Tyrphostin AG17
Tyrphostin AG17 is an orally active CDK2 inhibitor and EGFR tyrosine kinase antagonist. Tyrphostin AG17 reduces the levels of p21 and p16. Tyrphostin AG17 induces G1 phase cell cycle arrest, Apoptosis, mitochondrial dysfunction, decreased ATP levels, and inhibits DNA, RNA and protein synthesis, adipogenesis, and lipid synthesis. Tyrphostin AG17 inhibits fat accumulation, white adipose tissue hypertrophy, and alterations of glycogen and lipid inclusions in hepatocytes in obese mice without changing their serum biochemical parameters. Tyrphostin AG17 exhibits anticancer effects. Tyrphostin AG17 can be used in research related to immunoblastic lymphoma, leukemia, ovarian cancer, glioblastoma, colon cancer, breast cancer, melanoma, obesity and hepatic steatosis.
For research use only. We do not sell to patients.
- CAS No.: 71308-35-5
- Formula: C12H10N2O
- Molecular Weight:198.22
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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CDK2 |
Tyrphostin AG17 (0.5-50 μM; 24 h) potently inhibits DNA synthesis in OCI-Ly8 immunoblastic lymphoma cells, with nearly complete inhibition observed at a concentration of 5 μM, and exhibits the strongest efficacy among the 16 tested tyrosine phosphorylation inhibitors[1].
Tyrphostin AG17 does not alter the intracellular ATP level of OCI-Ly8 immunoblastic lymphoma cells[1].
Tyrphostin AG17 reduces global protein tyrosine phosphorylation in a reversible or irreversible manner depending on the exposure mode, and decreases p21 and p16 protein levels in OCI-Ly8 immunoblastic lymphoma cells without altering Bcl-2 or cdk2 protein levels[1].
Tyrphostin AG17 potently reduces cdk2 kinase activity in OCI-Ly8 immunoblastic lymphoma cells without altering cdk2 protein levels[1].
Tyrphostin AG17 (6 days) inhibits the growth of tumor cell lines, with a GI50 value ranging from 0.7 to 4.0 μM after 6 days of continuous treatment. Among these cell lines, HL-60 (TB) cells are the most sensitive (GI50 = 0.7 μM, TGI = 1.5 μM)[2].
Tyrphostin AG17 (2 μM; 2-24 h) rapidly reduces intracellular ATP levels in HL-60 (TB) cells, decreasing ATP levels by 50% within 2 h of exposure and by 85% within 24 h of exposure[2].
Tyrphostin AG17 (1 μM) potently inhibits the differentiation and lipid accumulation of 3T3-L1 preadipocytes[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:OCI-Ly8 immunoblastic lymphoma cells
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Concentration:0.5 μM (daily treatment for 5 consecutive days); 1 μM (single treatment); 5 μM (single treatment, two treatments with the second dose administered 3 days after the first)
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Incubation Time:single treatment (assessed over up to 9 days); two treatments (assessed over unspecified time); daily treatment for 5 consecutive days (assessed over unspecified time)
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Result:Did not cause significant cell death with a single 1 μM dose.
Arrested cell growth for 7 days with a single 5 μM dose, with growth recovery starting on day 9.
Resulted in cell death with two 5 μM doses (with the second given 3 days after the first).
Caused cells to grow slightly slower than controls for the first 3 days, followed by rapid cell death with daily 0.5 μM doses for 5 consecutive days.
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Cell Line:OCI-Ly8 immunoblastic lymphoma cells
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Concentration:0.5 μM (daily treatment for 5 consecutive days); 5 μM (single treatment, two treatments)
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Incubation Time:single 5 μM dose (analyzed at 1, 3, 10, 12 days); two treatments (analyzed at unspecified time); daily 0.5 μM doses for 5 days (analyzed at unspecified time)
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Result:Reduced global protein tyrosine phosphorylation with a single 5 μM dose, with a detectable effect at 1 day, dramatic reduction at 3 days, and full recovery by 12 days.
Caused permanent tyrosine dephosphorylation concurrent with apoptosis with multiple exposures.
Had no effect on Bcl-2 or cdk2 protein levels.
Caused marked reductions in p21 and p16 protein levels following both dual 5 μM doses and daily 0.5 μM doses for 5 days.
