A 419259Lck inhibitor CAS# 364042-47-7 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 364042-47-7 | SDF | Download SDF |
PubChem ID | 6539952 | Appearance | Powder |
Formula | C29H34N6O | M.Wt | 482.62 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | RK-20449 | ||
Solubility | Soluble in Chloroform,Dichloromethane,Ethyl Acetate,DMSO,Acetone,etc. | ||
Chemical Name | 7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine | ||
SMILES | CN1CCN(CC1)C2CCC(CC2)N3C=C(C4=C3N=CN=C4N)C5=CC=C(C=C5)OC6=CC=CC=C6 | ||
Standard InChIKey | FDVSOQRNTAPCHB-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C29H34N6O/c1-33-15-17-34(18-16-33)22-9-11-23(12-10-22)35-19-26(27-28(30)31-20-32-29(27)35)21-7-13-25(14-8-21)36-24-5-3-2-4-6-24/h2-8,13-14,19-20,22-23H,9-12,15-18H2,1H3,(H2,30,31,32) | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | A 419259 is a broad-spectrum pyrrolo-pyrimidine inhibitor, designed to enhance selectivity towards the Src family with IC50 of 9 nM, <3 nM and <3 nM for Src, Lck and Lyn, respectively.In Vitro:A 419259 is a second-generation pyrrolo-pyrimidine designed to enhance selectivity towards the Src family relative to other cytoplasmic tyrosine kinases. A-419259 inhibits K-562 cells with an IC50 between 0.1 and 0.3 μM, and Meg-01 proliferation with an IC50 of approximately 0.1 μM. A-419259 also potently induces apoptosis in K-562 cells beginning at 0.1 μM and increasing in a dose-dependent manner. PP2 inhibits Src kinase autophosphorylation in both Ph+ cell lines (K-562 and Meg-01) with an IC50 between 3 and 10 μM, while A-419259 blocks kinase activation between 0.1 and 0.3 μM. A-419259 strongly inhibits DAGM/Bcr-Abl cell proliferation in the absence of IL-3 with an IC50 between 0.1 and 0.3 μM[1]. A-419259 is a broad-spectrum pyrrolo-pyrimidine inhibitor, and blocks proliferation and induces apoptosis in CML cell lines. A-419259 inhibits overall SFK activity in K562 and other CML cell lines with an IC50 value of 0.1-0.3 μM[2]. References: |
A 419259 Dilution Calculator
A 419259 Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.072 mL | 10.3601 mL | 20.7202 mL | 41.4405 mL | 51.8006 mL |
5 mM | 0.4144 mL | 2.072 mL | 4.144 mL | 8.2881 mL | 10.3601 mL |
10 mM | 0.2072 mL | 1.036 mL | 2.072 mL | 4.144 mL | 5.1801 mL |
50 mM | 0.0414 mL | 0.2072 mL | 0.4144 mL | 0.8288 mL | 1.036 mL |
100 mM | 0.0207 mL | 0.1036 mL | 0.2072 mL | 0.4144 mL | 0.518 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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A 419259 is an orally available inhibitor of lck with IC50 value of 15nM [1].
Lck is a src family tyrosine kinase. Inhibition of this enzyme results in a prevention of T-cell activation and provides an application for treating T-cell dependent processes such as autoimmune and inflammatory diseases. A 419259 is screened out by its potent inhibitory activity against the recombinant lck (64–509) with IC50 value of 15nM. It is also a selective inhibitor. It shows inactive against a panel of other kinases including cMet, IGFR, PKC and PDGFR. Besides that, A 419259 is found to inhibit the production of IL-2 with IC50 value of 25nM in Jurkat cells. Moreover, administration of A 419259 reduces IL-2 production in mice with ED50 value of 2.5 mg/kg. A 419259 also has efficacy of the antigen specific T-Cell immune response. Administration of this compound inhibits IFN-γ production during the in vivo priming phase [1]
References:
[1] Calderwood D J, Johnston D N, Munschauer R, et al. Pyrrolo [2, 3-d] pyrimidines containing diverse N-7 substituents as potent inhibitors of Lck. Bioorganic & medicinal chemistry letters, 2002, 12(12): 1683-1686.
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An inhibitor-resistant mutant of Hck protects CML cells against the antiproliferative and apoptotic effects of the broad-spectrum Src family kinase inhibitor A-419259.[Pubmed:18794796]
Oncogene. 2008 Nov 27;27(56):7055-69.
Chronic myelogenous leukemia (CML) is driven by Bcr-Abl, a constitutively active protein-tyrosine kinase that stimulates proliferation and survival of myeloid progenitors. Global inhibition of myeloid Src family kinase (SFK) activity with the broad-spectrum pyrrolo-pyrimidine inhibitor, A-419259, blocks proliferation and induces apoptosis in CML cell lines, suggesting that transformation by Bcr-Abl requires SFK activity. However, the contribution of Hck and other individual SFKs to Bcr-Abl signaling is less clear. Here, we developed an A-419259-resistant mutant of Hck by replacing the gatekeeper residue (Thr-338; c-Src numbering) in the inhibitor-binding site with a bulkier methionine residue (Hck-T338M). This substitution reduced Hck sensitivity to A-419259 by more than 30-fold without significantly affecting kinase activity in vitro. Expression of Hck-T338M protected K-562 CML cells and Bcr-Abl-transformed TF-1 myeloid cells from the apoptotic and antiproliferative effects of A-419259. These effects correlated with persistence of Hck-T338M kinase activity in the presence of the compound, and were accompanied by sustained Erk and Stat5 activation. In contrast, control cells expressing equivalent levels of wild-type Hck retained sensitivity to the inhibitor. We also show for the first time that A-419259 induces cell-cycle arrest and apoptosis in primary CD34(+) CML cells with equal potency to imatinib. These data suggest that Hck has a nonredundant function as a key downstream signaling partner for Bcr-Abl and may represent a potential drug target in CML.