research use only

TAK-733 MEK inhibitor

Name: TAK-733
Brand: Selleck Chemicals
SKU: S2617
Availability: InStock
Rating: 5 (24 reviews)

Cat.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.

Chemical Structure

Molecular Weight: 504.23

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.76%

99.76

Related Targets	Ras ERK p38 MAPK Raf JNK S6 Kinase MAP4K TAK1 Mixed Lineage Kinase ASK MNK MAPKAPK2 KLF TOPK
Related Products	Mirdametinib (PD0325901) U0126-EtOH PD98059 PD184352 (CI-1040) BIX 02189 Pimasertib (AS-703026) Refametinib (RDEA119) AZD8330 BIX 02188 GDC-0623 SL-327 Myricetin BI-847325 PD318088 APS-2-79 HCl MEK1 Antibody [F9N7] PD184161 Nedometinib MEK1 Antibody [G24C19] GW284543 (UNC10225170) RO4987655 Atebimetinib (IMM-1-104) MEK1/2 Antibody [J11P23] Zapnometinib (PD0184264) Tunlametinib Phospho-MEK1/2 (Ser217/221) Antibody [G6P21] Rap1B Antibody [H22K21] MEK2 Antibody [M18L8] Rap1A/Rap1B Antibody [E5J15] MKK3 Antibody [E15H14]

Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	Activity Description	PMID
COLO205	Cytotoxicity assay	72 hrs	Cytotoxicity against human COLO205 cells after 72 hrs by MTS assay, EC50=0.0021μM.	21310613
A375	Cytotoxicity assay	72 hrs	Cytotoxicity against human A375 cells after 72 hrs by MTS assay, EC50=0.0031μM.	21310613
COLO205	Function assay		Inhibition of MEK1 in human COLO205 cells, IC50=0.00692μM.	24755426
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight	504.23	Formula	C₁₇H₁₅F₂IN₄O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	1035555-63-5	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CN1C2=C(C(=C(C1=O)F)NC3=C(C=C(C=C3)I)F)C(=O)N(C=N2)CC(CO)O

Solubility

In vitro
Batch:

DMSO : 101 mg/mL (200.3 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (9.92mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.710mg/ml (1.41mM)	Taking the 1 mL working solution as an example, add 50 μL of 14.2 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

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.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

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 ddH₂O, 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.

Mechanism of Action

Targets/IC₅₀/Ki	MEK1 ^[1] (Cell-free assay) 3.2 nM
In vitro	TAK-733 is highly potent and selective MEK allosteric site inhibitor with IC50 of 3.2 nM. This compound 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. This compound is well tolerated with pharmacokinetics and pharmacodynamics that support once-daily oral dosing in humans. ^[1] It shows maximally efficacious doses at once daily orally doses of 10 mg/kg. ^[2]
References	[1] https://pubmed.ncbi.nlm.nih.gov/21310613/ [2] http://cancerres.aacrjournals.org/cgi/content/short/72/8_MeetingAbstracts/3739

Applications

Methods	Biomarkers	Images	PMID
Growth inhibition assay	Cell viability		26918363
Western blot	p-ERK / p-AKT / p-S6R / p-GSK3 pRb / Cyclin E		26918363

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

Tech Support

Handling Instructions

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

If you have any other enquiries, please leave a message.

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):