LHVS |
Catalog No.GC38809
One-Click Copy Product Info
|
LHVS is a potent, non-selective, irreversible, and cell-permeable cysteine protease and cathepsin inhibitor. LHVS also inhibits T. gondii invasion (IC₅₀=10μM).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 170111-28-1
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
LHVS is a potent, non-selective, irreversible, and cell-permeable cysteine protease and cathepsin inhibitor. LHVS also inhibits T. gondii invasion (IC₅₀=10μM)[1-2]. Through its vinyl sulfone moiety, LHVS covalently modifies the thiol group at the active site of cathepsin S, thereby achieving high selectivity in inhibiting cathepsin S activity. LHVS can be used in research related to neuropathic pain and the autophagy/lysosomal degradation pathway[3-4].
In vitro, treatment of the B-lymphoblastoid cell line HOM2 with LHVS (1–5nM) for 1 hour specifically inhibited cathepsin S activity, prevented complete proteolysis of the invariant chain, and significantly reduced the formation of SDS-stable αβ dimers[5]. Treatment of MCF7 tumor cells and U-937 macrophage-like cells with LHVS (10nM) for 72 hours did not show a significant effect on cell proliferation[6].
In vivo, a single intracerebroventricular (i.c.v.) injection of LHVS (10–50nM; 6μL) was administered to male ICR mice 10 minutes before the induction of traumatic brain injury (TBI). LHVS significantly reduced the levels of the pro-inflammatory cytokines IL-1β and TNF-α in the injured cortex, alleviated brain edema at 24 hours post-TBI, suppressed neuronal degeneration in the cortex, and improved neurobehavioral scores in mice at 24 hours after injury[7]. Daily intraperitoneal injection of LHVS (25mg/kg), starting from day 0 to day 15 of MOG₃₅₋₅₅ immunization to induce experimental autoimmune encephalomyelitis (EAE), was administered to both wild-type (WT) and cathepsin S-deficient (Cat S⁻/⁻) C57BL/6 mice. LHVS completely prevented the clinical onset of MOG₃₅₋₅₅-induced EAE in both WT and Cat S⁻/⁻ mice and significantly reduced the number of infiltrating macrophages, microglia, CD4⁺ T cells, CD8⁺ T cells, and B cells in the spinal cord[8].
References:
[1] Wilson SR, Peters C, Saftig P, et al. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009 Jan 23;284(4):2584-92.
[2] Teo CF, Zhou XW, Bogyo M, et al. Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion. Antimicrob Agents Chemother. 2007 Feb;51(2):679-88.
[3] Barclay J, Clark AK, Ganju P, et al. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain. 2007 Aug;130(3):225-234.
[4] Fujii H, Ivison SM, Shimizu H, et al. Inhibition of cathepsin S reduces allogeneic T cell priming but not graft-versus-host disease against minor histocompatibility antigens. Biol Blood Marrow Transplant. 2012 Apr;18(4):546-56.
[5] Riese RJ, Wolf PR, Brömme D, et al. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity. 1996 Apr;4(4):357-66.
[6] Mitrović A, Senjor E, Jukić M, et al. New inhibitors of cathepsin V impair tumor cell proliferation and elastin degradation and increase immune cell cytotoxicity. Comput Struct Biotechnol J. 2022 Aug 28;20:4667-4687.
[7] Xu J, Wang H, Ding K, et al. Inhibition of cathepsin S produces neuroprotective effects after traumatic brain injury in mice. Mediators Inflamm. 2013;2013:187873.
[8] Allan ER, Yates RM. Redundancy between Cysteine Cathepsins in Murine Experimental Autoimmune Encephalomyelitis. PLoS One. 2015 Jun 15;10(6):e0128945.
| Cell experiment [1]: | |
|
Cell lines |
HOM2 cells (human B lymphoblastoid cell line) |
|
Preparation Method |
HOM2 cells were maintained in RPMI medium supplemented with 10% fetal bovine serum (FBS), penicillin, streptomycin, and glutamine. HOM2 cells were preincubated with LHVS (1-5nM) prior to a pulse-chase metabolic labeling experiment with [³⁵S]methionine/cysteine. |
|
Reaction Conditions |
1-5nM; 1h. |
|
Applications |
LHVS inhibited cathepsin S in HOM2 cells. LHVS prevented the complete proteolysis of the invariant chain (li), resulting in the accumulation of a class II-associated 13kDa li fragment. Consequently, the formation of SDS-stable αβ dimers (representing peptide-loaded complexes) was markedly reduced. |
| Animal experiment [2]: | |
|
Animal models |
Male ICR mice |
|
Preparation Method |
Mice received a single intracerebroventricular (i.c.v.) injection of LHVS (10, 30, or 50nM in 6µL of 20% Cremophor EL/saline vehicle) 10 minutes before the induction of traumatic brain injury (TBI) using a weight-drop model. Mice were sacrificed at 24 hours post-TBI for the analysis of brain tissue (cytokines, edema, neuronal degeneration) and their neurobehavioral function was evaluated at 24 hours and 3 days. |
|
Dosage form |
10, 30, or 50nM (in 6µL vehicle); i.c.v.; single injection 10 min pre-TBI. |
|
Applications |
LHVS pretreatment significantly reduced the levels of proinflammatory cytokines (IL-1β and TNF-α) in the injured cortex, alleviated brain edema, suppressed neuronal degeneration in the cortex, and improved neurobehavioral scores at 24 hours after TBI |
|
References: |
|
| Cas No. | 170111-28-1 | SDF | |
| Canonical SMILES | O=C(N1CCOCC1)N[C@H](C(N[C@@H](CCC2=CC=CC=C2)/C=C/S(=O)(C3=CC=CC=C3)=O)=O)CC(C)C | ||
| Formula | C28H37N3O5S | M.Wt | 527.68 |
| Solubility | DMSO : 100 mg/mL (189.51 mM; Need ultrasonic) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.8951 mL | 9.4754 mL | 18.9509 mL |
| 5 mM | 379 μL | 1.8951 mL | 3.7902 mL |
| 10 mM | 189.5 μL | 947.5 μL | 1.8951 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 2 reference(s) in Google Scholar.)