| Size | Price | Stock | Qty |
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| ln Vitro |
NST-628 (100 nM; 2 h) exhibited higher antiproliferative activity than other RAF and MEK inhibitors in BRAF class II/III mutant cell models and did not promote heterodimer formation of BRAF and CRAF[2]. NST-628 (4-100 nM; 48 h) increased the levels of early and late apoptotic cells and reduced viable cells in a dose-dependent manner in NRAS mutant IPC-298 and SK-MEL-2, NF1 mutant MeWo, and KRAS mutant HCT116 cell lines[2].
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| ln Vivo |
qd: once daily; bid: twice daily NST-628 (po; 3 mg/kg; qd, 5 mg/kg; qd or 1.5 mg/kg; bid) is significant in tumor models with KRAS and NRAS mutations Slows tumor growth. Causes tumor regression in the SK-MEL-2-luc model [2]. NST-628 (ig; 0.3-3 mg/kg; qd; 18-20 days) inhibits the RAS-MAPK pathway in a dose-dependent manner in mice. It has strong anti-tumor activity in the MeWo-luc model [2]. NST-628 (ig; 2 mg/kg; qd; 26 days) slows tumor growth in the NCI-H23-KRASG12C mutant lung adenocarcinoma model. Effectively inhibits the RAS–MAPK pathway [2].
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| Cell Assay |
Apoptosis Analysis[2]
Cell Types: NRAS mutant IPC-298 and SK-MEL-2, NF1 mutant MeWo, and KRAS mutant HCT116 cell Concentration: 4, 20, 100 nM Incubation Duration: 48 h Experimental Results: 100 nmol/L NST-628 induced the highest level of apoptosis. Equivalent to the MEK inhibitor Trametinib (HY-10999) and showed greater potency than the MEK inhibitor Cobimetinib (HY-13064), the RAF-MEK inhibitor Avutometinib (HY-18652) and the type II RAF inhibitors Belvarafenib (HY-109080) and Tovorafenib (HY-15246). |
| Animal Protocol |
Animal/Disease Models:mouse models with KRAS and NRAS mutations [2]
Doses: 3 mg/kg; qd, 5 mg/kg; qd, and 1.5 mg/kg; b.i.d Route of Administration: p.o. Experimental Results: Significantly inhibited MEK and ERK phosphorylation in tumor tissues. Demonstrated superior anti-tumor efficacy and better tolerability than existing MEK inhibitors (e.g. Cobimetinib (HY-13064)) and RAF inhibitors (e.g. Belvarafenib (HY-109080)). |
| References |
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| Molecular Formula |
C22H18F2N4O5S
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|---|---|
| Molecular Weight |
488.46
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| Exact Mass |
488.096
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| CAS # |
3002056-30-3
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| Appearance |
Solid powder
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| Density |
1.497±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
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| Boiling Point |
630.7±65.0 °C(predicted)
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| LogP |
2.7
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| SMILES |
CC1=C(C(OC2=CC(=CC=C21)OC1N=CC=CC=1F)=O)CC1=CC=NC(=C1F)NS(=O)(=O)NC
|
| InChi Key |
YQSZJOABXRROQR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H18F2N4O5S/c1-12-15-6-5-14(32-21-17(23)4-3-8-27-21)11-18(15)33-22(29)16(12)10-13-7-9-26-20(19(13)24)28-34(30,31)25-2/h3-9,11,25H,10H2,1-2H3,(H,26,28)
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| Chemical Name |
3-[[3-fluoro-2-(methylsulfamoylamino)pyridin-4-yl]methyl]-7-(3-fluoropyridin-2-yl)oxy-4-methylchromen-2-one
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (204.73 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.12 mM)(Saturation unknown) in 10% DMSO 40% PEG300 5% Tween-80 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution, add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix well; then add 50 μL Tween-80 to the above system and mix well; then add 450 μL saline to make it 1 mL. *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0473 mL | 10.2363 mL | 20.4725 mL | |
| 5 mM | 0.4095 mL | 2.0473 mL | 4.0945 mL | |
| 10 mM | 0.2047 mL | 1.0236 mL | 2.0473 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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