| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
A-419259 targets Src family kinases (SFKs), a group of non-receptor tyrosine kinases that play critical roles in cell proliferation, survival, migration, and differentiation. SFKs include Src, Lck, Lyn, Fyn, Yes, and other members. A-419259 is a broad-spectrum pyrrole-pyrimidine inhibitor designed to enhance selectivity for the Src family. It targets Src, Lck, and Lyn with IC50 values of 9 nM, <3 nM, and <3 nM, respectively. It also inhibits other Src family members such as Fyn, Blk, and Csk. By inhibiting SFKs, A-419259 blocks downstream signaling pathways, including Stat5 and Erk activation, leading to cell cycle arrest and apoptosis in cancer cells.
|
|---|---|
| ln Vitro |
In comparison to other cytoplasmic tyrosine kinases, 419259 is a second-generation pyrrolopyrimidine that is intended to improve selectivity for the Src family. K-562 cells are inhibited by A-419259 with an IC50 of 0.1–0.3 μM, while Meg-01 proliferation is inhibited with an IC50 of about 0.1 μM. Moreover, A-419259 potently triggered apoptosis in K-562 cells, with dose-dependent increases beginning at 0.1 μM. In two Ph+ cell lines (K-562 and Meg-01), PP2 inhibits Src kinase autophosphorylation with an IC50 ranging from 3 to 10 μM, while A-419259 blocks kinase activation with an IC50 ranging from 0.1 to 0.3 μM. With an IC50 ranging from 0.1 to 0.3 μM, A-419259 significantly suppresses the proliferation of DAGM/Bcr-Abl cells in the absence of IL-3 [1]. A-419259 is a broad-spectrum pyrrolopyrimidine inhibitor that causes CML cell lines to undergo apoptosis and stops proliferation. In K562 and other CML cell lines, A-419259 inhibits total SFK activity with IC50 values ranging from 0.1 to 0.3 μM [2].
In vitro studies have demonstrated that A-419259 is a potent inhibitor of Src family kinases. It targets Src, Lck, and Lyn with IC50 values of 9 nM, <3 nM, and <3 nM, respectively. It also inhibits Fyn, Blk, Csk, and other Src family members. In cell-based assays, A-419259 inhibits the proliferation of K-562 cells with an IC50 of 0.1–0.3 µM and Meg-01 cells with an IC50 of approximately 0.1 µM. It potently triggers apoptosis in K-562 cells in a dose-dependent manner, with effects beginning at 0.1 µM. A-419259 blocks Src kinase autophosphorylation with an IC50 of 0.1–0.3 µM, which is more potent than PP2 (IC50 of 3–10 µM). It significantly suppresses the proliferation of DAGM/Bcr-Abl cells in the absence of IL-3 with an IC50 of 0.1–0.3 µM. A-419259 inhibits total SFK activity in K562 and other CML cell lines with IC50 values of 0.1–0.3 µM. These findings confirm that A-419259 is a potent inhibitor of Src family kinases with anti-proliferative and pro-apoptotic effects in CML cells. |
| ln Vivo |
In vivo activity data for A-419259 is limited, as the compound is primarily used as a research tool in in vitro studies. However, its mechanism of action—inhibiting Src family kinases and inducing apoptosis in CML cell lines—suggests potential in vivo applications in studying hematological malignancies. The compound's ability to inhibit SFK activity and induce apoptosis in CML cells makes it a valuable tool for studying the role of SFKs in cancer. However, specific in vivo protocols and results, such as dosing regimens, routes of administration, and pharmacokinetic parameters, are not detailed in the available literature.
|
| Enzyme Assay |
The in vitro kinase assays for A-419259 measure its inhibition of Src family kinases. In a typical assay, recombinant Src family kinases (e.g., Src, Lck, Lyn) are incubated with a peptide substrate and ATP in the presence of varying concentrations of A-419259. The incorporation of phosphate into the substrate is measured using a radiometric or fluorescent method. The inhibition of kinase activity is calculated, and the IC50 is determined from the dose-response curve. For A-419259, the IC50 values for Src, Lck, and Lyn are 9 nM, <3 nM, and <3 nM, respectively. To confirm selectivity, the compound is tested against a panel of other kinases. These assays provide a quantitative measure of A-419259's potency and selectivity at the molecular level.
