| Identification | Back Directory | [Name]
LHVS | [CAS]
170111-28-1 | [Synonyms]
LHVS
K-110717 (LHVS)
N2-(4-Morpholinylcarbonyl)-N-[(1E,3S)-5-phenyl-1-(phenylsulfonyl)-1-penten-3-yl]-L-leucinamide
4-Morpholinecarboxamide, N-[(1S)-3-methyl-1-[[[(1S,2E)-1-(2-phenylethyl)-3-(phenylsulfonyl)-2-propen-1-yl]amino]carbonyl]butyl]- | [Molecular Formula]
C28H37N3O5S | [MDL Number]
MFCD32201152 | [MOL File]
170111-28-1.mol | [Molecular Weight]
527.68 |
| Chemical Properties | Back Directory | [Boiling point ]
822.7±65.0 °C(Predicted) | [density ]
1.195±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Soluble in DMSO | [form ]
Solid | [pka]
12.50±0.20(Predicted) | [color ]
White to off-white | [InChIKey]
YUMYYTORLYHUFW-MSKIIMLESA-N | [SMILES]
O=C(N[C@@H](CC(C)C)C(N[C@H](/C=C/S(=O)(C1=CC=CC=C1)=O)CCC2=CC=CC=C2)=O)N3CCOCC3 |
| Hazard Information | Back Directory | [Uses]
LHVS is a potent, non-selective, irreversible, cell-permeable cysteine protease and cathepsin inhibitor. LHVS decreases actin ring formation. LHVS inhibits T. gondii invasion with an IC50 of 10 μM[1][2][3]. | [Biological Activity]
LHVS is an irreversiblepotent and selective cathepsin S inhibitor (CatS Ki = 5.9 nM; CatO2/L/B Ki = 0.23/0.72/39 μMCruzain Ki = 0.22 μM) th at targets CatS active site thiol for covalent modification via its vinyl sulfone moiety. LHVS is a useful tool for studyting CatS-mediated responses in cultures (typical dosing ranges: 25 nM to 10μM) and in animals in vivoincluding CatS-induced itch in mice (30 mg/kg sc.)morphine-induced antinociceptive tolerance in rats (50 nmol/r at itrathetically) and mechanical hyperalgesia in nerve-injured rats (3-30 mg/kg sc.). | [in vivo]
LHVS (3-30 mg/kg, SC, once) shows anti-hyperalgesic effect in neuropathic rats[4].
LHVS (30 nmol per rat, spinal delivery, daily) is antinociceptive in neuropathic rats[5].
LHVS (1-50 nmol per rat, Intrathecal injection, daily) reverses established neuropathic mechanical hyperalgesia in 14-day neuropathic rats[5]. | Animal Model: | Male Wistar rats (180-220 g)[4] | | Dosage: | 3-30 mg/kg | | Administration: | SC, once | | Result: | Produced a dose-dependent reversal of the mechanical hyperalgesia which lasted up to 3 h in neuropathic rats. In contrast, a single systemic administration of LHVS did not reverse mechanical allodynia in neuropathic rats. |
| Animal Model: | Male Wistar rats received a partial ligation of the left sciatic nerve (PNL)[5] | | Dosage: | 30 nmol per rat | | Administration: | Spinal delivery, Daily | | Result: | Failed to prevent the development of allodynia when continuous delivery from day 0 to day 7 post-PNL, but significantly reversed allodynia on day 7 post-PNL. In addition, the delivery of LHVS from day 7 to day 14 post-PNL significantly reversed established mechanical allodynia from day 8. |
| Animal Model: | Male Wistar rats received a partial ligation of the left sciatic nerve (PNL)[5] | | Dosage: | 1, 10 or 50 nmol per rat | | Administration: | Intrathecal injection, Daily | | Result: | Reduced established mechanical hyperalgesia. This effect was dose-dependent and remained significant until 3 h after administration of the highest dose. |
| [IC 50]
cathepsin S; cathepsin K; cathepsin L; Cathepsin B | [storage]
Store at -20°C | [References]
[1] Wilson SR, 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. DOI:10.1074/jbc.M805280200
[2] Teo CF, et al.Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion. Antimicrob Agents Chemother. 2007 Feb;51(2):679-88. DOI:10.1128/AAC.01059-06
[3] Riese RJ, 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. DOI:10.1016/s1074-7613(00)80249-6
[4] Barclay J, et al. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain. 2007 Aug;130(3):225-234. DOI:10.1016/j.pain.2006.11.017
[5] Clark AK, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10655-60. DOI:10.1073/pnas.0610811104 |
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