AG-1478(Tyrphostin AG-1478 NSC693255)

Molecular Weight (MW)	315.75
Formula	C16H14ClN3O2
CAS No.	153436-53-4
Storage	-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)	DMSO: 25 mg/mL (79.2 mM)
Water: <1 mg/mL
Ethanol: 13 mg/mL (41.2 mM)
Solubility (In vivo)	15% Captisol: 30mg/mL
Synonyms	Tyrphostin AG-1478; AG1478;Tyrphostin AG 1478; NSC 693255; NSC-693255; NSC693255; Chemical Name: N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine InChi Key: GFNNBHLJANVSQV-UHFFFAOYSA-N InChi Code: InChI=1S/C16H14ClN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20) SMILES Code: COC1=CC2=NC=NC(NC3=CC=CC(Cl)=C3)=C2C=C1OC

Molecular Weight (MW)

315.75

Formula

C16H14ClN3O2

CAS No.

153436-53-4

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 25 mg/mL (79.2 mM)

Water: <1 mg/mL

Ethanol: 13 mg/mL (41.2 mM)

Solubility (In vivo)

15% Captisol: 30mg/mL

Synonyms

Tyrphostin AG-1478; AG1478;Tyrphostin AG 1478; NSC 693255; NSC-693255; NSC693255;

Chemical Name: N-(3-chlorophenyl)-6,7-dimethoxyquinazolin-4-amine

InChi Key: GFNNBHLJANVSQV-UHFFFAOYSA-N

InChi Code: InChI=1S/C16H14ClN3O2/c1-21-14-7-12-13(8-15(14)22-2)18-9-19-16(12)20-11-5-3-4-10(17)6-11/h3-9H,1-2H3,(H,18,19,20)

SMILES Code: COC1=CC2=NC=NC(NC3=CC=CC(Cl)=C3)=C2C=C1OC

In Vitro	In vitro activity: AG-1478 (also known as Tyrphostin AG-1478) is a potent and selective EGFR (epidermal growth factor receptor) inhibitor with IC50 of 3 nM in cell-free assays. It reversibly inhibits rat brain Kv1.5 potassium channels with IC50 of 9.8 μM which is independent of protein tyrosine kinase (PTK) activity. AG-1478 also inhibits the growth of leiomyoma and myometrium cell cultures with IC50 values of 5.6 and 5.7 μM, respectively. Previous studies suggest that EGFR antagonism may be effective for the treatment of various diseases such as cancer, angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. Therefore, AG-1478 has the potential to be used as therapeutics for these disorders. Kinase Assay: AG-1478 is high selective over ErbB2 and PDGFR with IC50 of>100 μM. AG-1478 preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. AG-1478 also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. AG-1478 (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. AG-1478 inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. AG1478 is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2. Cell Assay: Cells are exposed to different concentrations of AG-1478 for 72 hours in 96-well plates. The effects of AG-1478 on cell growth are examined using an Alamar Blue assay. A 20-μL aliquot of Alamar Blue is added to each well, and its absorbance is determined using a Spectromax Scanning Micro plate Reader. The effects of AG-1478 are expressed as percentage of growth inhibition using untreated cells as the control (0% inhibition). Cellular DNA synthesis is determined using a [3H]thymidine incorporation assay.
In Vivo	Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of AG-1478 significantly enhance the efficacy of cytotoxic drugs, with the combination of AG-1478 and temozolomide displaying synergistic antitumor activity against human glioma xenografts. The combination of AG-1478 and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. The combination of AG-1478 (0.4 mg) with a single dose of 25 μCi 90Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone.
Animal model	Female BALB/c nu/nu mice inoculated s.c. with A431 or U87MG.Δ2-7 tumor cells
Formulation & Dosage	Dissolved in 100 mM Captisol; 1 mg/kg; i.p. injection
References	Cancer Res. 1996 Sep 1;56(17):3859-61; Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15871-6; Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7080s-7086s.

In Vitro

In vitro activity: AG-1478 (also known as Tyrphostin AG-1478) is a potent and selective EGFR (epidermal growth factor receptor) inhibitor with IC50 of 3 nM in cell-free assays. It reversibly inhibits rat brain Kv1.5 potassium channels with IC50 of 9.8 μM which is independent of protein tyrosine kinase (PTK) activity. AG-1478 also inhibits the growth of leiomyoma and myometrium cell cultures with IC50 values of 5.6 and 5.7 μM, respectively. Previous studies suggest that EGFR antagonism may be effective for the treatment of various diseases such as cancer, angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy. Therefore, AG-1478 has the potential to be used as therapeutics for these disorders.

Kinase Assay: AG-1478 is high selective over ErbB2 and PDGFR with IC50 of>100 μM. AG-1478 preferentially inhibits U87MG cells expressing truncated EGFR with IC50 of 8.7 μM, compared to those expressing endogenous wt EGFR or overexpressing exogenous wt EGFR with IC50 of 34.6 μM and 48.4 μM, respectively, and inhibits the DNA synthesis with IC50 of 4.6 μM, 19.67 μM, and 35.2 μM, respectively. AG-1478 also preferentially inhibits the tyrosine kinase activity and autophosphorylation of the ΔEGFR compared to endogenous or overexpressed exogenous wt EGFR. AG-1478 (0.25 μM) abolishes the MAPK activation induced by Ang II, a Ca2+ ionophore as well as EGF but not by a phorbol ester or platelet-derived growth factor-BB in the VSMC. AG-1478 inhibits EGF-induced mitogenesis of the BaF/ERX and LIM1215 cells with IC50 of 0.07 μM and 0.2 μM, respectively. AG1478 is able to inhibit the function of ATP-binding cassette (ABC) transporters such as ABCB1 and ABCG2, with a more pronounced effect on ABCG2.

Cell Assay: Cells are exposed to different concentrations of AG-1478 for 72 hours in 96-well plates. The effects of AG-1478 on cell growth are examined using an Alamar Blue assay. A 20-μL aliquot of Alamar Blue is added to each well, and its absorbance is determined using a Spectromax Scanning Micro plate Reader. The effects of AG-1478 are expressed as percentage of growth inhibition using untreated cells as the control (0% inhibition). Cellular DNA synthesis is determined using a [3H]thymidine incorporation assay.

In Vivo

Administration of AG-1478 blocks phosphorylation of the EGFR at the tumor site and inhibits the growth of A431 xenografts that overexpress the WT EGFR and glioma xenografts expressing the de2-7 EGFR. Even subtherapeutic doses of AG-1478 significantly enhance the efficacy of cytotoxic drugs, with the combination of AG-1478 and temozolomide displaying synergistic antitumor activity against human glioma xenografts. The combination of AG-1478 and an anti-EGFR antibody (mAb 806) displays additive and in some cases synergistic, antitumor activity against tumor xenografts overexpressing the EGFR. The combination of AG-1478 (0.4 mg) with a single dose of 25 μCi 90Y-CHX-A''-DTPA-hu3S193 results in a significant enhancement of efficacy compared with either agent alone.

Animal model

Female BALB/c nu/nu mice inoculated s.c. with A431 or U87MG.Δ2-7 tumor cells

Formulation & Dosage

Dissolved in 100 mM Captisol; 1 mg/kg; i.p. injection

References

Cancer Res. 1996 Sep 1;56(17):3859-61; Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15871-6; Clin Cancer Res. 2005 Oct 1;11(19 Pt 2):7080s-7086s.

CAS NO:	153436-53-4
规格:	≥98%

包装	价格(元)
25mg	电议
50mg	电议
100mg	电议
250mg	电议
500mg	电议
1g	电议