| CAS NO: | 1221713-92-3 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 10mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
| Molecular Weight (MW) | 551.54 |
|---|---|
| Formula | C31H23F2N5O3 |
| CAS No. | 1221713-92-3 |
| Storage | -20℃ for 3 years in powder form |
| -80℃ for 2 years in solvent | |
| Solubility (In vitro) | DMSO: 100 mg/mL (181.3 mM) |
| Water: <1 mg/mL | |
| Ethanol: 4 mg/mL (7.3 mM) | |
| Solubility (In vivo) | PBS: 11mg/mL |
| Synonyms | NPS-1034; NPS 1034; NPS1034; Chemical Name: N-(3-fluoro-4-((3-phenyl-1H-pyrrolo[2,3-b]pyridin-4-yl)oxy)phenyl)-2-(4-fluorophenyl)-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazole-4-carboxamide. InChi Key: RGAZVGZUBCFHRJ-UHFFFAOYSA-N InChi Code: InChI=1S/C31H23F2N5O3/c1-18-27(31(40)38(37(18)2)22-11-8-20(32)9-12-22)30(39)36-21-10-13-25(24(33)16-21)41-26-14-15-34-29-28(26)23(17-35-29)19-6-4-3-5-7-19/h3-17H,1-2H3,(H,34,35)(H,36,39) SMILES Code: O=C(C1=C(C)N(C)N(C2=CC=C(F)C=C2)C1=O)NC3=CC=C(OC4=C5C(NC=C5C6=CC=CC=C6)=NC=C4)C(F)=C3 |
| In Vitro | In vitro activity: 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. Kinase Assay: The in vitro NPS-1034 profile of inhibition of RTKs is analyzed using RTK assay kits according to the manufacturer's protocols. Cell Assay: To perform the MTT assay, cells (0.5 × 104/well, HCC827/GR, HCC-78 and H820 cells) 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. |
|---|---|
| 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. |
| Animal model | SCID mice bearing HCC827/GR tumor xenografts |
| Formulation & Dosage | Dissolved in PBS; 10 mg/kg; oral gavage |
| References | Cancer Res. 2014 Jan 1;74(1):253-62; Invest New Drugs. 2014 Jun;32(3):389-99. |
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