessed by Western blot analysis, without affecting the levels of other IAP members. In addition, combined treatment with sorafenib and mTOR inhibitor Rapamycin and RAD001 decreased survivin expression to a greater extent than treatment with either alone.

Product Citations (9)

NVP-BEZ235 alone and in combination in mantle cell lymphoma: an effective therapeutic strategy. [Ying H, et al. Cell 2012;149(3):656-70]
PubMed: 22541435
An animal model of MYC-driven medulloblastoma. [Pei Y, Moore CE, et al. Cancer Cell 2012;21(2), 155-167]
PubMed: 22340590
The Activation of MAPK in Melanoma Cells Resistant to BRAF Inhibition Promotes PD-L1 Expression That Is Reversible by MEK and PI3K Inhibition. [Jiang X, et al. Clin Cancer Res 2013;19(3):598-609]
PubMed: 23095323

Prognostic significance of AKT/mTOR and MAPK pathways and antitumor effect of mTOR inhibitor in NF1-related and sporadic malignant peripheral nerve sheath tumors. [Endo M, et al. Clin Cancer Res 2012;ahead of print]
PubMed: 23209032
Pharmacodynamic characterization of the efficacy signals due to selective BRAF inhibition with PLX4032 in malignant melanoma. [Tap WD, et al. Neoplasia 2010;12(8), 637-649]
PubMed: 20689758
Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells [Ajabnoor GM, et al. Cell Death Dis 2012;3:e260]
PubMed: 22278287
Automated image analysis of nuclear shape: What can we learn from a prematurely aged cell? [Driscoll MK, et al. Aging (Albany NY) 2012;4(2):119-32]
PubMed: 22354768
Sorafenib induces apoptotic cell death in human non-small cell lung cancer cells by down-regulating mammalian target of rapamycin (mTOR)-dependent survivin expression. [Kim YS, et al. Bioch Pharm 2011;82(3), 216-226]
PubMed: 21601561
Bortezomib induces apoptosis and growth suppression in human medulloblastoma cells, associated with inhibition of AKT and NF-ĸB signaling, and synergizes with an ERK inhibitor. [Yang F, et al. Cancer Biol Ther 2012;13(6):349-57]
PubMed: 22313636

Tech Support & FAQs

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Everolimus (RAD001) + Letrozole	Combination of Everolimus and Letrozole produces a synergistic effect on inhibition of proliferation and induction of apoptotic cell death in MCF7/Aro and T47D/Aro cells. ^[4]
Everolimus (RAD001) + Clafen	In a NCI-N87 human gastric cancer SCID mouse xenograft model, combination of Everolimus and Cyclophosphamide results in a more significant long-term tumor growth control compared to monotherapy and a sharp increase in central tumor necrosis. ^[5]

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Everolimus (RAD001)