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.
LM10 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Myc−/− cells
5 µM
overnight
Limited nuclear translocation of AHR
Genes Dev. 2019 Sep 1;33(17-18):1236-1251.
TDO2+ myofibroblasts
5 μM
3 days
Attenuated the inhibitory states of T cells, restored the T cell antitumor response
J Clin Invest. 2022 Oct 3;132(19):e157649.
Rat brain endothelial cells
100 nM
4 days
To evaluate the effect of LM10 on BBB integrity, found that LM10 significantly increased TEER and reversed IL-1β-induced BBB dysfunction
J Neuroinflammation. 2016 Feb 1;13:25.
Fibroid explants
50μM
48 hours
To investigate the effect of 680C91 on gene expression in fibroid explants, results showed that 680C91 blocked tryptophan-induced expression of CYP1B1, TGF-β3, FN1, CDK2, E2F1, IL8, and SPARC mRNA
Fertil Steril. 2024 Apr;121(4):669-678.
LM10 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6NCrl mice
Rotenone-induced Parkinson’s disease mouse model
Oral
12.5, 25, 50 mg/kg
Once daily for 35 days
Evaluation of LM10 effects on rotenone-induced motor and cognitive dysfunction, dopaminergic cell loss, neuroinflammation, and intestinal dysfunction. Results showed that LM10 improved motor function, reduced dopaminergic cell loss in the substantia nigra, decreased neuroinflammatory markers, and improved intestinal transit and colon length.
FEBS J. 2021 Jul;288(14):4311-4331
C57BL/6 mice
4NQO-induced oral cancer model
Oral gavage
160 mg/kg
Once daily for 4 weeks
Prevented the progression of OSCC malignant transformation
搜索
HazMat Fee +
