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
FAAH (fatty acid amide hydrolase) is an intracellular membranebound enzyme that principally degrade the endocannabinoid anandamide. It utilizes unusual catalytic triad Ser-Ser-Lys to degrade and inactivate fatty acid amide family of signaling lipids, including the endogenous cannabinoid ligands N-arachidonoylethanolamine (Anandamide, AEA) and 2-arachidonoyl glycerol (2-AG). PF-3845 is an irreversible, highly efficacious and selective FAAH inhibitor with Ki value of 0.23μM. Preincubation with PF-3845 for 1h inhibited hFAAH activity for hydrolysis of its substrate AAMCA. Administration of PF-3845 at dose of 10mg/kg, i.p., for 1-24h inactivated FAAH in the brain of mice as judged by competitive activity-based protein profiling with the serine hydrolase-directed probe fluorophosphonate (FP)-rhodamine. PF-3845-treated mice (10 mg/kg, i.p.) also showed dramatic elevations in brain levels of AEA and other NAEs (N-pamitoyl ethanolamine [PEA] and N-oleoyl ethanolamine [OEA]. PF-3845-treated animals did not show changes in the levels of 2-AG in brain or liver, suggesting that distinct enzymes regulate this endocannabinoid in vivo. Administration of PF-3845 produced cannabinoid receptor-dependent reductions in inflammatory pain in vivo. Oral administration of PF-3845 at 10 and 30mg/kg caused a dose-dependent inhibition of mechanical allodynia and inhibited pain response in a rat model of inflammatory pain.
作用机制
PF-3845 is a covalent inhibitor that carbamylates FAAH’s serine nucleophile.
PF-3845 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Bone marrow macrophages (BMMs)
1-10 μM
4 days
PF-3845 significantly inhibited RANKL-induced osteoclast differentiation, reduced the formation of TRAP-positive multinucleated cells, and decreased the expression of NFATc1 and osteoclast-specific marker genes.
Int J Mol Sci. 2021 Feb 15;22(4):1915.
Mouse primary astrocyte and microglia co-culture
10 µM
1 hour
To assess the effect of PF-3845 on NAE levels, results showed that PF-3845 increased NAE levels.
Neurotherapeutics. 2021 Jul;18(3):1815-1833.
Prefrontal cortex neurons
1 μM
5 minutes
To evaluate the effects of PF3845 on inhibitory GABAergic neurotransmission. PF3845 significantly decreased the frequency of sIPSCs and mIPSCs, indicating it reduced GABA release via CB1R-related mechanisms.
Cells. 2022 Mar 2;11(5):857.
PF-3845 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
TNBS- and DSS-induced colitis models
Intraperitoneal, oral, and intracolonic administration
10 mg/kg
Once or twice daily for 3 days (TNBS model) or 7 days (DSS model)
To assess the anti-inflammatory action of PF-3845 and its effect on endocannabinoid and related lipid metabolism during experimental colitis. Results showed that PF-3845 exhibited significant anti-inflammatory effects in the TNBS-induced colitis model but was ineffective in the DSS model.
J Crohns Colitis. 2014 Sep;8(9):998-1009
Male ICR (CD-1) mice
Anxiety-like behavior model
Intraperitoneal injection
1 mg/kg
Two hours prior to behavioral testing
PF-3845 partially prevented the anxiogenic effects of restraint stress exposure
Biol Psychiatry. 2017 Oct 1;82(7):488-499
Mice
LPS-induced tactile allodynia model
Intraperitoneal injection
1–10 mg/kg
Single dose, 2 hours before testing
PF-3845 reversed LPS-induced tactile allodynia by inhibiting FAAH to increase AEA levels, and the effect depended on the activation of both CB1 and CB2 receptors.
Br J Pharmacol. 2012 Apr;165(8):2485-96
ICR mice
Morphine-dependent mouse model
Intraperitoneal injection
10 mg/kg
Single administration, observed for 8 hours
PF-3845 significantly attenuated a subset of spontaneous morphine withdrawal signs, including head shakes, paw flutters, and jumping behavior (only at the 6-h time point), but did not affect the incidence of diarrhea or weight loss.
Neuropsychopharmacology. 2013 May;38(6):1039-49
ICR (CD-1) mice
Anxiety-like behavior model
Intraperitoneal injection
0.1, 1, and 10 mg/kg
Single dose, 2 hours before behavioral testing
PF-3845 was able to prevent restraint stress-induced anxiety in the light–dark box assay when administered before stress exposure, but had no effect under non-stressed conditions.
Transl Psychiatry. 2018 Apr 26;8(1):92
C57BL/6J female mice
Experimental autoimmune encephalomyelitis (EAE) model
Intraperitoneal injection
10 mg/kg
Once daily, from day 3 to day 30 post immunization
To evaluate the effect of FAAH inhibition on EAE, results showed that PF-3845 had no significant effect on the severity of EAE.
Neurotherapeutics. 2021 Jul;18(3):1815-1833.
Mice
Carrageenan-induced inflammatory pain model
Intraperitoneal injection
1, 3, or 10 mg/kg
Single administration
PF-3845 significantly attenuated carrageenan-induced paw edema and mechanical allodynia.
Life Sci. 2013 Mar 19;92(8-9):498-505
C57BL/6J mice
Endotoxin or cold environment-induced hypothermia model
Intraperitoneal injection
10 mg/kg
Single administration
To evaluate the effect of PF-3845 on endotoxin or cold environment-induced hypothermia, results showed that PF-3845 had no effect on either type of hypothermia.
J Neuroimmune Pharmacol. 2015 Jun;10(2):364-70
Mice
FAAH(+/+) mice
Intraperitoneal injection
10 mg/kg
Single dose, sacrificed after 3 hours
To evaluate the inhibitory effect of PF-3845 on FAAH and its impact on NAE and NAT metabolism. Results showed that PF-3845 significantly inhibited FAAH activity, leading to substantial accumulation of anandamide and other NAEs in brain, liver, and testis.
J Lipid Res. 2011 Feb;52(2):337-44
Mice
Ligature-induced periodontitis model
Intraperitoneal injection
10 mg/kg
Once daily for 6 days
PF-3845 significantly reduced alveolar bone loss and the number of osteoclasts in experimental periodontitis.
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