WYE-354MTOR inhibitor,potent,ATP-competitive and cell-permeable CAS# 1062169-56-5 |
- AZD8055
Catalog No.:BCC3629
CAS No.:1009298-09-2
- Torin 1
Catalog No.:BCC3676
CAS No.:1222998-36-8
- XL388
Catalog No.:BCC2059
CAS No.:1251156-08-7
- LY 303511
Catalog No.:BCC1715
CAS No.:154447-38-8
- Rapamycin (Sirolimus)
Catalog No.:BCC3592
CAS No.:53123-88-9
- BEZ235 (NVP-BEZ235)
Catalog No.:BCC3655
CAS No.:915019-65-7
Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 1062169-56-5 | SDF | Download SDF |
PubChem ID | 44219749 | Appearance | Powder |
Formula | C24H29N7O5 | M.Wt | 495.53 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | WYE 354;WYE354 | ||
Solubility | DMSO : 6.67 mg/mL (13.46 mM; Need ultrasonic) | ||
Chemical Name | methyl 4-[6-[4-(methoxycarbonylamino)phenyl]-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate | ||
SMILES | COC(=O)NC1=CC=C(C=C1)C2=NC3=C(C=NN3C4CCN(CC4)C(=O)OC)C(=N2)N5CCOCC5 | ||
Standard InChIKey | IMXHGCRIEAKIBU-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C24H29N7O5/c1-34-23(32)26-17-5-3-16(4-6-17)20-27-21(29-11-13-36-14-12-29)19-15-25-31(22(19)28-20)18-7-9-30(10-8-18)24(33)35-2/h3-6,15,18H,7-14H2,1-2H3,(H,26,32) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
||
About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
||
Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | WYE-354 is a potent cell-permeable inhibitor of mTOR with IC50 value of 4.3 nM. | |||||
Targets | mTOR | |||||
IC50 | 4.3 nM |
Cell experiment [1]: | |
Cell lines | HEK293 cells |
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. |
Reacting condition | 1 h; 5 μM |
Applications | To test directly the inhibition of mTORC2 catalytic activity in vitro, we immunoprecipitated mTORC2 and mTORC1 from HEK293 cells and performed immune-complex kinase assay of the mTORC2-specific substrate His6-AKT or the mTORC1 substrate His6-S6K. AKT (S473) phosphorylation was dose dependently inhibited by WYE-354. |
Animal experiment [1]: | |
Animal models | BALB/c nu/nu female mice |
Dosage form | 50 mg/kg; intraperitoneal injection |
Application | Nude mice bearing the PTEN-null PC3MM2 tumors were administered i.p. with vehicle or 50 mg/kg WYE-354.Tumor lysates prepared at 1, 2, 4, and 6 hours after dosing were immunoblotted for levels of P-S6K(T389), P-AKT(S473), and P-AKT(T308). Quantification of the immunoblotting results indicated that WYE-354 completely inhibited P-S6K (T389) for at least 6 hours and substantially inhibited P-AKT(S473) for 6 hour. As expected, P-AKT(T308) in the same tumors was variably but not significantly inhibited. WYE-354 selectively inhibited P-AKT(S473) via targeting mTORC2. |
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] Yu K, Toral-Barza L, Shi C, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin[J]. Cancer research, 2009, 69(15): 6232-6240. |
WYE-354 Dilution Calculator
WYE-354 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.018 mL | 10.0902 mL | 20.1804 mL | 40.3608 mL | 50.451 mL |
5 mM | 0.4036 mL | 2.018 mL | 4.0361 mL | 8.0722 mL | 10.0902 mL |
10 mM | 0.2018 mL | 1.009 mL | 2.018 mL | 4.0361 mL | 5.0451 mL |
50 mM | 0.0404 mL | 0.2018 mL | 0.4036 mL | 0.8072 mL | 1.009 mL |
100 mM | 0.0202 mL | 0.1009 mL | 0.2018 mL | 0.4036 mL | 0.5045 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
Calcutta University
University of Minnesota
University of Maryland School of Medicine
University of Illinois at Chicago
The Ohio State University
University of Zurich
Harvard University
Colorado State University
Auburn University
Yale University
Worcester Polytechnic Institute
Washington State University
Stanford University
University of Leipzig
Universidade da Beira Interior
The Institute of Cancer Research
Heidelberg University
University of Amsterdam
University of Auckland
TsingHua University
The University of Michigan
Miami University
DRURY University
Jilin University
Fudan University
Wuhan University
Sun Yat-sen University
Universite de Paris
Deemed University
Auckland University
The University of Tokyo
Korea University
WYE-354 is a powerful and selective ATP-competitive kinase heterocyclic inhibitors with biochemical IC50 of 5 nM against mTOR.[1]
WYE-354 displays very specific selectivity to PI3K families (>100-fold to PI3K and >500-fold to PI3K), but it can’t inhibit some protein kinases. May cancer cell lines including MDA-MB-468 and U87MG can be inhibited by WYE-354 in 0.3–1 mM range.[1]
In-vitro study has proved that WYE-354 can inhibit substrate phosphorylation such as p-4E-BP1 T37/46 and p-Akt S473 by mTORC1 and mTORC2. WYE-354 can reduce Akt downstream function and block the propagation of the cancer cell lines with an IC50 value from sub-micromolar to micromolar range [3]. These effects were consistent with the G1 cell cycle arrest in two cell lines, including rapamycin-sensitive and rapamycin-resistant cells. It is believed to induce apoptosis, repress the global protein synthesis, and down-regulate many angiogenic factors.[3]
References:
[1] Qingsong Liu, Carson Thoreen, Jinhua Wang, David Sabatini, Nathanael S. Gray. mTOR mediated anti-cancer drug discovery. Drug Discovery Today. 2009. 6(2): 47-55.
