| Identification | Back Directory | [Name]
Sulfamide, N-[3-fluoro-4-[[7-[(3-fluoro-2-pyridinyl)oxy]-4-methyl-2-oxo-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N′-methyl- | [CAS]
3002056-30-3 | [Synonyms]
Sulfamide, N-[3-fluoro-4-[[7-[(3-fluoro-2-pyridinyl)oxy]-4-methyl-2-oxo-2H-1-benzopyran-3-yl]methyl]-2-pyridinyl]-N′-methyl- | [Molecular Formula]
C22H18F2N4O5S | [MOL File]
3002056-30-3.mol | [Molecular Weight]
488.47 |
| Chemical Properties | Back Directory | [Boiling point ]
630.7±65.0 °C(predicted) | [density ]
1.497±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted) | [form ]
Solid | [pka]
6.60±0.50(predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
NST-628 is a brain-permeable MAPK pathway molecule glue that inhibits RAF phosphorylation and MEK activation. NST-628 also binds RAF and prevents the formation of BRAF-CRAF and BRAF-ARAF heterodimers, effectively inhibiting the RAS-MAPK pathway. NST-628 inhibits RAS- and RAF-driven cancers and demonstrated potent inhibition in mutant KRAS, NRAS, BRAF class II/III, and NF1-mutant tumors[1]. | [in vivo]
qd: once daily ; b.i.d: twice daily
NST-628 (p.o.; 3 mg/kg; qd, 5 mg/kg; qd, or 1.5 mg/kg; b.i.d) can significantly slow tumor growth in mouse models with KRAS and NRAS mutations. NST-628 also leads to tumor regressions in the SK-MEL-2-luc model[2].
NST-628 (i.g.; 0.3-3 mg/kg; qd; 18-20 days) inhibites the RAS-MAPK pathway in mice in a dose-dependent manner. NST-628 also exhibites strong antitumor activity in the MeWo-luc model[2].
NST-628 (i.g.; 2 mg/kg; qd; 26 days) slows tumor growth and effectively inhibits the RAS–MAPK pathway in NCI-H23 KRASG12C-mutant lung adenocarcinoma model[2].
| Animal Model: | mouse models with KRAS and NRAS mutations [2] | | Dosage: | 3 mg/kg; qd, 5 mg/kg; qd, and 1.5 mg/kg; b.i.d | | Administration: | p.o. | | Result: | 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)). |
| Animal Model: | NCI-H23 KRASG12C-mutant lung adenocarcinoma model [2] | | Dosage: | 2 mg/kg; 26 days | | Administration: | i.g.; qd | | Result: | The combination of NST-628 and sotorasib resulted in deep tumor regressions that were durable for the 40-day study duration.The combination led to a significant decrease in phospho-ERK levels. |
| [References]
[1] Ryan M B, et al. Abstract ND10: NST-628 is a novel, potent, fully brain-penetrant MAPK pathway molecular glue that inhibits RAS-and RAF-driven cancers[J]. Cancer Research, 2024, 84(7_Supplement): ND10-ND10.
[2] Meagan B et al. The Pan-RAF–MEK Nondegrading Molecular Glue NST-628 Is a Potent and Brain-Penetrant Inhibitor of the RAS–MAPK Pathway with Activity across Diverse RAS- and RAF-Driven Cancers. Cancer Discov 2024 |
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| Company Name: |
ChemOrigin Pharm
|
| Tel: |
021-15026428026 15026428026 |
| Website: |
chemorigin.com/ |
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