| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Tyrphostin AG 957 targets the Abl tyrosine kinase and the Bcr-Abl fusion protein. It acts as a competitive inhibitor of ATP binding to the kinase active site. By inhibiting Abl and Bcr-Abl, tyrphostin AG 957 blocks the downstream signaling pathways that promote cell proliferation and survival. The compound has been shown to be effective against imatinib-resistant Bcr-Abl mutants in some studies.
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| ln Vitro |
AG957 attenuates tyrosine kinase activity of p210bcr-abl. DNA synthesis is 40% inhibited at 20 microM by AG957 as early as 2 hours. While total protein phosphorylation is not inhibited, AG957 reduces the tyrosine phosphorylation of p210BCR/ABL in living cells by 1 hour[1]. Beta1 integrin function in CML progenitors is affected by Tyrphostin AG957, a protein tyrosine kinase (PTK) inhibitor that exhibits activity against the p210BCR/ABL kinase[2].
AG957 (0.1-100 μM ) pretreatment significantly reduces the proliferation of colony-forming cells (CFC) associated with chronic myelogenous leukemia (CML)[2]. AG957 (25 μM) partially inhibits the phosphorylation of multiple proteins that are substrates of BCR/ABL PTK and involved in normal integrin signaling in BCR/ABL expressing cells[2]. In vitro, Tyrphostin AG 957 has been shown to potently inhibit the kinase activity of Abl and Bcr-Abl. It inhibits the proliferation of Bcr-Abl-positive cell lines, such as K562 cells, in a concentration-dependent manner. The compound induces apoptosis in these cells. Tyrphostin AG 957 has also been shown to inhibit the phosphorylation of downstream signaling proteins, including STAT5 and CrkL. |
| ln Vivo |
AG957 (10 mg/kg; intratracheally administered 1 h prior to intratracheal LPS challenge) inhibits c-Abl activity in the lung of mice[4].
In vivo, Tyrphostin AG 957 has been studied in animal models of CML. The compound has been shown to reduce tumor burden and prolong survival in mice engrafted with Bcr-Abl-positive cells. Tyrphostin AG 957 is typically administered orally or intraperitoneally. The compound's efficacy in vivo is associated with the inhibition of Bcr-Abl kinase activity and the induction of apoptosis in leukemia cells. |
| Enzyme Assay |
In vitro kinase assays for Tyrphostin AG 957 typically involve measuring the activity of recombinant Abl or Bcr-Abl kinase in the presence of varying concentrations of the compound. The kinase is incubated with a peptide substrate and ATP, and the incorporation of phosphate into the substrate is measured. The IC50 value for inhibition of the kinase is determined from dose-response curves. The selectivity of Tyrphostin AG 957 for Abl over other kinases can be assessed.
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| Cell Assay |
Cell Line: CML and CFC
Concentration: 0, 0.1, 1, 10, 100 μM Incubation Time: Pretreatment for 1 hour Result: A significant dose-dependent inhibition of CML CFC growth was seen following preincubation with AG957. In vitro cell-based studies with Tyrphostin AG 957 typically involve cultured Bcr-Abl-positive cell lines, such as K562 cells. Cells are treated with Tyrphostin AG 957 at various concentrations for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is evaluated by Annexin V/PI staining or by detecting caspase activity. The effect of Tyrphostin AG 957 on Bcr-Abl signaling is examined by Western blot analysis of phospho-STAT5, phospho-CrkL, and other downstream targets. |
| Animal Protocol |
C57BL/6J mice
10 mg/kg Intratracheally 1 h before intratracheal LPS challenge In vivo animal studies with Tyrphostin AG 957 are typically conducted in xenograft or syngeneic mouse models of CML. Mice are engrafted with Bcr-Abl-positive cells and then treated with Tyrphostin AG 957 via oral or intraperitoneal administration. Tumor burden is assessed by measuring spleen size, white blood cell count, and leukemic cell infiltration in tissues. Survival is monitored. Pharmacokinetic studies are performed to evaluate the absorption and distribution of the compound. |
| ADME/Pharmacokinetics |
The pharmacokinetic properties of Tyrphostin AG 957 have been studied in preclinical settings. Following oral administration, the compound is absorbed from the gastrointestinal tract. Tyrphostin AG 957 is metabolized in the liver. The elimination half-life is relatively short. Detailed PK parameters such as Cmax, Tmax, AUC, and half-life have been reported in the literature.
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| Toxicity/Toxicokinetics |
The toxicity profile of Tyrphostin AG 957 has been evaluated in preclinical studies. The compound has been shown to have a relatively low toxicity in animal models at therapeutic doses. However, higher doses can cause adverse effects, including gastrointestinal upset and hepatotoxicity. The compound is for research use only and is not approved for human therapeutic use.
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| References |
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| Additional Infomation |
4-[(2,5-dihydroxyphenyl)methylamino]benzoate is an aromatic amine. Tyrosine kinase inhibitor AG 957 belongs to the tyrosine kinase inhibitor family and selectively inhibits the activity of human p210 tyrosine kinase. (NCI)
Tyrphostin AG 957 is a research compound with potent inhibitory activity against the Abl tyrosine kinase and the Bcr-Abl fusion protein. It is used as a research tool to study tyrosine kinase signaling and its role in cancer. Tyrphostin AG 957 has been investigated for its potential therapeutic applications in chronic myeloid leukemia. The compound is not an FDA-approved drug and is not commercially available as a pharmaceutical product. |
| Molecular Formula |
C15H15NO4
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|---|---|
| Molecular Weight |
273.2839
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| Exact Mass |
273.1
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| Elemental Analysis |
C, 65.92; H, 5.53; N, 5.13; O, 23.42
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| CAS # |
140674-76-6
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| Related CAS # |
Solid powder
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| PubChem CID |
2064
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| Appearance |
Off-white to light brown solid powder
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| LogP |
2.569
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
20
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| Complexity |
315
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O([H])C1C([H])=C([H])C(=C([H])C=1C([H])([H])N([H])C1C([H])=C([H])C(C(=O)OC([H])([H])[H])=C([H])C=1[H])O[H]
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| InChi Key |
QSFREBZMBNRGOK-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H15NO4/c1-20-15(19)10-2-4-12(5-3-10)16-9-11-8-13(17)6-7-14(11)18/h2-8,16-18H,9H2,1H3
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| Chemical Name |
methyl 4-[(2,5-dihydroxyphenyl)methylamino]benzoate
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| Synonyms |
AG-957; AG 957; AG957; Tyrphostin AG957; Tyrphostin-AG957; TyrphostinAG957; Tyrphostin AG-957; Tyrphostin AG 957
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| HS Tariff Code |
2934.99.03.00
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| 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)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.6593 mL | 18.2963 mL | 36.5925 mL | |
| 5 mM | 0.7319 mL | 3.6593 mL | 7.3185 mL | |
| 10 mM | 0.3659 mL | 1.8296 mL | 3.6593 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.
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