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
Tryptophan-2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are the enzymes controlling the rate-limiting step of the catabolism of tryptophan to immunosuppressive and neuroactive kynurenines, a key metabolic pathway regulating immune responses and neurotoxicity . LM10 can selective inhibit human and mouse TDO with IC50 values of 0.62 and 2 μM, respectively, which display good TDO inhibition with Ki of 5.5 μM. LM10 with a concentration of 1 mg/mL dissolved was given ad libitum to DBA/2 mice in the drinking water of 4 mL/mice/day, plasma concentration was detected from 60-136μM, suggesting a higher oral bioavailability. LM10 was also proved to be highly selective for TDO as, at 10 μM, none of the investigated systems are significantly inhibited. Furthermore, LM10 does not display any inhibitory potency on IDO at all. In an In vivo efficacy study, treatment of immunized mice with LM10 at 160 (mg/kg)/day prevented the growth of TDO-expressing P815 tumor cells . LM10 also showed no obvious signs of toxicity after more than 100 days of systemic administration of LM10 and no significant difference between treated and untreated mice for their plasma level of ALAP, γ-GT, ALAT and ASAT, all of which remained within the normal range. To determine whether the antitumor effects of LM10 resulted only from promoting tumor rejection or whether LM10 also had a direct effect on tumor cells, immunodeficient RAG2 knockout mice with TDO-expressing P815 cells was treated with LM10, while tumor growth was not affected by LM10 treatment indicating that the effect of LM10 was dependent on the immune system in this model.
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