NPS-1034

SKU: orb1300357

Description

NPS-1034 is a potent small molecule inhibitor targeting both Met and Axl kinases, exhibiting IC50 values of 48 nM and 10.3 nM, respectively. It is a valuable research tool for studying oncogenic signaling in vitro and has shown efficacy in reducing tumor growth in preclinical in vivo cancer models.

Research Area

Cell Biology, Neuroscience, Signal Transduction

Key Properties

• CAS Number: 1221713-92-3
• MW: 551.54
• Purity: 97.86% (May vary between batches)
• Formula: C₃₁H₂₃F₂N₅O₃
• SMILES: Cc1c(C(=O)Nc2ccc(Oc3ccnc4[nH]cc(-c5ccccc5)c34)c(F)c2)c(=O)n(-c2ccc(F)cc2)n1C
• Target: c-Met/HGFR,Apoptosis,TAM Receptor
• Solubility: H2O:< 1 mg/mL (insoluble or slightly soluble);DMSO:93 mg/mL (168.62 mM);Ethanol:4 mg/mL (7.25 mM)

Bioactivity

• Target IC50:
  Axl:10.3 nM
• In Vivo:
  In SCID mice bearing HCC827/GR tumor xenografts, NPS-1034 (10 mg/kg, p.o.) decreases tumor growth, and the combination of gefitinib and NPS-1034 results in enhanced tumor growth inhibition via the inhibition of tumor proliferation and the induction of apoptosis. 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.
• In Vitro:
  In HCC827/GR cells, NPS-1034 does not show significant antiproliferative effects, while overcomes gefitinib resistance by inhibiting the phosphorylation of MET, Akt, and Erk. In H820 cells, NPS-1034 enhances sensitivity to EGFR-TKIs. In HCC78 cells, NPS-1034 inhibits ROS1 activity and cell proliferation. In addition, a combination of gefitinib and NPS-1034 enhances cell death by inducing caspase-3 and PARP-1 cleavage. NPS-1034 inhibits the viability of the MKN45 and SNU638 cell lines, which highly express the MET gene and p-MET, with IC50 of 112.7 and 190.3 nmol, respectively.
• Cell Research:
  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.(Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

cMet, c-Met, cMet/HGFR, c-Met/HGFR, Axl, AXL, Apoptosis, Inhibitor, HGFR, Met, inhibit, NPS1034, NPS-1034, NPS 1034, Mer, Tyro3, TAM Receptor, TAMReceptor

Compound Identifiers

PubChem CID

46194178