|
| Cell Assay |
In vitro cell-based assays for A-419259 are used to study its effects on Src family kinase signaling and cancer cell biology. A common assay involves treating CML cell lines (e.g., K-562, Meg-01) with varying concentrations of A-419259. Cell proliferation is assessed using assays such as MTT or CellTiter-Glo, and the IC50 for growth inhibition is determined. Apoptosis is measured using Annexin V staining or caspase-3/7 activation assays. The phosphorylation of SFKs and downstream signaling molecules, such as Stat5 and Erk, is assessed by Western blotting. These cell-based assays confirm that A-419259 inhibits SFK activity and exerts anti-proliferative and pro-apoptotic effects in cancer cells.
|
| Animal Protocol |
In vivo animal experiments for A-419259 are not extensively described in the available literature. As a research compound, its use in vivo would be determined by the specific research question being addressed. A typical protocol for studying an SFK inhibitor like A-419259 would involve its administration to animal models of cancer, such as xenograft models of CML or other hematological malignancies. The compound would be formulated for injection, likely using a vehicle that includes DMSO, PEG, and saline. It could be administered via intraperitoneal (i.p.) or intravenous (i.v.) injection at a predetermined dose and schedule. Endpoints would include assessment of tumor growth, SFK phosphorylation, and apoptosis markers. However, specific protocols for A-419259 are not detailed in the available literature.
|
| ADME/Pharmacokinetics |
A-419259 has a molecular weight of 482.62 g/mol and a molecular formula of C29H34N6O. It has a logP of 8.066. The compound is supplied as an off-white to light yellow solid powder. It is soluble in DMSO and other organic solvents. For storage, it is recommended to keep the powder at -20°C. The compound is stable under recommended storage conditions. Pharmacokinetic properties such as absorption, distribution, metabolism, and excretion (ADME) have not been extensively characterized. A-419259 is a research compound and is not intended for human or veterinary use.
|
| Toxicity/Toxicokinetics |
Detailed toxicity data for A-419259 is not provided in standard product descriptions. As a research compound, its toxicity profile has not been extensively characterized. A-419259 is a potent inhibitor of Src family kinases, and its toxicity would be related to its effects on SFK-mediated signaling pathways in normal tissues. As with all research chemicals, standard laboratory safety precautions should be followed when handling A-419259. Its use is limited to research applications and it is not intended for human or veterinary use.
|
| References |
[1]. Wilson MB, et al. Selective pyrrolo-pyrimidine inhibitors reveal a necessary role for Src family kinases in Bcr-Abl signal transduction and oncogenesis. Oncogene. 2002 Nov 21;21(53):8075-88.
[2]. Pene-Dumitrescu T, et al. 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.Oncogene (2008) 27, 7055-7069 [3]. Anthony Cheung, et al. Anti-Folate Receptor Alpha-Directed Antibody Therapies Restrict the Growth of Triple-negative Breast Cancer. Clin Cancer Res. 2018 Oct 15;24(20):5098-5111 |
| Additional Infomation |
A-419259 (RK-20449) is a research compound and is not approved for any clinical or therapeutic use. It is a broad-spectrum pyrrole-pyrimidine inhibitor with enhanced selectivity for the Src family of kinases. A-419259 targets Src, Lck, and Lyn with IC50 values of 9 nM, <3 nM, and <3 nM, respectively. It is a potent inhibitor of Src family kinases, with IC50 values for src, lck, blk, csk, fyn, and lyn ranging between 15 and 50 nM. A-419259 causes CML cell lines to undergo apoptosis and stops proliferation. It inhibits SFK activity and blocks Stat5 and Erk activation. A-419259 is used to study Src family kinase signaling in cancer and other diseases. Its mechanism of action involves inhibiting SFK activity, leading to cell cycle arrest and apoptosis in cancer cells.
|
| Molecular Formula |
C29H34N6O
|
|---|---|
| Molecular Weight |
482.62
|
| Exact Mass |
482.279
|
| CAS # |
364042-47-7
|
| Related CAS # |
A 419259 trihydrochloride;1435934-25-0
|
| PubChem CID |
6539952
|
| Appearance |
Off-white to light yellow solid powder
|
| LogP |
8.066
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
36
|
| Complexity |
679
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1CCN(CC1)C2CCC(CC2)N3C=C(C4=C(N=CN=C43)N)C5=CC=C(C=C5)OC6=CC=CC=C6
|
| InChi Key |
FDVSOQRNTAPCHB-UHFFFAOYSA-N
|
| InChi Code |
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)
|
| Chemical Name |
7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine
|
| Synonyms |
A419259 A 419259A-419259 trihydrochloride RK-20449 RK 20449RK20449
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~207.20 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.18 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0720 mL | 10.3601 mL | 20.7202 mL | |
| 5 mM | 0.4144 mL | 2.0720 mL | 4.1440 mL | |
| 10 mM | 0.2072 mL | 1.0360 mL | 2.0720 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
