NPS-1034 serves as a dual antagonist for AXL and MET, exhibiting IC50 values of 10.3 nM for AXL and 48 nM for MET. In HCC827/ER cells, where AXL's expression and activity are notably heightened, treatment with NPS-1034 successfully curtails its tyrosine phosphorylation. NPS-1034 reduces the viability of MKN45 and SNU638 cell lines, which have high expression levels of the MET gene and phosphorylated MET, with IC50 values of 112.7 nM and 190.3 nM, respectively. Conversely, it inhibits the viability of AGS, KATOIII, NCI-N87, MKN1, MKN28, and MKN74 cell lines with IC50 values ranging from 1 μM to over 10 μM. Treatment with NPS-1034 significantly lowers MET phosphorylation in MKN45 cells, but not in MKN28 cells. It also inhibits HGF-induced MET autophosphorylation in AGS and MKN1 cell lines with IC50 values of less than 10 nM and less than 50 nM, respectively, with 50 nM of NPS-1034 completely blocking HGF-induced MET phosphorylation[1].
NPS-1034 细胞实验
Cell Line
Concentration
Treated Time
Description
References
MIA PaCa-2 cells
0, 20, 80 µM
48 hours
NPS-1034 induces apoptosis in PDAC cells
Int J Mol Sci. 2024 Jun 24;25(13):6919.
BxPC-3 cells
0, 20, 80 µM
48 hours
NPS-1034 induces apoptosis in PDAC cells
Int J Mol Sci. 2024 Jun 24;25(13):6919.
MIA PaCa-2 cells
0, 10, 20, 40, 80, 160 µM
1 day
NPS-1034 dose-dependently reduces the viability and clonogenicity of PDAC cells
Int J Mol Sci. 2024 Jun 24;25(13):6919.
BxPC-3 cells
0, 10, 20, 40, 80, 160 µM
1 day
NPS-1034 dose-dependently reduces the viability and clonogenicity of PDAC cells
Int J Mol Sci. 2024 Jun 24;25(13):6919.
Caki-1
0, 10, 20, 40, 80, 160 µM
24 hours
To evaluate the cytotoxic effects of NPS-1034 on RCC cell lines, showing significant reduction in cell viability
Cells. 2024 Oct 17;13(20):1713.
786-0
0, 10, 20, 40, 80, 160 µM
24 hours
To evaluate the cytotoxic effects of NPS-1034 on RCC cell lines, showing significant reduction in cell viability
Cells. 2024 Oct 17;13(20):1713.
A498
0, 10, 20, 40, 80, 160 µM
24 hours
To evaluate the cytotoxic effects of NPS-1034 on RCC cell lines, showing significant reduction in cell viability
Cells. 2024 Oct 17;13(20):1713.
NTERA2 cells
10, 20, 40, 80, 160 µM
24 hours
To evaluate the effect of NPS-1034 on NTERA2 cell viability, results showed that NPS-1034 reduced cell viability in a dose-dependent manner.
Medicina (Kaunas). 2022 Feb 27;58(3):355.
NCCIT cells
10, 20, 40, 80, 160 µM
24 hours
To evaluate the effect of NPS-1034 on NCCIT cell viability, results showed that NPS-1034 reduced cell viability in a dose-dependent manner.
Medicina (Kaunas). 2022 Feb 27;58(3):355.
HCC4011
1 µM
72 hours
To evaluate the effect of NPS1034 in combination with osimertinib on the sensitivity of high-AXL-expressing EGFR-mutated NSCLC cells, results showed that the combination significantly reduced the viability of HCC4011 cells.
Nat Commun. 2019 Jan 16;10(1):259.
PC-9GXR
1 µM
72 hours
To evaluate the effect of NPS1034 in combination with osimertinib on the sensitivity of high-AXL-expressing EGFR-mutated NSCLC cells, results showed that the combination significantly reduced the viability of PC-9GXR cells.
Nat Commun. 2019 Jan 16;10(1):259.
PC-9
1 µM
72 hours
To evaluate the effect of NPS1034 in combination with osimertinib on the sensitivity of high-AXL-expressing EGFR-mutated NSCLC cells, results showed that the combination significantly reduced the viability of PC-9 cells.
Nat Commun. 2019 Jan 16;10(1):259.
NPS-1034 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Renca-luc lung metastasis model
Oral
10 or 30 mg/kg
Once daily for 5 weeks
To evaluate the inhibitory effects of NPS-1034 on RCC tumor growth in vivo, showing significant alleviation of tumor burden
Cells. 2024 Oct 17;13(20):1713.
Nude mice
PC-9 cell-line-derived xenograft (CDX) model
Oral gavage
50 mg/kg NPS1034 and 5 mg/kg osimertinib
5 days a week for 10 weeks
To evaluate the effect of NPS1034 in combination with osimertinib on high-AXL-expressing EGFR-mutated NSCLC tumors, results showed that the combination significantly inhibited tumor re-growth.
Nat Commun. 2019 Jan 16;10(1):259.
NPS-1034 动物研究
Animal study
NPS-1034 suppresses tumor growth in tumors that express high levels of phosphorylated MET and leads to a notable reduction in tumor vascularization. The expression of α-SMA is also reduced in the tumor sections of mice treated with NPS-1034. Mice treated with NPS-1034 exhibit no significant weight loss, suggesting that the compound is generally well-tolerated[2].
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