NPS-1034 is a dual inhibitor of Axl and MET with IC50 values of 10.3 and 48 nM, respectively. NPS-1034 inhibits the viability of the MKN45 and SNU638 cell lines, which highly express the MET gene and p-MET (phosphorylated MET), with IC50 values of 112.7 and 190.3 nmol, respectively. NPS-1034 also inhibits hepatocyte growth factor (HGF)-stimulated MET autophosphorylation (Y1234/1235) in the AGS and MKN1 cell lines with IC50 values of <10 and <50 nmol, respectively.
In vivo, NPS-1034 (10 mg/kg, p.o.) decreases tumor growth in SCID mice bearing HCC827/GR tumor xenografts. In nude mice bearing MKN45 xenograft tumors, NPS-1034 (30 mg/kg, p.o.) decreases tumor growth through the inhibition of angiogenesis and the promotion of apoptosis.
| Cell Experiment | |
|---|---|
| Cell lines | HCC827/GR, HCC-78 and H820 cells |
| Preparation method | To perform the MTT assay, cells (0.5 × 104/well) are plated in 96-well sterile plastic plates and allowed to attach overnight. Cells are exposed to varying doses of gefitinib, erlotinib, PHA-665752, and NPS-1034 in medium containing 1% FBS. After 72 hours, 15 μL of MTT solution (5 mg/mL) is added to each well and plates are incubated for 4 hours. Crystalline formazan is solubilized with 100 μL of a 10% (w/v) SDS solution for 24 hours. Absorbance at 595 nm is read spectrophotometrically using a microplate reader. |
| Concentrations | ~5 μM |
| Incubation time | 72 h |
| Animal Experiment | |
|---|---|
| Animal models | SCID mice bearing HCC827/GR tumor xenografts |
| Formulation | PBS |
| Dosages | 10 mg/kg, 5 days a week |
| Administration | p.o. |
| Molecular Weight | 551.54 |
| Formula | C31H23F2N5O3 |
| CAS Number | 1221713-92-3 |
| Solubility (25°C) | DMSO: ≥ 40 mg/mL warmed |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Species | Mouse | Rat | Rabbit | Guinea pig | Hamster | Dog |
| Weight (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| Body Surface Area (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km factor | 3 | 6 | 12 | 8 | 5 | 20 |
| Animal A (mg/kg) = Animal B (mg/kg) multiplied by | Animal B Km |
| Animal A Km |
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
| Related c-Met Products |
|---|
| SU 5616
SU 5616 is an organic compound. |
| MET/PDGFRA-IN-2
MET/PDGFRA-IN-2 is a MET and PDGFRA protein inhibitor. |
| MET/PDGFRA-IN-1
MET/PDGFRA-IN-1 is a MET and PDGFRA protein inhibitor (IC50: 36 μM for MET). |
| Canlitinib
Canlitinib is a tyrosine kinase inhibitor, extracted from patent WO2018072614 (IV-2). |
| Norleual TFA
Norleual TFA, an angiotensin (Ang) IV analog, is a hepatocyte growth factor (HGF)/c-Met inhibitor with an IC50 of 3 pM. |
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