Background
IC50: 56 nM
SID 26681509 is a potent and reversible human cathepsin L inhibitor.
The cathepsins have been found to comprise a family of lysosomal protease enzymes whose primary functions, such as protein degradation, play a keyl role in normal cellular homeostasis. Overexpression of cathepsin L and/or abnormal activity has been implicated in a number of disease states.
In vitro: SID 26681509 was found to inhibit human cathepsin L with an IC50 of 56 nM. After preincubation with enzyme for 1, 2, and 4 h before substrate addition, SID 26681509 showed increasing potency, with IC50 values falling to 7.5, 4.2, and 1.0 nM, respectively, indicating a slow onset of inhibition. SID 26681509 was also observed to be nontoxic to human aortic endothelial cells up to 100 μM. SID 26681509 was active in an in vitro propagation assay against P. falciparum with an IC50 of 15.4 μM. Additionally, the thiocarbazate inhibitor was toxic toward L. major promastigotes with an IC50 of 12.5 μM [1].
In vivo: SID 26681509 showed a lack of toxicity to zebrafish in a live organism assay at 100 μM [1].
Clinical trial: N/A
Reference:
[1] Shah PP,Myers MC,Beavers MP,Purvis JE,Jing H,Grieser HJ,Sharlow ER,Napper AD,Huryn DM,Cooperman BS,Smith AB 3rd,Diamond SL.? Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L. Mol Pharmacol.2008 Jul;74(1):34-41.
Protocol
|
Cell experiment [1]:
|
|
Cell lines
|
human aortic endothelial cells
|
|
Preparation method
|
The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.
|
|
Reacting condition
|
100 μM, 37°C for 24 h
|
|
Applications
|
SID 26681509 (100 μM) was non-toxic to human aortic endothelial cells. SID 26681509 was active in an in vitro propagation assay against P. falciparum with an IC50 of 15.4 ± 0.6 μM. SID 26681509 was toxic toward L. major promastigotes with an IC50 of 12.5 ± 0.6 μM.
|
|
Animal experiment [1]:
|
|
Animal models
|
zebrafish
|
|
Dosage form
|
100 μM
|
|
Application
|
SID 26681509 (100 μM) demonstrated a lack of toxicity to zebrafish in a live organism assay.
|
|
Other notes
|
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.
|
|
参考文献:
[1]. Shah P P, Myers M C, Beavers M P, et al. Kinetic characterization and molecular docking of a novel, potent, and selective slow-binding inhibitor of human cathepsin L[J]. Molecular pharmacology, 2008, 74(1): 34-41.
|
没有评价数据