[CAS NO. 913376-84-8] SYN1143
PRODUCTS SPECIFICATIONS [913376-84-8]
DESCRIPTION [913376-84-8]
Overview
| MDL | MFCD22631502 |
|---|---|
| Molecular Weight | 556.58 |
| Molecular Formula | C31H29FN4O5 |
| SMILES | O=C(C1=C(C)N(CC(C)(O)C)N(C2=CC=CC=C2)C1=O)NC3=CC=C(OC4=CC=NC5=CC(OC)=CC=C45)C(F)=C3 |
Summary
SYN1143 is a potent, selective and orally active dual inhibitor of c-Met/RON , with IC 50 s of 4 and 9 nM, respectively. SYN1143 has weak inhibitory activity on Lck , Tie2 , Src , and BTK with IC 50 s ranging from 160 to 710 nM. SYN1143 can be used for the research of cancers that RON and c-Met are activated [1] .
IC50 & Target
|
RON 9 nM (IC 50 ) |
In Vitro
SYN1143 (Compound I) (10-1000 nM; 1 h) inhibits c-Met-mediated signaling and functional activity in HT-29 and BxPC3 cells
[1]
.
SYN1143 (10-1000 nM; 1 h) inhibits RON-mediated signaling and functional activity in NIH3T3 RON and BxPC3 cells
[1]
.
SYN1143 (0.3-30 μM; 2 h or 3 d) inhibits c-Met signaling and cell proliferation in MC
3
T
3
-E
1
and C
3
H
10
T
1/2
cells
[2]
.
SYN1143 (0.3-2 μM; 4-12 d) potentiates osteogenic differentiation of precursor cells
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
Western Blot Analysis [1]
| Cell Line: | HT-29 and BxPC3 cells |
| Concentration: | 10, 30, 100, 300, 1000 nM |
| Incubation Time: | 1 hours |
| Result: | Inhibited HGF-mediated c-Met phosphorylation and downstream signaling in a dose-dependent manner in both cell lines. |
In Vivo
SYN1143 (10-100 mg/kg; p.o. for 22 d) inhibits the growth of c-Met-dependent and constitutively active RON-expressing tumors in mice
[1]
.
SYN1143 (20-50 μg; transferred into calvarial defects) stimulates bone formation in critical-sized defects of mouse calvarial bone
[2]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female CD1 nu/nu mice (6-8 weeks) bearing NIH3T3 TPR-Met s.c. tumors [1] |
| Dosage: | 10, 30, 100 mg/kg |
| Administration: | Oral gavage either once or twice daily for 22 days |
| Result: |
Significantly inhibited tumor growth at doses of 30 or 100 mg/kg once daily or at 30 mg/kg twice daily.
Completely inhibited tumor growth at a dose of 100 mg/kg once daily. Did not adversely affect body weight. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : 100 mg/mL ( 179.67 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.7967 mL | 8.9834 mL | 17.9669 mL |
| 5 mM | 0.3593 mL | 1.7967 mL | 3.5934 mL |
| 10 mM | 0.1797 mL | 0.8983 mL | 1.7967 mL |
References
- [1] Zhang Y, et, al. Identification of a novel recepteur d'origine nantais/c-met small-molecule kinase inhibitor with antitumor activity in vivo. Cancer Res. 2008 Aug 15;68(16):6680-7.
- [2] Kim JW, et, al. Chemical inhibitors of c-Met receptor tyrosine kinase stimulate osteoblast differentiation and bone regeneration. Eur J Pharmacol. 2017 Jul 5;806:10-17.
Synonyms