TCS 359

Catalog No.S8023 Batch:S802301

Technical Data

Formula	C₁₈H₂0N₂O₄S
Molecular Weight	360.43	CAS No.	301305-73-7
Solubility (25°C)*	In vitro	DMSO	15 mg/mL (41.61 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

TCS 359 is a potent FLT3 inhibitor with IC50 of 42 nM.

Targets

FLT3 ^[1]

42 nM

In vitro

TCS 359, a 2-acylaminothiophene-3-carboxamide, is a potent inhibitor of FLT3 with IC50 of 42 nM. TCS 359 inhibits MV4-11 proliferation with IC50 of 340 nM. TCS 359 is highly selective for FLT3 against a panel of kinases. ^[1]

Features

Highly potent and selective.

Protocol (from reference)

Kinase Assay:^{^[1]}	Affinity determination To determine the activity of the compounds of the present invention in an in vitro kinase assay, inhibition of the isolated kinase domain of the human FLT3 receptor is performed using the following fluorescence polarization (FP) protocol. The FLT3 fluorescence polarization assay utilizes the fluorescein-labeled phosphopeptide and the anti-phosphotyrosine antibody included in the Panvera Phospho-Tyrosine Kinase Kit. The FLT3 kinase reaction is incubated at room temperature for 30 min under the following conditions: 10 nM FLT3 571-993, 20μg/mL poly Glu4Tyr, 150μM ATP, 5 mM MgCl₂, and 1% compound in DMSO. The kinase reaction is stopped with the addition of EDTA. The fluorescein-labeled phosphopeptide and the anti-phosphotyrosine antibody are added and incubated for 30 min at room temperature and polarization is read.
Cell Assay:^{^[1]}	Cell lines MV4-11 Concentrations ~5 μM Incubation Time 72 hours Method MV4-11 cells are plated at 10,000 cells per well in 100 μL of in RPMI media containing penn/strep, 10% FBS, and 0.2 ng/mL GM-CSF. Compound dilutions or 0.1% DMSO (vehicle control) is added to cells and the cells are allowed to grow for 72 h at standard cell growth conditions. To measure total cell growth, an equal volume of CellTiterGlo reagent is added to each well and luminescence is quantified. Total cell growth is quantified as the difference in luminescent counts of cell number at Day 0 compared to total cell number at Day 3 (72 h of growth and/or compound treatment). All IC50 values are calculated in GraphPadPrism using non-linear regression analysis with a multiparameter (variable slope) equation.

Kinase Assay:^{^[1]}

Affinity determination
To determine the activity of the compounds of the present invention in an in vitro kinase assay, inhibition of the isolated kinase domain of the human FLT3 receptor is performed using the following fluorescence polarization (FP) protocol. The FLT3 fluorescence polarization assay utilizes the fluorescein-labeled phosphopeptide and the anti-phosphotyrosine antibody included in the Panvera Phospho-Tyrosine Kinase Kit. The FLT3 kinase reaction is incubated at room temperature for 30 min under the following conditions: 10 nM FLT3 571-993, 20μg/mL poly Glu4Tyr, 150μM ATP, 5 mM MgCl₂, and 1% compound in DMSO. The kinase reaction is stopped with the addition of EDTA. The fluorescein-labeled phosphopeptide and the anti-phosphotyrosine antibody are added and incubated for 30 min at room temperature and polarization is read.

Cell Assay:^{^[1]}

Cell lines
MV4-11
Concentrations
~5 μM
Incubation Time
72 hours
Method
MV4-11 cells are plated at 10,000 cells per well in 100 μL of in RPMI media containing penn/strep, 10% FBS, and 0.2 ng/mL GM-CSF. Compound dilutions or 0.1% DMSO (vehicle control) is added to cells and the cells are allowed to grow for 72 h at standard cell growth conditions. To measure total cell growth, an equal volume of CellTiterGlo reagent is added to each well and luminescence is quantified. Total cell growth is quantified as the difference in luminescent counts of cell number at Day 0 compared to total cell number at Day 3 (72 h of growth and/or compound treatment). All IC50 values are calculated in GraphPadPrism using non-linear regression analysis with a multiparameter (variable slope) equation.

References

[1] Raymond J. Patch, et al. Bioorg Med Chem Lett, 2006, 16(12), 3282-3286.

Selleck's TCS 359 has been cited by 2 publications

Inositol treatment inhibits medulloblastoma through suppression of epigenetic-driven metabolic adaptation [ Nat Commun, 2021, 12(1):2148]	PubMed: 33846320
Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6. [ Blood, 2016, 127(23):2890-90]	PubMed: 27099147

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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