STA-1474
STA-1474 is an orally active and highly selective HSP90 inhibitor, as well as a phosphate prodrug of the HSP90 inhibitor STA-9090 (HY-15205). STA-1474 disrupts the chaperone function of HSP90 and promotes the degradation of client proteins. STA-1474 inhibits the phosphorylation of Met, Akt and STAT3, thereby blocking related signaling pathways. STA-1474 induces apoptosis and inhibits proliferation of osteosarcoma cells, and triggers the up-regulation of HSP70 and HSP90. STA-1474 induces tumor regression and caspase-3 activation in mouse osteosarcoma xenograft models. STA-1474 can be used in the research of osteosarcoma.
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- No. CAS: 1118915-78-8
- Fòrmula: C20H21N4O6P
- Peso molecular:444.38
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Actividad biológica
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HSP90 |
HSP70 |
Caspase 3 |
p-STAT3 |
Met |
Akt |
STA-1474 (0.001-1 μM; 1-7 days) potently inhibits the proliferation of D17, OSA2, OSA8 and MG63 osteosarcoma cell lines, with IC50 values ranging from 0.011 μM to 0.043 μM, and exhibits selectivity for OSA cells relative to normal canine osteoblasts (IC50 = 0.072 μM)[1].
STA-1474 (0.1 μM; 24-48 h, followed by drug-free incubation for 2-6 h) mediates time-dependent and reversible downregulation of p-STAT3 in MG63 and D17 osteosarcoma cell lines, which confirms that this effect directly results from HSP90 inhibition rather than non-specific toxicity[1].
STA-1474 (0.01-1 μM; 24-48 h) induces dose-dependent apoptosis in OSA8 and MG63 osteosarcoma cell lines, but does not affect apoptosis in normal canine osteoblasts; it activates caspase 3/7 in a dose-dependent manner in D17 and OSA8 osteosarcoma cell lines, and induces dose-dependent PARP cleavage in D17, OSA2, OSA8 and MG63 osteosarcoma cell lines; it downregulates HSP90 client proteins (p-Met, total Met, p-Akt, total Akt, p-STAT3), and induces upregulation of stress response proteins HSP70 and HSP90[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:canine osteosarcoma (OSA) cell lines D17, OSA2, OSA8, human OSA cell line MG63, normal canine osteoblasts
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Concentration:0.001, 0.01, 0.1, 1 μM (proliferation analysis)
0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1 μM (IC50 assay) -
Incubation Time:1, 3, 5, 7 days (proliferation analysis)
5 days (IC50 assay) -
Result:Inhibited the growth of all tested OSA cell lines in a dose- and time-dependent manner, with variable sensitivity among cell lines.
Exhibited IC50 values of 0.011 μM in OSA8 cells, 0.043 μM in MG63 cells, and 0.072 μM in normal canine osteoblasts.
Inhibited proliferation of D17 and OSA2 cell lines at lower concentrations than those required to inhibit normal canine osteoblasts.
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Cell Line:canine OSA cell line OSA8, human OSA cell line MG63, normal canine osteoblasts
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Concentration:0.01, 0.1, 1 μM
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Incubation Time:48 h
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Result:Induced apoptosis in OSA8 and MG63 cells in a dose-dependent manner.
Caused no significant increase in apoptosis in normal canine osteoblasts across all tested concentrations.
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Cell Line:canine OSA cell lines D17, OSA2, OSA8, human OSA cell line MG63
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Concentration:0.01, 0.1, 1 μM
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Incubation Time:48 h
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Result:Induced dose-dependent cleavage of PARP in D17, OSA2, OSA8, and MG63 cells, with increasing levels of cleaved PARP detected at 0.1 μM and 1 μM concentrations.\nDownregulated rhHGF-induced p-Met and total Met expression at 0.1 μM in all OSA cell lines.
Caused dose-dependent downregulation of p-Akt and total Akt, and downregulation of p-STAT3.
Induced dose-dependent upregulation of HSP70 and HSP90 at 0.1 μM and 1 μM, consistent with a stress response to HSP90 inhibition.
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Cell Line:human OSA cell line MG63, canine OSA cell line D17
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Concentration:0.1 μM
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Incubation Time:24 h, 48 h; 24/48 h followed by drug-free incubation for 2 h, 4 h, 6 h
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Result:Caused time-dependent downregulation of p-STAT3 in MG63 and D17 cells, with levels decreasing after 24 hours and further after 48 hours.
Restored p-STAT3 levels rapidly within 6 hours following removal of STA-1474, while total STAT3 levels remained unchanged throughout treatment and drug withdrawal.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C.B-17 SCID (female, 7-8-week-old)[1]
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Dosage:60 mg/kg
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Administration:i.v.; 3 times per week; 2 weeks (tumor growth/regression)
i.v.; single dose (biomarker/apoptosis studies) -
Result:Achieved a %T/C value of 26 at study end.
Induced regression in 57% of tumors.
Significantly increased the average number of cleaved caspase-3 positive cells in tumors compared to vehicle controls.
Decreased tumor levels of p-Met, total Met, p-Akt, and total Akt relative to vehicle controls.
Increased HSP70 expression relative to vehicle controls.
Resulted in a 20.2% average bodyweight change relative to study start on day 83.
Chemical Information
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No. CAS 1118915-78-8
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Peso molecular 444.38
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Fòrmula C20H21N4O6P
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SMILES
O=C1NN=C(C2=CC(C(C)C)=C(OP(O)(O)=O)C=C2O)N1C3=CC4=C(N(C)C=C4)C=C3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
STA-1474 Related Classifications
HY-13752 Related Classifications
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