[2] Shi-Yong Sun. mTOR kinase inhibitors as potential cancer therapeutic drugs. Cancer Letters. 28 October 2013. 340(1): 1-8.
- WYE-687
Catalog No.:BCC4604
CAS No.:1062161-90-3
- WAY-600
Catalog No.:BCC4607
CAS No.:1062159-35-6
- TC-G 1004
Catalog No.:BCC6165
CAS No.:1061747-72-5
- PND-1186
Catalog No.:BCC1866
CAS No.:1061353-68-1
- Senktide
Catalog No.:BCC6921
CAS No.:106128-89-6
- Hoechst 33342 analog 2
Catalog No.:BCC1631
CAS No.:106050-84-4
- Palmatine hydrochloride
Catalog No.:BCN5914
CAS No.:10605-02-4
- β-Interleukin I (163-171), human
Catalog No.:BCC1017
CAS No.:106021-96-9
- Nerol
Catalog No.:BCN8517
CAS No.:106-25-2
- Geraniol
Catalog No.:BCN2631
CAS No.:106-24-1
- 2-(3,4-Dihydroxyphenyl)ethanol
Catalog No.:BCN5871
CAS No.:10597-60-1
- Sulfocostunolide B
Catalog No.:BCN5870
CAS No.:1059671-65-6
- Ro3280
Catalog No.:BCC3962
CAS No.:1062243-51-9
- LDN-193189
Catalog No.:BCC3687
CAS No.:1062368-24-4
- ML347
Catalog No.:BCC5331
CAS No.:1062368-49-3
- LDN193189 Hydrochloride
Catalog No.:BCC1695
CAS No.:1062368-62-0
- Thioperamide
Catalog No.:BCC6734
CAS No.:106243-16-7
- 4-[(4-Methylpiperazin-1-yl) methyl]benzoic acid dihydrochloride
Catalog No.:BCC8669
CAS No.:106261-49-8
- Risperidone
Catalog No.:BCC3850
CAS No.:106266-06-2
- Sikokianin A
Catalog No.:BCN3133
CAS No.:106293-99-6
- Nomilin
Catalog No.:BCN1034
CAS No.:1063-77-0
- Rufinamide
Catalog No.:BCC5078
CAS No.:106308-44-5
- DAPTA
Catalog No.:BCC5909
CAS No.:106362-34-9
- ω-Conotoxin GVIA
Catalog No.:BCC5700
CAS No.:106375-28-4
Rapamycin and WYE-354 suppress human gallbladder cancer xenografts in mice.[Pubmed:26397134]
Oncotarget. 2015 Oct 13;6(31):31877-88.
Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients.
Autophagy inhibition sensitizes WYE-354-induced anti-colon cancer activity in vitro and in vivo.[Pubmed:27020593]
Tumour Biol. 2016 Sep;37(9):11743-11752.
Mammalian target of rapamycin (mTOR) complex 1 (mTORC1) and mTORC2 are frequently dysregulated in human colon cancers. In the present study, we evaluated the potential anti-colon cancer cell activity by a novel mTORC1/2 dual inhibitor WYE-354. We showed that WYE-354 was anti-survival and anti-proliferative when adding to primary (patient-derived) and established (HCT-116, HT-29, Caco-2, LoVo, and DLD-1 lines) colon cancer cells. In addition, WYE-354 treatment activated caspase-dependent apoptosis in the colon cancer cells. Mechanistically, WYE-354 blocked mTORC1 and mTORC2 activation. Meanwhile, it also induced autophagy activation in the colon cancer cells. Autophagy inhibitors (bafilomycin A1 and 3-methyladenine), or shRNA-mediated knockdown of autophagy elements (Beclin-1 and ATG-5), remarkably sensitized WYE-354-mediated anti-colon cancer cell activity in vitro. Further studies showed that WYE-354 administration inhibited HT-29 xenograft growth in severe combined immunodeficient (SCID) mice. Importantly, its activity in vivo was further potentiated with co-administration of the autophagy inhibitor 3-MA. Phosphorylations of Akt (Ser-473) and S6 were also decreased in WYE-354-treated HT-29 xenografts. Together, these pre-clinical results demonstrate the potent anti-colon cancer cell activity by WYE-354, and its activity may be further augmented with autophagy inhibition.