product name AMG-458
Description: AMG 208 is a highly potent and selective c-Met inhibitor with IC50 of 9 nM. Recent study investigated the effect of AMG-456 treatment on cell radiosensitizing response. The results showed that AMG-458 treatment enhanced radiosensitivity in H441 with higher levels of c-Met but not in A549 with lower expression of c-Met. AMG-458 was found to significantly inhibit tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.
References: J Med Chem. 2008 Jul 10;51(13):3688-91; Chem Res Toxicol. 2008 Nov;21(11):2216-22.
539.58
Formula
C30H29N5O5
CAS No.
913376-83-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 21 mg/mL (38.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol+citrate vehicle: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402777
| In Vitro |
In vitro activity: AMG 458 also inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM. AMG 458 is observed to bind covalently to liver microsomal proteins from rats and humans in the absence of NADPH. AMG 458 is believed to react with thiol groups in proteins, producing a methoxy quinoline thioether conjugate. A recent study shows that the constitutive phosphorylation of c-Met in H441 is abrogated by AMG 458. The basal and HGF-induced phosphorylation of c-Met in A549 is attenuated by AMG 458. The combination of radiation therapy and AMG 458 treatment is found to synergistically increase apoptosis in the H441 cell line by reduction of p-Akt and p-Erk levels, but not in A549. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | AMG 458 is metabolically stable in the liver microsomes of mouse, rat, dog, monkey, and human with low intrinsic clearances (Clint: <5, 62, 8, 8, 18 (μL/min)/mg, respectively). When administered orally, AMG 458 achieves remarkably high bioavailability in all species tested. Oral dosing of AMG 458 inhibits HGF-mediated c-Met phosphorylation with an approximate ED90 of 30 mg/kg and an associated plasma exposure of approximately 15 μM at 6 hours. AMG 458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d.with no adverse effect on body weight. High concentrations of AMG 458 in some organs may produce toxicity via oxidative stress. |
| Animal model | Female CD-1 nu/nu mice aged 6-8) bearing NIH3T3/TPR-Met and U-87 MG xenograft model |
| Formulation & Dosage | Formulated in 20% Captisol with pH adjusted to 3.5 using methanesulfonic acid (i.v. injection); Formulated in 2% HPMC and 1% Tween-80 with pH adjusted to 2.2 using HCl (p.o.); 10, 30, 100 mg/kg; i.v. or p.o. |
| References | J Med Chem. 2008 Jul 10;51(13):3688-91; Chem Res Toxicol. 2008 Nov;21(11):2216-22. |
Related Posts
product name AMG-458
Description: AMG 208 is a highly potent and selective c-Met inhibitor with IC50 of 9 nM. Recent study investigated the effect of AMG-456 treatment on cell radiosensitizing response. The results showed that AMG-458 treatment enhanced radiosensitivity in H441 with higher levels of c-Met but not in A549 with lower expression of c-Met. AMG-458 was found to significantly inhibit tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models with no adverse effect on body weight.
References: J Med Chem. 2008 Jul 10;51(13):3688-91; Chem Res Toxicol. 2008 Nov;21(11):2216-22.
539.58
Formula
C30H29N5O5
CAS No.
913376-83-7
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 21 mg/mL (38.9 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
15% Captisol+citrate vehicle: 30 mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19402777
| In Vitro |
In vitro activity: AMG 458 also inhibits HGF-mediated c-Met phosphorylation in PC3 and CT26 cells with IC50 of 60 and 120 nM. AMG 458 is observed to bind covalently to liver microsomal proteins from rats and humans in the absence of NADPH. AMG 458 is believed to react with thiol groups in proteins, producing a methoxy quinoline thioether conjugate. A recent study shows that the constitutive phosphorylation of c-Met in H441 is abrogated by AMG 458. The basal and HGF-induced phosphorylation of c-Met in A549 is attenuated by AMG 458. The combination of radiation therapy and AMG 458 treatment is found to synergistically increase apoptosis in the H441 cell line by reduction of p-Akt and p-Erk levels, but not in A549. Kinase Assay: Cell Assay: |
|---|---|
| In Vivo | AMG 458 is metabolically stable in the liver microsomes of mouse, rat, dog, monkey, and human with low intrinsic clearances (Clint: <5, 62, 8, 8, 18 (μL/min)/mg, respectively). When administered orally, AMG 458 achieves remarkably high bioavailability in all species tested. Oral dosing of AMG 458 inhibits HGF-mediated c-Met phosphorylation with an approximate ED90 of 30 mg/kg and an associated plasma exposure of approximately 15 μM at 6 hours. AMG 458 significantly inhibits tumor growth in the NIH3T3/TPR-Met and U-87 MG xenograft models at 30 and 100 mg/kg q.d. and 30 mg/kg b.i.d.with no adverse effect on body weight. High concentrations of AMG 458 in some organs may produce toxicity via oxidative stress. |
| Animal model | Female CD-1 nu/nu mice aged 6-8) bearing NIH3T3/TPR-Met and U-87 MG xenograft model |
| Formulation & Dosage | Formulated in 20% Captisol with pH adjusted to 3.5 using methanesulfonic acid (i.v. injection); Formulated in 2% HPMC and 1% Tween-80 with pH adjusted to 2.2 using HCl (p.o.); 10, 30, 100 mg/kg; i.v. or p.o. |
| References | J Med Chem. 2008 Jul 10;51(13):3688-91; Chem Res Toxicol. 2008 Nov;21(11):2216-22. |