WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 204520
CAS#: 1009298-59-2
Description: Vistusertib, also known as AZD2014, is an orally bioavailable inhibitor of the mammalian target of rapamycin (mTOR) with potential antineoplastic activity. mTOR kinase inhibitor AZD2014 inhibits the activity of mTOR, which may result in the induction of tumor cell apoptosis and a decrease in tumor cell proliferation. mTOR, a serine/threonine kinase that is upregulated in a variety of tumors, plays an important role downstream in the PI3K/Akt/mTOR signaling pathway.
MedKoo Cat#: 204520
Name: Vistusertib (AZD-2014)
CAS#: 1009298-59-2
Chemical Formula: C25H30N6O3
Exact Mass: 462.23794
Molecular Weight: 462.54
Elemental Analysis: C, 64.92; H, 6.54; N, 18.17; O, 10.38
Synonym: AZD2014, AZD-2014, AZD 2014, Vistusertib
IUPAC/Chemical Name: 3-[2,4-Bis((3S)-3-methylmorpholin-4-yl)pyrido[5,6-e]pyrimidin-7-yl]-N-methylbenzamide
InChi Key: JUSFANSTBFGBAF-IRXDYDNUSA-N
InChi Code: InChI=1S/C25H30N6O3/c1-16-14-33-11-9-30(16)23-20-7-8-21(18-5-4-6-19(13-18)24(32)26-3)27-22(20)28-25(29-23)31-10-12-34-15-17(31)2/h4-8,13,16-17H,9-12,14-15H2,1-3H3,(H,26,32)/t16-,17-/m0/s1
SMILES Code: O=C(NC)C1=CC=CC(C2=CC=C3C(N4[C@@H](C)COCC4)=NC(N5[C@@H](C)COCC5)=NC3=N2)=C1
Appearance: Yellow solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | Vistusertib (AZD2014) is an ATP competitive mTOR inhibitor with an IC50 of 2.81 nM. |
| In vitro activity: | As shown by the results, in all the CRPC cell lines, AZD2014 effectively blocked the phosphorylation of 4EBP1 at Thr37/46 and that of AKT at Ser473 in a concentration‐dependent manner, and this inhibitory effect was especially significant when the concentration was 100 nM or more. In contrast, rapamycin also had a certain weak inhibitory effect on 4EBP1 phosphorylation at Thr37/46 in a concentration‐dependent manner but had little inhibitory effect on AKT phosphorylation at Ser473 even at a high concentration of 1000 nM (Figure 1A‐D). These results demonstrate that AZD2014 is a potent inhibitor of mTORC1 and mTORC2 in CRPC cells that blocks mTOR signalling more thoroughly than rapamycin. Reference: J Cell Mol Med. 2021 Mar; 25(5): 2436–2449. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933970/ |
| In vivo activity: | Seventy-two hours thereafter, spleens were harvested and alloreactive tg T cell proliferation assessed by flow cytometry (Figure 4A). Compared to vehicle control-treated mice, those injected with either RAPA (1 mg/kg) or AZD2014 (10 mg/kg bid) showed marked inhibition of alloreactive CD4+ T cell proliferation (Figure 4B and C). Reference: Transplantation. 2017 Dec; 101(12): 2830–2840. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5709200/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 47.67 | 103.06 | |
| DMF | 10.0 | 21.62 | |
| Ethanol | 0.5 | 1.08 |
The following data is based on the product molecular weight 462.54 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Li S, Sheng J, Liu Z, Fan Y, Zhang C, Lv T, Hu S, Jin J, Yu W, Song Y. Potent antitumour of the mTORC1/2 dual inhibitor AZD2014 in docetaxel-sensitive and docetaxel-resistant castration-resistant prostate cancer cells. J Cell Mol Med. 2021 Mar;25(5):2436-2449. doi: 10.1111/jcmm.16155. Epub 2021 Jan 28. PMID: 33507584; PMCID: PMC7933970. 2. Kim HK, Kim SY, Lee SJ, Kang M, Kim ST, Jang J, Rath O, Schueler J, Lee DW, Park WY, Kim SJ, Park SH, Lee J. BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells. Transl Oncol. 