Vistusertib | AZD-2014 | CAS#1009298-59-2 | mTOR Inhibitor

MedKoo Cat#: 204520 | Name: Vistusertib (AZD-2014)

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

Vistusertib (AZD-2014)

CAS#1009298-59-2

Theoretical Analysis

MedKoo Cat#: 204520

Name: Vistusertib (AZD-2014)

CAS#: 1009298-59-2

Chemical Formula: C25H30N6O3

Exact Mass: 462.2379

Molecular Weight: 462.54

Elemental Analysis: C, 64.92; H, 6.54; N, 18.17; O, 10.38

Price and Availability

Size	Price	Availability
5mg	USD 90.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 400.00	Ready to ship
100mg	USD 650.00	Ready to ship
200mg	USD 1,050.00	Ready to ship
500mg	USD 2,150.00	Ready to ship

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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

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#CRB40225

View CoA: current batch, Lot#CRB51228

QC Data

View QC data: current batch, Lot#CRB40225

View QC data: current batch, Lot#CRB51228

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMSO	47.7	103.06
	DMF	10.0	21.62
	Ethanol	0.5	1.08

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

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:

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: Sztankovics D, Szalai F, Moldvai D, Dankó T, Nagy N, Pápay J, Khoór A, Krencz I, Sebestyén A. Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression. Eur J Cell Biol. 2024 Dec;103(4):151468. doi: 10.1016/j.ejcb.2024.151468. Epub 2024 Nov 19. PMID: 39571513. 2: Feng Y, Jiang Q, Ma X, Sun H, Chai Y, Li X, Wang Z, Feng F. Photosensitizing metal-organic framework nanoparticles combined with tumor-sensitization strategies can enhance the phototherapeutic effect upon medullary thyroid carcinoma. Biochim Biophys Acta Gen Subj. 2024 Dec;1868(12):130725. doi: 10.1016/j.bbagen.2024.130725. Epub 2024 Oct 19. PMID: 39433228. 3: Shaikh TB, Chandra Y, Andugulapati SB, Sistla R. Vistusertib improves pulmonary inflammation and fibrosis by modulating inflammatory/oxidative stress mediators via suppressing the mTOR signalling. Inflamm Res. 2024 Jul;73(7):1223-1237. doi: 10.1007/s00011-024-01894-5. Epub 2024 May 24. PMID: 38789791. 4: Gil-Sierra MD, Briceño-Casado MDP, Moreno-Ramos C. Biomarker Analysis of Vistusertib Plus Paclitaxel Regimen. JAMA Oncol. 2023 Nov 1;9(11):1585-1586. doi: 10.1001/jamaoncol.2023.3398. PMID: 37676676. 5: Giannone G, McNeish IA, Banerjee S. Biomarker Analysis of Vistusertib Plus Paclitaxel Regimen-Reply. JAMA Oncol. 2023 Nov 1;9(11):1586-1587. doi: 10.1001/jamaoncol.2023.3401. PMID: 37676655. 6: Wang T, Jin C, Jiang W, Zhao T, Xu Y, Li H. Determination of five mTOR inhibitors in human plasma for hepatocellular carcinoma treatment using QuEChERS-UHPLC-MS/MS. J Pharm Biomed Anal. 2023 Oct 25;235:115652. doi: 10.1016/j.jpba.2023.115652. Epub 2023 Aug 19. PMID: 37633163. 