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
Tofacitinib Citrate is the citrate form of Tofacitinib. Tofacitinib is an ATP-competed inhibitor of JAK with IC50 values of 3.2±1.4 nM, 4.1±0.4 nM, 1.6±0.2 nM, 34.0±6.0 nM for JAK1, JAK2, JAK3 and TYK2 in in vitro enzyme assays. It competes with ATP for binding to the active site of the kinase domain of JAKs with Ki values of 0.68 ± 0.12 nM (JAK1), 0.99 ± 0.04 nM (JAK2), 0.24 ± 0.02 nM (JAK3) and 4.39 ± 0.27 nM (TYK2). Tofacitinib potently inhibits multiple cytokine activated JAK/STAT signaling pathways in normal human, mouse or rat whole blood with IC50s below 200 nM. Selectivity assessed in mouse and rat whole blood shows that tofacitinib appears to be more potently to JAK1 and JAK3. In cell assays, tofacitinib inhibits human total myeloid and CFU-G colony formation with IC50s of 0.87 and 0.93 μM. In AIA rats, tofacitinib treatment can decrease paw volume and disease-elevated neutrophil count to normal range compared to vehicle treated control rats. Tofacitinib treatment also dose-dependently decreased both IL-17 and IL-6 of the AIA-induced increase compared to control levels with an approximately 80% inhibition. It significantly inhibits the AIA-induced increase in maturing myeloid cells by approximately 50% at the 10 mg/kg dose[6]. Tofacitinib has been approved by the U.S. Food and Drug Administration and European Medicines Agency for the treatment of rheumatoid arthritis (RA), psoriatic arthritis and ulcerative colitis[2].
Tofacitinib/托法替尼 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Human Rheumatoid Arthritis Synovial Fibroblasts (RASFs)
5 µM
2 h
Inhibition of IL-6/IL-6R-induced JAK/STAT signaling pathway
Front Immunol. 2021 Nov 2;12:746503.
Bone marrow-derived macrophages (BMDM)
300 nM
24, 48, and 96 h
To evaluate the effect of Tofacitinib on TNF-α and IL-1β expression in M.tb-infected BMDM cells. Results showed that BMDM cells from C3HeB/FeJ mice expressed significantly lower levels of TNF-α and IL-1β after infection compared to BALB/c mice. The addition of Tofacitinib did not alter cytokine levels.
EBioMedicine. 2015 Jul 14;2(8):868-73.
CTL effectors from C3H/HeJ mice
50 nM
96 h
Tofacitinib blocked IL-15–triggered pSTAT5 activation and inhibited IL-15-induced upregulation of granzyme B and IFN-γ expression.
Nat Med. 2014 Sep;20(9):1043-9.
NK-S1
1.0 μM
96 h
To detect the effect of Tofacitinib on cell cycle and apoptosis, the results showed that Tofacitinib induced G1 cell cycle arrest and cell death
Leukemia. 2018 May;32(5):1147-1156.
PBMCs
150 nM
4 days
To investigate the inhibitory effect of Tofacitinib on IL-7-induced expansion of CD28- CTLs. The results showed that Tofacitinib significantly inhibited the expansion of CD4+CD28- CTLs and CD8+CD28- CTLs induced by IL-7.
Front Immunol. 2022 Jul 7;13:922307.
CD3+ peripheral T cells
10–500 nM
3 days
Inhibited T cell proliferation, dose-dependently reduced WST-1 conversion to formazan
To evaluate the efficacy of Tofacitinib as an adjunctive therapy in standard TB chemotherapy. Results showed that BALB/c mice receiving Tofacitinib adjunctive therapy achieved apparent lung sterilization within 16 weeks, while the standard treatment group required 24 weeks. However, Tofacitinib did not shorten the time to achieve relapse-free cure. In C3HeB/FeJ mice, Tofacitinib adjunctive therapy showed no effect.
EBioMedicine. 2015 Jul 14;2(8):868-73.
C3H/HeJ mice
Alopecia areata model
Subcutaneous osmotic pump
15 mg/kg
Once daily for 12 weeks
Tofacitinib prevented the development of alopecia areata and blocked the expansion of CD8+NKG2D+ T cells in the skin.
Nat Med. 2014 Sep;20(9):1043-9.
Mice
NK-S1 subcutaneous xenograft model
Intraperitoneal injection
25 mg/kg and 50 mg/kg
Once daily for 14 days
To evaluate the anti-tumor effect of PRN371 in the NK-S1 subcutaneous xenograft model, results showed that PRN371 significantly inhibited tumor growth
Leukemia. 2018 May;32(5):1147-1156.
Mice
Pdcd1−/− mice
Intraperitoneal injection
15 mg/kg
Once daily for 3 days
To investigate the effect of Tofacitinib on the number and function of KLRG1+ ILC-2 cells, it was found that Tofacitinib significantly reduced the number of KLRG1+ ILC-2 cells and IL-13 cytokine production
J Exp Med. 2017 Jun 5;214(6):1663-1678
BALB/c mice
DSS-induced colitis model
Oral
30 mg/kg
Twice daily, starting from day 4 until the end of the experiment
搜索
HazMat Fee +