2016 Jun;9(3):197-202. doi: 10.1016/j.tranon.2016.03.008. Epub 2016 May 12. PMID: 27267837; PMCID: PMC4907899. 3. Jones AT, Yang J, Narov K, Henske EP, Sampson JR, Shen MH. Allosteric and ATP-Competitive Inhibitors of mTOR Effectively Suppress Tumor Progression-Associated Epithelial-Mesenchymal Transition in the Kidneys of Tsc2+/- Mice. Neoplasia. 2019 Aug;21(8):731-739. doi: 10.1016/j.neo.2019.05.003. Epub 2019 Jun 14. PMID: 31207499; PMCID: PMC6580094. 4. Fantus D, Dai H, Ono Y, Watson A, Yokota S, Mohib K, Yoshida O, Ross MA, Watkins SC, Ramaswami B, Valusjkikh A, Rothstein DM, Thomson AW. Influence of the Novel ATP-Competitive Dual mTORC1/2 Inhibitor AZD2014 on Immune Cell Populations and Heart Allograft Rejection. Transplantation. 2017 Dec;101(12):2830-2840. doi: 10.1097/TP.0000000000001933. PMID: 28885497; PMCID: PMC5709200. |
| In vitro protocol: | 1. Li S, Sheng J, Liu Z, Fan Y, Zhang C, Lv T, Hu S, Jin J, Yu W, Song Y. Potent antitumour of the mTORC1/2 dual inhibitor AZD2014 in docetaxel-sensitive and docetaxel-resistant castration-resistant prostate cancer cells. J Cell Mol Med. 2021 Mar;25(5):2436-2449. doi: 10.1111/jcmm.16155. Epub 2021 Jan 28. PMID: 33507584; PMCID: PMC7933970. 2. Kim HK, Kim SY, Lee SJ, Kang M, Kim ST, Jang J, Rath O, Schueler J, Lee DW, Park WY, Kim SJ, Park SH, Lee J. BEZ235 (PIK3/mTOR inhibitor) Overcomes Pazopanib Resistance in Patient-Derived Refractory Soft Tissue Sarcoma Cells. Transl Oncol. 2016 Jun;9(3):197-202. doi: 10.1016/j.tranon.2016.03.008. Epub 2016 May 12. PMID: 27267837; PMCID: PMC4907899. |
| In vivo protocol: | 1. Jones AT, Yang J, Narov K, Henske EP, Sampson JR, Shen MH. Allosteric and ATP-Competitive Inhibitors of mTOR Effectively Suppress Tumor Progression-Associated Epithelial-Mesenchymal Transition in the Kidneys of Tsc2+/- Mice. Neoplasia. 2019 Aug;21(8):731-739. doi: 10.1016/j.neo.2019.05.003. Epub 2019 Jun 14. PMID: 31207499; PMCID: PMC6580094. 2. Fantus D, Dai H, Ono Y, Watson A, Yokota S, Mohib K, Yoshida O, Ross MA, Watkins SC, Ramaswami B, Valusjkikh A, Rothstein DM, Thomson AW. Influence of the Novel ATP-Competitive Dual mTORC1/2 Inhibitor AZD2014 on Immune Cell Populations and Heart Allograft Rejection. Transplantation. 2017 Dec;101(12):2830-2840. doi: 10.1097/TP.0000000000001933. PMID: 28885497; PMCID: PMC5709200. |
1: Huo HZ, Zhou ZY, Wang B, Qin J, Liu WY, Gu Y. Dramatic suppression of colorectal cancer cell growth by the dual mTORC1 and mTORC2 inhibitor AZD-2014. Biochem Biophys Res Commun. 2014 Jan 10;443(2):406-12. doi: 10.1016/j.bbrc.2013.11.099. Epub 2013 Dec 2. PubMed PMID: 24309100.
2: Kahn J, Hayman TJ, Jamal M, Rath BH, Kramp T, Camphausen K, Tofilon PJ. The mTORC1/mTORC2 inhibitor AZD2014 enhances the radiosensitivity of glioblastoma stem-like cells. Neuro Oncol. 2014 Jan;16(1):29-37. doi: 10.1093/neuonc/not139. Epub 2013 Dec 4. PubMed PMID: 24311635; PubMed Central PMCID: PMC3870843.
3: Rastogi R, Jiang Z, Ahmad N, Rosati R, Liu Y, Beuret L, Monks R, Charron J, Birnbaum MJ, Samavati L. Rapamycin induces mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) expression through activation of protein kinase B and mitogen-activated protein kinase kinase pathways. J Biol Chem. 2013 Nov 22;288(47):33966-77. doi: 10.1074/jbc.M113.492702. Epub 2013 Oct 14. PubMed PMID: 24126911; PubMed Central PMCID: PMC3837136.
4: Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett. 2013 Mar 1;23(5):1212-6. doi: 10.1016/j.bmcl.2013.01.019. Epub 2013 Jan 18. PubMed PMID: 23375793.