7: Fan C, Wunderlich M, Cai X, Yan Z, Zhang F, Davis AK, Xu L, Guo F, Lu QR, Azam M, Tian W, Zheng Y. Kinase-independent role of mTOR and on-/off-target effects of an mTOR kinase inhibitor. Leukemia. 2023 Oct;37(10):2073-2081. doi: 10.1038/s41375-023-01987-w. Epub 2023 Aug 2. PMID: 37532788. 8: Jordan JT, Orr CC, Thalheimer RD, Cambillo JV, Beauchamp RL, Shaikh G, Muzikansky A, Stemmer-Rachamimov A, Giovannini M, Kalamarides M, Barker FG 2nd, Ramesh V, Plotkin SR. Prospective phase II trial of the dual mTORC1/2 inhibitor vistusertib for progressive or symptomatic meningiomas in persons with neurofibromatosis 2. Neurooncol Adv. 2023 Apr 17;5(1):vdad041. doi: 10.1093/noajnl/vdad041. PMID: 37215956; PMCID: PMC10195194. 9: Banerjee S, Giannone G, Clamp AR, Ennis DP, Glasspool RM, Herbertson R, Krell J, Riisnaes R, Mirza HB, Cheng Z, McDermott J, Green C, Kristeleit RS, George A, Gourley C, Lewsley LA, Rai D, Banerji U, Hinsley S, McNeish IA. Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma: The OCTOPUS Multicenter, Phase 2, Randomized Clinical Trial. JAMA Oncol. 2023 May 1;9(5):675-682. doi: 10.1001/jamaoncol.2022.7966. Erratum in: JAMA Oncol. 2023 Aug 1;9(8):1155. doi: 10.1001/jamaoncol.2023.1907. PMID: 36928279; PMCID: PMC10020933. 10: Mourksi NE, Dalban C, Colombe-Vermorel A, Odeyer L, Simioni V, Frenel JS, Fabbro M, Bazan F, Abadie-Lacourtoisie S, Coquan E, Martinez S, Garin G, Tabone- Eglinger S, Treilleux I, Chabaud S, Pérol D, Ray-Coquard I, Heudel PE, Diaz JJ, Marcel V. Ribosome biogenesis-based predictive biomarkers in endocrine therapy (Anastrozole) combined with mTOR inhibitor (Vistusertib) in endometrial cancer: translational study from the VICTORIA trial in collaboration with the GINECO group. Mol Oncol. 2023 Jan;17(1):27-36. doi: 10.1002/1878-0261.13340. Epub 2022 Dec 7. PMID: 36370117; PMCID: PMC9812831. 11: Barlesi F, Tomasini P, Karimi M, Michiels S, Raimbourg J, Daniel C, Janicot H, Madroszyk A, Audigier-Valette C, Quoix E, Mazieres J, Moro-Sibilot D, Dansin E, Molinier O, Morel H, Pichon E, Cortot A, Otto J, Chomy F, Souquet PJ, Cloarec N, Giroux-Leprieur E, Bieche I, Lacroix L, Boyault S, Attignon V, Soubeyran I, Morel A, Tran-Dien A, Jacquet A, Dall'Olio FG, Jimenez M, Soria JC, Besse B. Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase II Randomized SAFIR02-Lung/IFCT 1301 Trial. Clin Cancer Res. 2022 Sep 15;28(18):4018-4026. doi: 10.1158/1078-0432.CCR-22-0371. PMID: 35802649. 12: Tang W, Zhou J, Yang W, Feng Y, Wu H, Mok MTS, Zhang L, Liang Z, Liu X, Xiong Z, Zeng X, Wang J, Lu J, Li J, Sun H, Tian X, Yeung PC, Hou Y, Lee HM, Lam CCH, Leung HHW, Chan AWH, To KF, Wong J, Lai PBS, Ng KKC, Wong SKH, Wong VWS, Kong APS, Sung JJY, Cheng ASL. Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver. Cell Mol Immunol. 2022 Jul;19(7):834-847. doi: 10.1038/s41423-022-00872-3. Epub 2022 May 20. PMID: 35595819; PMCID: PMC9243114. 13: Combination Vistusertib and Anastrozole Shows Benefit in Endometrial Cancer. Cancer Discov. 