Takinib

Catalog No.S8663 Batch:S866301

Technical Data

Formula

C₁₈H₁₈N₄O₂

Molecular Weight

322.36

CAS No.

1111556-37-6

Solubility (25°C)*

In vitro

DMSO

30 mg/mL (93.06 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution	5% DMSO 1 95% Corn oil	0.37mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 7.4 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.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	0.37mg/ml	Taking the 1 mL working solution as an example, add 50 μL of 7.4 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.

* <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.)

Preparing Stock Solutions

Biological Activity

Description

Takinib is a potent and selective TAK1 inhibitor with an IC50 of 9.5 nM, more than 1.5 log more potent than the second and third ranked targets, IRAK4 (120 nM) and IRAK1 (390 nM), respectively. Takinib induces apoptosis.

Targets

TAK1 ^[1] (Cell-free assay)	IRAK4 ^[1] (Cell-free assay)	IRAK1 ^[1] (Cell-free assay)
9.5 nM	120 nM	390 nM

In vitro

Takinib is an inhibitor of autophosphorylated and non-phosphorylated TAK1 that binds within the ATP-binding pocket and inhibits by slowing down the rate-limiting step of TAK1 activation. At 10 μM, Takinib shows significant inhibitory activity (<10% enzyme activity after exposure) on six serine/threonine kinases, including TAK1, IRAK4, IRAK1, GCK, CLK2, and MINK1. TAK1/MAP3K7 is most potently inhibited with a half maximal inhibitory concentration (IC50) value of 9.5 nM. In cell models of rheumatoid arthritis and metastatic breast cancer, Takinib treatment results in TNF-a-dependent induction of apoptosis due to inhibition of TAK1 as a key switch between survival and cell death. Takinib does not inhibit any of the MAP2Ks or MAP3Ks family members, i.e., MKK6/MAP2K6, MEKK1/ MAP3K1, MKK1/MAP2K1. Takinib also shows no efficacy toward the TAK1-closely related MAP3K5/ASK1. Takinib potently and selectively targets TAK1 and induces apoptosis in TNF-a-stimulated breast cancer and RA in vitro models^[1].

In vivo

Takinib slows tumor growth in the Hodgkin lymphoma xenograft NSG mice.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines MDA-MB-231 cells Concentrations -- Incubation Time 24 h Method MDA-MB-231 cells (1,000 cells/well) are seeded in a 96-well plate with 10% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium. After 24h, cells are serum starved with 1% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium for 4h. Cells are treated with titrations of Takinib in the presence or absence of 30 ng/mL TNFa. Plates at 0h and 24h following treatment were frozen at -80℃ after removal of media. After 24h, 100 μl ddH2O is added to each well and plates are refrozen. 1 μl from Hoechst stock [1 mg/ml in 1:4 DMSO/H2O] is dissolved in 1 ml of TNE buffer (10mM Tris, 2M NaCl, 1 mM Na2EDTA) and 100 μl of this solution is added to each well. The fluorescence is determined at 355/460 nm.
Animal Study:^{^[2]}	Animal Models Female NSG mice Dosages 50 mg/kg Administration p.o.

Cell Assay:^{^[1]}

Cell lines
MDA-MB-231 cells
Concentrations
--
Incubation Time
24 h
Method
MDA-MB-231 cells (1,000 cells/well) are seeded in a 96-well plate with 10% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium. After 24h, cells are serum starved with 1% FBS, 5% Pen/Strep, 4g/l glucose DMEM medium for 4h. Cells are treated with titrations of Takinib in the presence or absence of 30 ng/mL TNFa. Plates at 0h and 24h following treatment were frozen at -80℃ after removal of media. After 24h, 100 μl ddH2O is added to each well and plates are refrozen. 1 μl from Hoechst stock [1 mg/ml in 1:4 DMSO/H2O] is dissolved in 1 ml of TNE buffer (10mM Tris, 2M NaCl, 1 mM Na2EDTA) and 100 μl of this solution is added to each well. The fluorescence is determined at 355/460 nm.

Animal Study:^{^[2]}

Animal Models
Female NSG mice
Dosages
50 mg/kg
Administration
p.o.

References

Selleck's Takinib has been cited by 9 publications

In vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma [ Nat Commun, 2023, 14(1):143]	PubMed: 36650150
Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway [ Front Immunol, 2023, 14:1266315]	PubMed: 38035075
ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses [ Cells, 2023, 12(23)2696]	PubMed: 38067124
TAK1 Reduces Surgery-induced Overactivation of RIPK1 to Relieve Neuroinflammation and Cognitive Dysfunction in Aged Rats [ Neurochem Res, 2023, 10.1007/s11064-023-03959-z]	PubMed: 37329446
Androgen Receptor Regulation in Prostate Stroma [ THE UNIVERSITY OF ARIZONA, 2023, ]	PubMed: none
FAK mediates LPS-induced inflammatory lung injury through interacting TAK1 and activating TAK1-NFκB pathway [ Cell Death Dis, 2022, 13(7):589]	PubMed: 35803916
Inhibition of Protein Synthesis Induced by CHK1 Inhibitors Discriminates Sensitive from Resistant Cancer Cells [ ACS Pharmacol Transl Sci, 2021, 4(4):1449-1461]	PubMed: 34423276
A role for SHARPIN in platelet linear protein ubiquitination and function [ bioRxiv, 2021, 10.1101/2021.01.13.426403]	PubMed: None
TGFβR-SMAD3 Signaling Induces Resistance to PARP Inhibitors in the Bone Marrow Microenvironment [ Cell Rep, 2020, 33(1):108221]	PubMed: 33027668

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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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