NST-628

Cat. No.: HY-158115: FAQs
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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.

For research use only. We do not sell to patients.

NST-628 Chemical Structure

CAS No. : 3002056-30-3

Size	Price	Stock
5 mg	USD 450	Ask For Quote & Lead Time
10 mg	USD 750	Ask For Quote & Lead Time
25 mg	USD 1650	Ask For Quote & Lead Time
50 mg	USD 2550	Ask For Quote & Lead Time
100 mg	USD 3800	Ask For Quote & Lead Time

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Biological Activity
Purity & Documentation
References
Customer Review

Description

In Vitro

NST-628 (100 nM; 2 h) has higher antiproliferative activity in BRAF class II/III mutant cell models compared to other RAF and MEK inhibitors, and it does not promote the formation of BRAF and CRAF heterodimers^[2].
NST-628 (4-100 nM; 48 h) increases the levels of early and late apoptotic cells and reduces the number of live 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Apoptosis Analysis^[2]

Cell Line:	NRAS mutant IPC-298 and SK-MEL-2, NF1 mutant MeWo, and KRAS mutant HCT116 cell
Concentration:	4, 20, 100 nM
Incubation Time:	48 h
Result:	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).

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.

Molecular Weight

488.46

Formula

C₂₂H₁₈F₂N₄O₅S

CAS No.

3002056-30-3

SMILES

FC1=C(OC2=CC=C(C(C)=C(CC3=C(F)C(NS(NC)(=O)=O)=NC=C3)C(O4)=O)C4=C2)N=CC=C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Please store the product under the recommended conditions in the Certificate of Analysis.

Purity & Documentation

Handling Instructions (2659 KB)

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

NST-628 Related Classifications

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Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

NST-6283002056-30-3NST628NST 628Molecular GluesRafMEKRaf kinasesMitogen-activated protein kinase kinaseMAPKKMAP2KInhibitorinhibitorinhibit

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