WH-4-023

Catalog No.S7565 Batch:S756502

Technical Data

Formula

C₃₂H₃₆N₆O₄

Molecular Weight

568.67

CAS No.

837422-57-8

Solubility (25°C)*

In vitro

DMSO

100 mg/mL (175.84 mM)

Water

Insoluble

Ethanol

Insoluble

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

Clear solution

5%DMSO 1 30%PEG300 2 5%Tween80 3 60%ddH2O

1.0mg/ml

Taking the 1 mL working solution as an example, add 50 μL 20 mg/ml clarified DMSO stock solution to 300 μL PEG300, mix evenly to clarify it; add 50 μL Tween80 to the above system, mix evenly to clarify it; then continue to add 600 μL 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

WH-4-023 (KIN001-112, KIN112, Dual LCK/SRC inhibitor) is a potent and orally active Lck/Src inhibitor with IC50s of 2 nM and 6 nM in cell-free assays, respectively. Exhibits >300-fold selectivity against p38α and KDR. Also potently inhibits SIK (IC50 values are 10, 22 and 60 nM for SIK 1, 2 and 3 respectively) and displays selectivity over a range of closely related kinases.

Targets

Lck ^[1] (Cell-free assay)	Src ^[1] (Cell-free assay)
2 nM	6 nM

In vitro

WH-4-023 shows little activity on p38 and KDR. ^[1]

Protocol (from reference)

Kinase Assay:^{^[1]}	Lck Kinase Assay The Lck HTRF kinase assay involves ATP-dependent phosphorylation of a biotinylated substrate peptide of gastrin in the presence or absence of inhibitor compound. The final concentration of gastrin is 1.2 μM. The final concentration of ATP is 0.5 μM (Km app = 0.6 ± 0.1 μM), and the final concentration of Lck (a GST-kinase domain fusion (AA 225−509)) is 250 pM. Buffer conditions are as follows: 50 mM HEPES pH = 7.5, 50 mM NaCl, 20 mM MgCl₂, 5 mM MnCl, 2 mM DTT, 0.05% BSA. The assay is quenched and stopped with 160 μL of detection reagent. Detection reagents are as follows: Buffer made of 50 mM Tris, pH = 7.5, 100 mM NaCl, 3 mM EDTA, 0.05% BSA, 0.1% Tween20. Prior to reading, Streptavidin allophycocyanin (SA-APC) is added at a final concentration in the assay of 0.0004 mg/mL, along with europilated anti-phosphotyrosine Ab (Eu-anti-PY) at a final conc of 0.025 nM. The assay plate is read in a Discovery fluorescence plate reader with excitation at 320 nm and emission at 615 and 655 nm. Assays for other kinases are done in a similar way as described above, varying the concentrations of enzyme, peptide substrate, and ATP added to the reaction, depending on the specific activity of the kinase and measured Kms for the substrates.
Animal Study:^{^[3]}	Animal Models C57BL/6 mice Dosages 100 mg/kg Administration i.v.

Kinase Assay:^{^[1]}

Lck Kinase Assay
The Lck HTRF kinase assay involves ATP-dependent phosphorylation of a biotinylated substrate peptide of gastrin in the presence or absence of inhibitor compound. The final concentration of gastrin is 1.2 μM. The final concentration of ATP is 0.5 μM (Km app = 0.6 ± 0.1 μM), and the final concentration of Lck (a GST-kinase domain fusion (AA 225−509)) is 250 pM. Buffer conditions are as follows: 50 mM HEPES pH = 7.5, 50 mM NaCl, 20 mM MgCl₂, 5 mM MnCl, 2 mM DTT, 0.05% BSA. The assay is quenched and stopped with 160 μL of detection reagent. Detection reagents are as follows: Buffer made of 50 mM Tris, pH = 7.5, 100 mM NaCl, 3 mM EDTA, 0.05% BSA, 0.1% Tween20. Prior to reading, Streptavidin allophycocyanin (SA-APC) is added at a final concentration in the assay of 0.0004 mg/mL, along with europilated anti-phosphotyrosine Ab (Eu-anti-PY) at a final conc of 0.025 nM. The assay plate is read in a Discovery fluorescence plate reader with excitation at 320 nm and emission at 615 and 655 nm. Assays for other kinases are done in a similar way as described above, varying the concentrations of enzyme, peptide substrate, and ATP added to the reaction, depending on the specific activity of the kinase and measured Kms for the substrates.

Animal Study:^{^[3]}

Animal Models
C57BL/6 mice
Dosages
100 mg/kg
Administration
i.v.

References

Customer Product Validation

: Data from [Data independently produced by , , Blood, 2017, 130(25):2750-2761]

Selleck's WH-4-023 has been cited by 20 publications

Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously [ Nat Commun, 2024, 15(1):668]	PubMed: 38253551
Establishment of porcine embryonic stem cells in simplified serum free media and feeder free expansion [ Stem Cell Res Ther, 2024, 15(1):245]	PubMed: 39113095
Generation of a humanized mesonephros in pigs from induced pluripotent stem cells via embryo complementation [ Cell Stem Cell, 2023, 30(9):1235-1245.e6]	PubMed: 37683604
Modeling human pregastrulation development by 3D culture of blastoids generated from primed-to-naïve transitioning intermediates [ Protein Cell, 2023, 14(5):337-349]	PubMed: 37155315
Short C-terminal Musashi-1 proteins regulate pluripotency states in embryonic stem cells [ Cell Rep, 2023, 42(10):113308]	PubMed: 37858462
Discordance between chromatin accessibility and transcriptional activity during the human primed-to-naïve pluripotency transition process [ Cell Regen, 2023, 10.1186/s13619-023-00179-2]	PubMed: 37938437
Generation and characterization of stable pig pregastrulation epiblast stem cell lines [ Cell Res, 2022, 32(4):383-400]	PubMed: 34848870
Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures [ Nat Commun, 2022, 13(1):3147]	PubMed: 35672317
Recapitulating early human development with 8C-like cells [ Cell Rep, 2022, 39(12):110994]	PubMed: 35732112
Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia [ Sci Adv, 2022, 8(49):eabq8437]	PubMed: 36490346

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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.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.