A8169-25mg | Everolimus (RAD001) [159351-69-6] Clinisciences

Background

Everolimus, also known as RAD001, is a potent and orally bio-available inhibitor of mammalian target of rapamycin (mTOR), a key component of active PI3K/Akt pathway in human cancers. It binds to intracellular receptor FKBP12 in the mTOR pathway with high affinity forming an everolimus-FKBP12 complex. The complex further binds to mTOR resulting in reducing the activity of the downstream effectors S6 ribsomal protein kinase (S6K1) and translational repressor protein eukaryotic elongation factor 4E-binding protein (4EBP). Besides its immunosuppressive activity for the prevention of organ transplant rejection, everolimus exhibits antineoplastic activity and is currently used to treat renal cell cancer and other tumors.

Reference

G Anandappa, AE Hollingdale, and TG Eisen. Everolimus – a new approach in the treatment of renal cell carcinoma. Cancer Management and Research 2010:2 61-70

Laura Elibenschutz, Delia Colombo, and Caterina Catricala. Everolimus for compassionate use in multiple basal cell carcinomas. Case Reports in Dermatological Medicine 2013

Raffaele Pezzani, Beatrice Rubin, Marco Redaelli, Claudia Radu, Susi Barollo, Maria Verena Cicala, Monica Salva, Caterina Mian, Carla Mucignat-Caretta, Paolo Simioni, Maurizio Iacobone and Franco Mantero. The antiproliferative effects of ouabain and everolimus on adrenocortical tumor cells. Endocrine journal, 2013

Product Citation

1. Jing Ma, Chao Dong, et al. "Dual Target of EGFR and mTOR Suppress Triple Negative Breast Cancer Cell Growth Via Regulation The Phosphorylation of mTOR Downstream Proteins." Breast Cancer (Dove Med Press). 2023 Jan 17;15:11-24. PMID: 36691572
2. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
3. Narin Ozturk, Dilek Ozturk Civelek, et al. "Dosing-time dependent testicular toxicity of everolimus in mice." Eur J Pharm Sci. 2021 Oct 1;165:105926. PMID: 34242751
4. Silvia-Elena Glont. "Novel insights into the molecular mechanisms of endocrine resistance in ERα positive breast cancer." journal.pone.0215340. April 10, 2019.
5. Syafruddin SE, Rodrigues P, et al. "A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma." Nat Commun. 2019 Mar 11;10(1):1152. PMID: 30858363
6. Hegab AE, Ozaki M, et al. "Calorie restriction enhances adult mouse lung stem cells function and reverses several ageing-induced changes." J Tissue Eng Regen Med. 2018 Dec 18. PMID: 30562419
7. Wang H, Tian L, et al. "The Osteogenic Niche Is a Calcium Reservoir of Bone Micrometastases and Confers Unexpected Therapeutic Vulnerability." Cancer Cell. 2018 Nov 12;34(5):823-839.e7. PMID: 30423299
8. Hegab AE, Ozaki M, et al. "High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects." Stem Cell Res. 2018 Oct 4;33:25-35. PMID: 30308415
9. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID: 30038713
10. Li J, Zhang J, et al. "Silencing lnc-ASAH2B-2 Inhibits Breast Cancer Cell Growth via the mTOR Pathway." Anticancer Res. 2018 Jun;38(6):3427-3434. PMID: 29848693
11. Ozturk N, Ozturk D, et al. "The immune system as a chronotoxicity target of the anticancer mTOR inhibitor everolimus." Chronobiol Int. 2018 Feb 5:1-14. PMID: 29400578
12. Peng T, Dou QP. "Everolimus Inhibits Growth of Gemcitabine-Resistant Pancreatic Cancer Cells via Induction of Caspase-Dependent Apoptosis and G(2) /M Arrest." J Cell Biochem. 2017 Feb 6. PMID: 28165150

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Chemical Properties

Physical Appearance	A solid
Storage	Store at -20°C
M.Wt	958.22
Cas No.	159351-69-6
Formula	C₅₃H₈₃NO₁₄
Synonyms	Everolimus, RAD001
Solubility	≥47.91 mg/mL in DMSO; insoluble in H2O; ≥122 mg/mL in EtOH
SDF	Download SDF
Canonical SMILES	OCCO[C@H]1[C@H](OC)C[C@H](C[C@H](C)[C@H](CC([C@H](C)/C=C(C)/[C@@H](O)[C@H]2OC)=O)OC([C@@H]3CCCCN3C(C([C@@]4(O)[C@H](C)CC[C@@H](C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C2=O)O4)=O)=O)=O)CC1
Shipping Condition	Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice.
General tips	We do not recommend long-term storage for the solution, please use it up soon.

Protocol

Cell experiment: [1]
Cell lines	The pancreatic tumor cell line Panc-1 and the small cell lung cancer cell line ScLc.
Preparation method	The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20°C for several months.
Reaction Conditions	IC50: 50 μg/mL (Panc-1); 5 μg/mL (ScLc), 24h
Applications	Everolimus exerted antiproliferation activity. It dose-dependently inhibited BrdU incorporation in Panc-1 and ScLc with IC50 values of 50 μg/mL and 5 μg/mL, respectively. Both are high concentrations that would not be possible in humans. Therapeutic serum levels of everolimus range between 0.005 and 0.01 μg/mL.
Animal experiment : [2]
Animal models	TgMISIIR-TAg-DR26 mice model of ovarian cancer
Dosage form	RAD001 was formulatedat 2% (w/v) in a microemulsion vehicle and was diluted in double-distilled water just before administration by gavage. Mice were treated with placebo (control) or 5 mg/kg of RAD001 twice weekly started from age of 5 weeks and continued to 20 weeks. Mice treated with placebo or RAD001 were scanned by MRM.
Applications	RAD001 suppressed tumorigenesis. Body weights of RAD001-treated mice were ~10% lower than in placebo treated mice.
Other notes	Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
References: [1] Stracke S, Ramudo L, Keller F, et al. Antiproliferative and overadditive effects of everolimus and mycophenolate mofetil in pancreas and lung cancer cells in vitro. Transplantation proceedings. Elsevier, 2006, 38(3): 766-770. [2] Mabuchi S, Altomare D A, Connolly D C, et al. RAD001 (Everolimus) delays tumor onset and progression in a transgenic mouse model of ovarian cancer. Cancer Research, 2007, 67(6): 2408-2413.