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| 10mg |
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| 25mg |
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Purity: ≥98%
WYE-687 is a novel, potent, ATP-competitive and selective inhibitor of mTOR (mammalian target of rapamycin) with potential antitumor activity. With an IC50 of 7 nM, it inhibits mTOR, and WYE687 demonstrated strong antiproliferative activity in vitro and high antitumor efficacy in vivo.
| Targets |
PI3K alpha (IC50 = 81 nM); PI3K gamma (IC50 = 3.11 μM); CDK2/CyclinE (IC50 = 430 nM); mTOR (IC50 = 7 nM); CK1 gamma1 (IC50 = 17.8 μM); p38 alpha (IC50 = 28.9 μM); mTORC1; mTORC2
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| ln Vitro |
WYE-687 inhibits recombinant mTOR enzyme with an IC50 of 7 nM in the DELFIA measuring His6-S6K1 T389 phosphorylation[1]. The MTT cell survival assay results show that WYE-687 potently inhibits HL-60 cell survival in a dose-dependent manner when applied concentrations of WYE-687 (33–1000 nM) are used to treat HL-60 AML cells. WYE-687 exhibits a time-dependent response as well. Following application of WYE-687 (100-1000 nM) treatment, the proportion of dead (“trypan blue” positive) HL-60 cells significantly increases. By using the [H3] Thymidine integration assay, the WYE-687 has also been shown to inhibit the proliferation of HL-60 cells. WYE-687 is also antisurvival (or "cytotoxic") to U937, THP-1, and AML-193 AML cell lines, according to the results[2].
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| ln Vivo |
U937 cells are inoculated into the flanks of SCID/beige mice. Mice are orally administered WYE-687 (5 or 25 mg/kg) daily for a total of 7 days when xenografted tumors have grown to a volume of about 100 mm3. The vehicle control, which consists of 5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400, is also given to the mice at this point. Based on results from prior experiments and related research, the WYE-687 regimen used in this study. The in vivo activity of WYE-687 is dose-dependent and significantly reduces the growth of the U937 xenograft tumor in SCID mice when administered at doses of 5 or 25 mg/kg per day. At day 15, the tumors that were treated with WYE-687 at doses of 5 mg/kg and 25 mg/kg were 50% and 75% smaller, respectively, than the tumors that were under the control of the vehicle. The tumor weights of mice receiving WYE-687 treatment are also noticeably lower than those of the vehicle group. With minimal toxicities, oral administration of WYE-687 significantly slows the growth of the U937 leukemic xenograft tumor in SCID mice[2].
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| Enzyme Assay |
The standard inhibitor assays are carried out in 96-well plates for 2 hours at room temperature using 25 L containing 6 nM Flag-TOR(3.5) (estimated 5-10% purity), 1 μM His6-S6K, and 100 μM ATP. DELFIA uses the Euphospho-p70S6K T389 antibody to carry out and detect the assays. A commercially purchased batch of mTOR is used in some assays. For the inhibitor versus ATP matrix competition, mTOR kinase reactions are carried out in the presence of different concentrations of ATP (0, 25, 50, 100, 200, 400, and 800 M) as well as different concentrations of inhibitor. The assays have 12 nM Flag-TOR(3.5) and 1 M His-S6K, and they take 30 minutes to complete. DELFIA similarly detects the assay results and processes them to produce double-reciprocal plots[1].
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| Cell Assay |
Acute myeloid leukemia (AML) cells and progenitor cells are plated onto 48-well tissue culture plates at a density of 1 ×105 cells/well in 0.5 mL DMEM containing 10% FBS. Cells are then treated with WYE-687 at the corresponding concentrations (33-1000 nM) in the presence of 1 mCi/mL of tritiated thymidine. Cells are washed, DNA is precipitated with cold 10% trichloroacetic acid (TCA), solubilized with 1.0 M sodium hydroxide, and aliquots are counted by liquid-scintillation spectrometry to determine [H3] thymidine incorporation. According to the value of the untreated control group, the treatment group's value is normalized[2].
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| Animal Protocol |
Mice: U937 cells(2×106 cells/mice, suspended in 100 mL of culture medium) are injected into the right flanks of 6-week-old male CB17 severe combined immunodeficient (SCID)/beige mice, and cells are allowed to develop into palpable tumors .
WYE-687 (5 mg/kg body weight), WYE-687 (25 mg/kg body weight), or the vehicle control (5% ethanol, 2% Tween 80, and 5% polyethylene glycol-400) are given to the animals when tumors have grown to a volume of about 100 mm3 in size. Freshly prepared doses of WYE-687 and vehicle control are administered daily for 7 days straight via oral gavage. We measure tumor sizes. When the experiment is finished, the animals are put to death, and the tumors are taken out and weighed.
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| References |
| Molecular Formula |
C28H32N8O3
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| Molecular Weight |
528.61
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| Exact Mass |
528.259
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| Elemental Analysis |
C, 63.62; H, 6.10; N, 21.20; O, 9.08
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| CAS # |
1062161-90-3
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| Related CAS # |
WYE-687 dihydrochloride;1702364-87-1
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| PubChem CID |
25229450
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| Appearance |
White solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
633.2±55.0 °C at 760 mmHg
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| Flash Point |
336.7±31.5 °C
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| Vapour Pressure |
0.0±1.9 mmHg at 25°C
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| Index of Refraction |
1.708
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| LogP |
1.36
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
39
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| Complexity |
785
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(OC)NC1=CC=C(C2=NC(N3CCOCC3)=C4C(N(C5CCN(CC6=CC=CN=C6)CC5)N=C4)=N2)C=C1
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| InChi Key |
VDOCQQKGPJENHJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H32N8O3/c1-38-28(37)31-22-6-4-21(5-7-22)25-32-26(35-13-15-39-16-14-35)24-18-30-36(27(24)33-25)23-8-11-34(12-9-23)19-20-3-2-10-29-17-20/h2-7,10,17-18,23H,8-9,11-16,19H2,1H3,(H,31,37)
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| Chemical Name |
methyl N-[4-[4-morpholin-4-yl-1-[1-(pyridin-3-ylmethyl)piperidin-4-yl]pyrazolo[3,4-d]pyrimidin-6-yl]phenyl]carbamate
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.73 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8918 mL | 9.4588 mL | 18.9175 mL | |
| 5 mM | 0.3784 mL | 1.8918 mL | 3.7835 mL | |
| 10 mM | 0.1892 mL | 0.9459 mL | 1.8918 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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mTOR kinase inhibitors profoundly inhibit cap-dependent and global protein synthesis in cancer cells. |
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