There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
The RAS/RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways have been identified as promising therapeutic targets for cancer therapy. Over-activation of these pathways and their components including gene mutations has been considered as one of the major causes of melanoma. Mitogen-activated protein kinase (MEK) is a downstream kinase of RAS pathway found in two different forms MEK1/2[2]. APS-2-79 hydrochloride behaves as a kinase suppressor of Ras (KSR)-dependent antagonist of RAF-mediated MEK phosphorylation. APS-2-79 binds directly to KSR2 within the KSR2-MEK1 complex with an IC50 of 120 ± 23 nM for KSR2[3]. APS-2-79 (1 μM) shifts the cell viability dose response to Trametinib in Ras-mutant cell lines HCT-116 and A549, but not BRAF mutant cell lines SK-MEL-239 and A375. Although the cellular effects of APS-2-79 alone are modest, combination analysis over full concentration matrices reveal that kinase suppressor of Ras (KSR)-inactive state (KSRi) synergizes with Trametinib, and other MEK inhibitors, specifically in KRAS mutant cell lines. APS-3-77, and additional control compounds, do not demonstrate Ras-mutant-specific synergy, supporting the hypothesis that the enhanced activity of Trametinib when combined with APS-2-79 depends on co-modulation of KSR[3].
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