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Cell Line:HL-60(TB), K-562, Molt-4, SR, Ovcar-3, SNB-19, Colo 205, HCT-116, HS 578T, MCF-7, SK-MEL-5, A498, HOP-92
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Concentration:Unclear
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Incubation Time:6 days
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Result:Inhibited growth across all 13 cell lines, with GI50 values ranging from 0.7 μM (HL-60(TB)) to 4.0 μM (MCF-7).
Exhibited TGI values ranging from 1.5 μM (HL-60(TB)) to 39.0 μM (SNB-19).
Showed steep concentration-effect curves for most cell lines, with GI50 and TGI values spanning 1-6 μM, except for SNB-19, MCF-7, and A498 which had significantly higher TGI values (P < 0.05).
Tyrphostin AG17 (1.75-55.5 mg/kg; p.o.; single dose) has an LD50 of 33.3 mg/kg in C57BL/6 mice, with transient behavioral effects at doses ≤17.5 mg/kg, 60% mortality at 40 mg/kg, 100% mortality at 28 mg/kg and 55.5 mg/kg, morphological changes in brain, kidney, liver, pancreas, and WAT at doses ≥17.5 mg/kg, and no changes in key serum biochemical markers in survivors, while skeletal muscle remains unaltered[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (2 month-old male; diet-induced obesity via 18-week high-fat diet feeding)[3]
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Dosage:0.175 mg/kg
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Administration:p.o.; daily; 2 weeks
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Result:Decreased white adipose tissue (WAT) adipocyte fat droplet size.
Induced a significant increase in active pro-caspase 3 staining in WAT, indicating adipocyte apoptosis.
Promoted a switch from macrovesicular to microvesicular steatosis in hepatocytes, which correlated with an increase in oil red-positive lipid inclusions, and increased glycogen accumulation as shown by PAS staining.
Caused no significant body weight loss.
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Animal Model:C57BL/6 (2 month-old male)[3]
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Dosage:1.75 mg/kg; 5.5 mg/kg; 17.5 mg/kg; 28 mg/kg; 40 mg/kg; 55.5 mg/kg
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Administration:p.o.; single dose
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Result:Caused 100% mortality within 15 minutes at 55.5 mg/kg.
Caused 60% mortality after 2 days at 40 mg/kg.
Caused 100% mortality after 7 days at 28 mg/kg.
Calculated LD50 as 33.3 mg/kg.
Induced transient locomotion inhibition and piloerection lasting up to 30 minutes but no mortality at 1.75, 5.5, and 17.5 mg/kg.
Caused no altered serum levels of glucose, insulin, or leptin in survivors from all acute doses.
Induced morphological changes in brain, kidney, liver, pancreas, and WAT at doses ≥17.5 mg/kg, including perinuclear vacuoles in hepatocytes, pale glomerular units and proximal tubules in kidneys, pale exocrine acinar cells in pancreas, and reduced adipocyte number in WAT.
Caused no morphological alteration in skeletal muscle.
Chemical Information
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CAS No. 71308-35-5
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Molecular Weight 198.22
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Formula C12H10N2O
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SMILES
N#C/C(C#N)=C/C1=CC(C)=C(O)C(C)=C1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
[1]. Palumbo GA, et al. The tryphostin AG17 induces apoptosis and inhibition of cdk2 activity in a lymphoma cell line that overexpresses bcl-2. Cancer research. 1997 Jun 15;57(12):2434-9. [Content Brief]
[2]. Burger AM, et al. Tyrphostin AG17, [(3,5-Di-tert-butyl-4-hydroxybenzylidene)- malononitrile], inhibits cell growth by disrupting mitochondria. Cancer research. 1995 Jul 01;55(13):2794-9. [Content Brief]
[3]. Camacho A, et al. Tyrphostin AG17 inhibits adipocyte differentiation in vivo and in vitro. Lipids in health and disease. 2018 May 29;17(1):128. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Tyrphostin AG17 Related Classifications
HY-183456 Related Classifications
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- Tyrphostin AG17
- 71308-35-5
- Tyrphostin AG 17
- Tyrphostin AG-17
- CDK
- EGFR
- Apoptosis
- Mitochondrial Metabolism
- ATP Synthase
- DNA/RNA Synthesis
- CDK2
- OCI-Ly8 immunoblastic lymphoma cells
- 3T3-L1 preadipocytes
- p16
- EGFR tyrosine kinase
- p21
- cell cycle arrest
- C57BL/6 mice
- apoptosis
- HL-60 human myeloblastic leukemia cells
- Inhibitor
- inhibitor
- inhibit