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WH-4-023

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WH-4-023
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email: [email protected]        [email protected]

Cat #: V0670 CAS #: 837422-57-8 Purity ≥ 98%

Description: WH-4-023 (also called KIN112; WH-4023; KIN-001-112) is a novel, potent, selective and orally bioactive inhibitor of Src family kinase (dual Lck/Src inhibitor) with potential anti-inflammatory and anticancer activity. It inhibits dual Lck/Src kinases with IC50s of 2 nM and 6 nM in cell-free assays, respectively. WH-4-023 increased LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion.

References: [1]. Martin MW, et al. Novel 2-aminopyrimidine carbamates as potent and orally active inhibitors of Lck: synthesis, SAR, and in vivo antiinflammatory activity. J Med Chem. 2006 Aug 10;49(16):4981-91.

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Molecular Weight (MW)568.67
Molecular FormulaC32H36N6O4
CAS No.837422-57-8
Storage-20℃ for 3 years in powder formr
-80℃ for 2 years in solvent
Solubility In VitroDMSO: 12 mg/mL (21.1 mM)r
Water: <1 mg/mLr
Ethanol: 6 mg/mL (10.55 mM)
SMILES CodeO=C(OC1=C(C)C=CC=C1C)N(C2=CC=C(OC)C=C2OC)C3=NC(NC4=CC=C(N5CCN(C)CC5)C=C4)=NC=C3
SynonymsKIN001-112, KIN112; WH-4023; KIN-001-112, KIN-112; KIN 001-112, KIN 112; WH-4-023; WH4-023; WH 4-023; WH 4023; WH4023;
ProtocolIn VitroIn vitro activity: WH-4-023 inhibited a number of protein tyrosine kinases that possess a Thr residue at the gatekeeper site, such as FGF and Ephrin receptors, Src family members (Src, Lck, and Yes) and BTK. WH-4-023 also inhibited the SIKs and did not inhibit any other member of the AMPK-related kinase subfamily, which all possess a large hydrophobic residue (Met or Leu) at the gatekeeper site. WH-4-023 inhibited SIK 1, 2 and 3 with IC50 values of 10, 22 and 60 nM, respectively. Also, WH-4-023 increased LPS-stimulated IL-10 production and greatly suppressed proinflammatory cytokine secretion. 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 MnCl2, 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 Cell Assay: The purpose of this assay is to test the potency of T cell receptor (TCR; CD3) and CD28 signaling pathway inhibitors in human T cells. T cells are purified from human peripheral blood lymphocytes (hPBL) and preincubated with or without compound prior to stimulation with a combination of an anti-CD3 and an anti-CD28 antibody in 96-well tissue culture plates (1×105 T cells/well). Cells are cultured for ~20 h at 37°C in 5% CO2 and then secreted IL-2 in the supernatants is quantified by cytokine ELISA. The cells remaining in the wells are then pulsed with 3H-thymidine overnight to assess the T cell proliferative response. Cells are harvested onto glass fiber filters and 3H-thymidine incorporation into DNA is analyzed by liquid scintillation counter. For comparison purposes, phorbol myristic acid (PMA) and calcium ionophore are used in combination to induce IL-2 secretion from purified T cells. Potential inhibitor compounds are tested for inhibition of this response as described above for anti-CD3 and -CD28 antibodies. Human whole-blood anti-CD3/CD28-induced IL-2 secretion assays are run in a similar fashion as described above using whole blood from normal volunteers diluted 50% in tissue culture medium prior to stimulation
These protocols are for reference only. InvivoChem does not independently validate these methods.
Preparing Stock Solutions
Solvent volume to be added Mass (the weight of a compound)
Mother liquor concentration 1mg5mg10mg20mg
1mM1.7585 mL8.7924 mL17.5849 mL35.1698 mL
5mM0.3517 mL1.7585 mL3.5170 mL7.0340 mL
10mM0.1758 mL0.8792 mL1.7585 mL3.5170 mL
20mM0.0879 mL0.4396 mL0.8792 mL1.7585 mL
Quality Control Documentation
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