TAK-733

Catalog No.S2617

TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1.

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TAK-733 Chemical Structure

TAK-733 Chemical Structure
Molecular Weight: 504.23

Validation & Quality Control

3 customer reviews :

Quality Control & MSDS

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Product Description

Biological Activity

Description TAK-733 is a potent and selective MEK allosteric site inhibitor for MEK1 with IC50 of 3.2 nM, inactive to Abl1, AKT3, c-RAF, CamK1, CDK2, c-Met, etc. Phase 1.
Targets MEK1 [1]
IC50 3.2 nM
In vitro TAK-733 is highly potent and selective MEK allosteric site inhibitor with IC50 of 3.2 nM. TAK-733 shows potent enzymatic and cell activity with an EC50 of 1.9 nM against ERK phosphorylation in cells. [1]
In vivo TAK-733 demonstrates broad antitumor activity in mouse xenograft models of human cancer including models of melanoma, colorectal, NSCLC, pancreatic and breast cancer. TAK-733 is well tolerated with pharmacokinetics and pharmacodynamics that support once-daily oral dosing in humans. [1] TAK-733 shows maximally efficacious doses at once daily orally doses of 10 mg/kg. [2]
Features

Protocol(Only for Reference)

Animal Study: [2]

Animal Models Human solid tumor xenograft models including NSCLC (NCI H23 [KRAS and LKB1 mutations]), CRC (SW620 [KRAS, APC, p53 mutations]) Pancreatic cancer (Panc 1 and Capan 1 [KRAS mutations] and BxPC-3 [No MAPK mutations]) models in immunocompromised mice.
Formulation Saline
Dosages 10 mg/kg
Administration Orally administrated once daily for 21 days

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Qing Dong, et al. Bioorg Med Chem Lett, 2011, 21(5), 1315-1319.

[2] Fabrey R, et al. AACR Annual Meeting, 2012, Abs 3739.

Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT01613261 Withdrawn Advanced Nonhematologic Malignancies Millennium Pharmaceuticals, Inc. August 2013 Phase 1
NCT00948467 Completed Advanced Non-hematologic Malignancies|Advanced Metastatic Melanoma Millennium Pharmaceuticals, Inc. December 2009 Phase 1

Chemical Information

Download TAK-733 SDF
Molecular Weight (MW) 504.23
Formula

C17H15F2IN4O4

CAS No. 1035555-63-5
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms N/A
Solubility (25°C) * In vitro DMSO 101 mg/mL (200.3 mM)
Water <1 mg/mL (<1 mM)
Ethanol <1 mg/mL (<1 mM)
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
Chemical Name (R)-3-(2,3-dihydroxypropyl)-6-fluoro-5-(2-fluoro-4-iodophenylamino)-8-methylpyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione

Customer Product Validation(3)


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Rating
Source Dr.Wang from Southern Medical Hospital . TAK-733 purchased from Selleck
Method Western blot
Cell Lines A549 cells
Concentrations 0-10 uM
Incubation Time 2 h
Results Effect of MEK inhibitor TAK-733 in A549 cells. A549 cells were incubated with increasing concentrations of TAK-733 for 2 h. The cell lysates were harvested and phosphorylation of indicated proteins was determined by Western blotting.

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Rating
Source Jonas Nilsson, PhD from University of Gothenburg. TAK-733 purchased from Selleck
Method Western blot, cell apoptosis assays
Cell Lines Mouse carcinoma cells
Concentrations 1-1000 nM
Incubation Time 16/40 h
Results (A) whereas apoptosis was induced at 40h. (B) Biological effects of the compounds correlated with effects on phosphorylation of the MEK target ERK. (C) IC50 on S-phase and ERK-posphorylation: TAK-733=1-10 nM, GSK1120212=<1 nM.

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Rating
Source Dr. Zhang of Tianjin Medical University. TAK-733 purchased from Selleck
Method Western blot
Cell Lines T47D cells
Concentrations 0-10 μM
Incubation Time 3 h
Results Reduction of ERK1/2 phosphorylation in T47D cells treated with TAK-733 was observed.

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Tel: +1-832-582-8158 Ext:3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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