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LHVS (K110717) is a novel, potent, non-selective and irreversible cysteine protease cathepsin S (CatS) inhibitor. LHVS effectively blocks T. gondii microneme protein secretion (IC50=10 μM), gliding motility, and cell invasion.
Physicochemical Properties
| Molecular Formula | C28H37N3O5S |
| Molecular Weight | 527.675486326218 |
| Exact Mass | 527.245 |
| CAS # | 170111-28-1 |
| PubChem CID | 5287864 |
| Appearance | White to off-white solid powder |
| LogP | 3.7 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 11 |
| Heavy Atom Count | 37 |
| Complexity | 836 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | [C@@H](CC(C)C)(NC(N1CCOCC1)=O)C(=O)N[C@@H](CCC1C=CC=CC=1)/C=C/S(C1C=CC=CC=1)(=O)=O |
| InChi Key | YUMYYTORLYHUFW-ZUDLOMHPSA-N |
| InChi Code | InChI=1S/C28H37N3O5S/c1-22(2)21-26(30-28(33)31-16-18-36-19-17-31)27(32)29-24(14-13-23-9-5-3-6-10-23)15-20-37(34,35)25-11-7-4-8-12-25/h3-12,15,20,22,24,26H,13-14,16-19,21H2,1-2H3,(H,29,32)(H,30,33)/b20-15+/t24-,26-/m1/s1 |
| Chemical Name | N-[(2R)-1-[[(E,3R)-1-(Benzenesulfonyl)-5-phenylpent-1-en-3-yl]amino]-4-methyl-1-oxopentan-2-yl]morpholine-4-carboxamide |
| Synonyms | K-110717 K 110717 K110717 |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | When compared to untreated osteoclasts, LHVS (5 μM, 2 hours) caused a 50% decrease in actin ring formation in wild-type osteoclasts [1]. LHVS inhibits cathepsins K, L, S, and B at 5 μM and acts on osteoclasts in a dose-dependent manner [1]. In HOM2 cells, LHVS (1–5 nM) selectively inhibits cathepsin S, maintaining the functional activity of other cysteine proteases [3]. By stopping micronemes from releasing at least two essential invasion proteins, MIC2 and M2AP, LHVS hinders tachyzoite attachment [2]. LHVS (50 μM) specifically reduces the secretion of microsomal proteins [2]. |
| ln Vivo | In neuropathic rats, LHVS (3–30 mg/kg, subcutaneous injection, once) exhibits anti-hyperalgesic effects [4]. Neuropathic rats show analgesic effects from daily spinal administration of 30 nmol per rat of LHVS [5]. In 14-day-old neuropathic rats, LHVS (1-50 nmol per rat, intrathecally, daily) reverses established neuropathic mechanical hyperalgesia [5]. |
| Animal Protocol |
Animal/Disease Models: Male Wistar rat (180-220 g) [4] Doses: 3-30 mg/kg Route of Administration: subcutaneous injection, once Experimental Results:Produces dose-dependent reversal of mechanical hyperalgesia, long-lasting in neuropathic rats up to 3 hrs (hrs (hours)). In contrast, a single systemic administration of LHVS did not reverse mechanical allodynia in neuropathic rats. Animal/Disease Models: Male Wistar rats received partial ligation of the left sciatic nerve (PNL) [5] Doses: 30 nmol per rat Route of Administration: spinal cord, daily Experimental Results: continuous administration from day 0 to day 1 failed to prevent the occurrence of allodynia on day 7 after PNL, but Dramatically reversed allodynia on day 7 after PNL. Furthermore, LHVS from days 7 to 14 after PNL Dramatically reversed established mechanical allodynia from day 8 onwards. Animal/Disease Models: Male Wistar rats underwent partial ligation of the left sciatic nerve (PNL) [5] Doses: 1. 10 or 50 nmol per rat Route of Administration: Intrathecal injection, daily Experimental Results: Reduction of established mechani |
| References |
[1]. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J Biol Chem. 2009 Jan 23;284(4):2584-92. [2]. Cysteine protease inhibitors block Toxoplasma gondii microneme secretion and cell invasion. Antimicrob Agents Chemother. 2007 Feb;51(2):679-88. [3]. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Immunity. 1996 Apr;4(4):357-66. [4]. Role of the cysteine protease cathepsin S in neuropathic hyperalgesia. Pain. 2007 Aug;130(3):225-234. [5]. 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. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~189.51 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.74 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8951 mL | 9.4754 mL | 18.9509 mL | |
| 5 mM | 0.3790 mL | 1.8951 mL | 3.7902 mL | |
| 10 mM | 0.1895 mL | 0.9475 mL | 1.8951 mL |