INK 128(MLN0128) (Synonyms: INK128; INK-128) |
Catalog No.GC10969
One-Click Copy Product Info
|
INK 128(MLN0128)(INK-128; MLN0128; TAK-228)은 mTOR 키나제에 대한 IC50이 1nM인 경구용 ATP 의존성 mTOR1/2 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1224844-38-5
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
INK 128 (MLN0128) is a selective inhibitor of mTOR with IC50 value of 1 nM [3].
mTOR (mammalian target of rapamycin) is an evolutionarily conserved serine/threonine kinase which combined PI3K/AKT/mTOR pathway and plays an important role in regulating many fundamental features of cell growth and division [1].
INK 128 (MLN0128) is a potent mTOR inhibitor. When tested with human pancreatic cancer cells, INK-128 treatment inhibited cell growth and survival via inhibiting mTOR in a time- and concentration- dependent manner [2]. In HER2-positive breast cell lines, INK 128 treatment significantly delayed cell cycle and inhibited cell proliferation through inhibiting mTOR [1].
In a ZR-75-1 breast cancer xenograft model, INK128 treatment in a dose of 0.3mg/Kg/day significantly inhibited tumor growth. When combined with other standard targeted therapy or chemotherapy such as sorafenib, sutent and paclitaxel, enhanced anti-tumor growth activity was observed. INK128 is reported to have excellent physiochemical properties and is currently undergoing preclinical evaluation [3]. When tested with MDA-MB361 mouse model, administration of INK 128 showed a resistance after 20 days, and combined with lapatinib resulted in long-lasting tumor regression [1].
References:
[1]. Garcia-Garcia, C., et al., Dual mTORC1/2 and HER2 blockade results in antitumor activity in preclinical models of breast cancer resistant to anti-HER2 therapy. Clin Cancer Res, 2012. 18(9): p. 2603-12.
[2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8.
[3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009.
| Kinase experiment [1]: | |
|
Kinase assays |
mTOR activity was assayed using LanthaScreen Kinase kit reagents. PI(3)K α, β, γ and δ activity were assayed using the PI(3)KHTRF assay kit. The concentration of INK 128 necessary to achieve inhibition of enzyme activity by 50% (IC50) was calculated using concentrations ranging from 20 μM to 0.1 nM (12-point curve). IC50 values were determined using a nonlinear regression model. |
| Cell experiment [2]: | |
|
Cell lines |
PANC-1 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 |
10 ~ 100 nM; 72 hrs |
|
Applications |
INK 128 time- and dose-dependently inhibited the survival of PANC-1 cells, and significantly reduced the viability of PANC-1 cells at the concentrations of 10 ~ 100 nM. There was no significant viability decrease until 48 hrs after INK 128 treatment. |
| Animal experiment [3]: | |
|
Animal models |
A ZR-75-1 breast cancer xenograft model |
|
Dosage form |
0.3 mg/kg/day; p.o. |
|
Applications |
In a ZR-75-1 breast cancer xenograft model, INK 128 significantly inhibited tumor growth. The combination therapy of INK 128 and other standard targeted therapy or chemotherapy such as Sorafenib, Sutent and Paclitaxel enhanced anti-tumor growth activity. |
|
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]. Hsieh AC, Liu Y, Edlind MP, Ingolia NT, Janes MR, Sher A, Shi EY, Stumpf CR, Christensen C, Bonham MJ, Wang S, Ren P, Martin M, Jessen K, Feldman ME, Weissman JS, Shokat KM, Rommel C, Ruggero D. The translational landscape of mTOR signalling steers cancer initiation and metastasis. Nature. 2012 Feb 22;485(7396):55-61. [2]. Lou, H.Z., et al., The novel mTORC1/2 dual inhibitor INK-128 suppresses survival and proliferation of primary and transformed human pancreatic cancer cells. Biochem Biophys Res Commun, 2014. 450(2): p. 973-8. [3]. Jessen K, et al. INK128 is a potent and selective TORC1/2 inhibitor with broad oral anti-tumor activity. AACR 2009 Molecular targets and cancer therapeutics meeting poster; Boston: 2009. |
|
| Cas No. | 1224844-38-5 | SDF | |
| Synonyms | INK128; INK-128 | ||
| Chemical Name | 5-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine | ||
| Canonical SMILES | CC(C)N1C2=C(C(=N1)C3=CC4=C(C=C3)OC(=N4)N)C(=NC=N2)N | ||
| Formula | C15H15N7O | M.Wt | 309.33 |
| Solubility | ≥ 15.45mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.2328 mL | 16.164 mL | 32.3279 mL |
| 5 mM | 646.6 μL | 3.2328 mL | 6.4656 mL |
| 10 mM | 323.3 μL | 1.6164 mL | 3.2328 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 37 reference(s) in Google Scholar.)