2022 Jul 6;12(7):OF20. doi: 10.1158/2159-8290.CD-RW2022-093. PMID: 35593584. 14: Heudel P, Frenel JS, Dalban C, Bazan F, Joly F, Arnaud A, Abdeddaim C, Chevalier-Place A, Augereau P, Pautier P, Chakiba C, You B, Lancry-Lecomte L, Garin G, Marcel V, Diaz JJ, Treilleux I, Pérol D, Fabbro M, Ray-Coquard I. Safety and Efficacy of the mTOR Inhibitor, Vistusertib, Combined With Anastrozole in Patients With Hormone Receptor-Positive Recurrent or Metastatic Endometrial Cancer: The VICTORIA Multicenter, Open-label, Phase 1/2 Randomized Clinical Trial. JAMA Oncol. 2022 Jul 1;8(7):1001-1009. doi: 10.1001/jamaoncol.2022.1047. PMID: 35551299; PMCID: PMC9100474. 15: Liao H, Wang Y, Xu X, Zhou C, Zhang J, Zhong K, Yang D. [The dual mTORC1/2 inhibitor AZD2014 inhibits acute graft rejection in a rat liver transplantation model]. Nan Fang Yi Ke Da Xue Xue Bao. 2022 Apr 20;42(4):598-603. Chinese. doi: 10.12122/j.issn.1673-4254.2022.04.17. PMID: 35527497; PMCID: PMC9085585. 16: Choudhury AD, Higano CS, de Bono JS, Cook N, Rathkopf DE, Wisinski KB, Martin-Liberal J, Linch M, Heath EI, Baird RD, García-Carbacho J, Quintela- Fandino M, Barry ST, de Bruin EC, Colebrook S, Hawkins G, Klinowska T, Maroj B, Moorthy G, Mortimer PG, Moschetta M, Nikolaou M, Sainsbury L, Shapiro GI, Siu LL, Hansen AR. A Phase I Study Investigating AZD8186, a Potent and Selective Inhibitor of PI3Kβ/δ, in Patients with Advanced Solid Tumors. Clin Cancer Res. 2022 Jun 1;28(11):2257-2269. doi: 10.1158/1078-0432.CCR-21-3087. PMID: 35247924; PMCID: PMC9662946. 17: Pinker B, Barciszewska AM. mTOR Signaling and Potential Therapeutic Targeting in Meningioma. Int J Mol Sci. 2022 Feb 10;23(4):1978. doi: 10.3390/ijms23041978. PMID: 35216092; PMCID: PMC8876623. 18: Scott SC, Anders NM, Scardina M, Hann CL, Rudek MA. Validation of a rapid liquid chromatography tandem mass spectrometric method for the quantitative analysis of vistusertib. J Pharm Biomed Anal. 2022 Jan 20;208:114436. doi: 10.1016/j.jpba.2021.114436. Epub 2021 Oct 22. PMID: 34735991; PMCID: PMC8693366. 19: Pi R, Yang Y, Hu X, Li H, Shi H, Liu Y, Wang X, Tong A, Lu T, Wei Y, Zhao X, Wei X. Dual mTORC1/2 inhibitor AZD2014 diminishes myeloid-derived suppressor cells accumulation in ovarian cancer and delays tumor growth. Cancer Lett. 2021 Dec 28;523:72-81. doi: 10.1016/j.canlet.2021.09.017. Epub 2021 Sep 21. PMID: 34560229. 20: Morscher RJ, Brard C, Berlanga P, Marshall LV, André N, Rubino J, Aerts I, De Carli E, Corradini N, Nebchi S, Paoletti X, Mortimer P, Lacroix L, Pierron G, Schleiermacher G, Vassal G, Geoerger B. First-in-child phase I/II study of the dual mTORC1/2 inhibitor vistusertib (AZD2014) as monotherapy and in combination with topotecan-temozolomide in children with advanced malignancies: arms E and F of the AcSé-ESMART trial. Eur J Cancer. 2021 Nov;157:268-277. doi: 10.1016/j.ejca.2021.08.010. Epub 2021 Sep 17. PMID: 34543871.