WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 510222
CAS#: 294623-49-7
Description: L006235, also called L235, is a potent, reversible cathepsin K inhibitor (IC50 = 0.25 nM) that displays > 4000-fold selectivity over cathepsins B, L and S.
MedKoo Cat#: 510222
Name: L006235
CAS#: 294623-49-7
Chemical Formula: C24H30N6O2S
Exact Mass: 466.2151
Molecular Weight: 466.604
Elemental Analysis: C, 61.78; H, 6.48; N, 18.01; O, 6.86; S, 6.87
Synonym: L006235; L 006235; L-006235; L235; L-235; L 235;
IUPAC/Chemical Name: N-(1-((cyanomethyl)carbamoyl)cyclohexyl)-4-(2-(4-methylpiperazin-1-yl)thiazol-4-yl)benzamide
InChi Key: FIVYCSWOCXEWSE-UHFFFAOYSA-N
InChi Code: InChI=1S/C24H30N6O2S/c1-29-13-15-30(16-14-29)23-27-20(17-33-23)18-5-7-19(8-6-18)21(31)28-24(9-3-2-4-10-24)22(32)26-12-11-25/h5-8,17H,2-4,9-10,12-16H2,1H3,(H,26,32)(H,28,31)
SMILES Code: O=C(NC1(C(NCC#N)=O)CCCCC1)C2=CC=C(C3=CSC(N4CCN(C)CC4)=N3)C=C2
Appearance: Solid powder
Purity: >98%
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >5 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | L-006235 (L-235) is a potent, selective, reversible and orally active inhibitor of cathepsin K, with an IC50 of 5 nM in bone resorption assay. |
| In vitro activity: | TBD |
| In vivo activity: | Preventative L-006235 inhibited weight-bearing asymmetry from day 14, with this measure nearly abolished by the higher dose. In the same treatment setting, L-006235 prevented lowering of hind paw withdrawal thresholds from day 7. Exposure to L-006235 in plasma was higher for the 100 mg/kg dose, compared with 30 mg/kg. Therapeutic dosing with L-006235 from day 14 significantly inhibited weight-bearing asymmetry, compared with monosodium iodoacetate vehicle rats. Reference: Pain Rep. 2018 Oct 5;3(6):e685. https://pubmed.ncbi.nlm.nih.gov/30706033/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 15.0 | 32.15 | |
| DMSO | 30.97 | 66.37 | |
| DMSO:PBS (pH 7.2) (1:1) | 0.5 | 1.07 |
The following data is based on the product molecular weight 466.604 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Nwosu LN, Gowler PRW, Burston JJ, Rizoska B, Tunblad K, Lindström E, Grabowska U, Li L, McWilliams DF, Walsh DA, Chapman V. Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain Rep. 2018 Oct 5;3(6):e685. doi: 10.1097/PR9.0000000000000685. PMID: 30706033; PMCID: PMC6344135. 2. Pennypacker BL, Duong LT, Cusick TE, Masarachia PJ, Gentile MA, Gauthier JY, Black WC, Scott BB, Samadfam R, Smith SY, Kimmel DB. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011 Feb;26(2):252-62. doi: 10.1002/jbmr.223. PMID: 20734451. |
| In vitro protocol: | TBD |
| In vivo protocol: | 1. Nwosu LN, Gowler PRW, Burston JJ, Rizoska B, Tunblad K, Lindström E, Grabowska U, Li L, McWilliams DF, Walsh DA, Chapman V. Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain Rep. 2018 Oct 5;3(6):e685. doi: 10.1097/PR9.0000000000000685. PMID: 30706033; PMCID: PMC6344135. 2. Pennypacker BL, Duong LT, Cusick TE, Masarachia PJ, Gentile MA, Gauthier JY, Black WC, Scott BB, Samadfam R, Smith SY, Kimmel DB. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011 Feb;26(2):252-62. doi: 10.1002/jbmr.223. PMID: 20734451. |
1: Nwosu LN, Gowler PRW, Burston JJ, Rizoska B, Tunblad K, Lindström E, Grabowska U, Li L, McWilliams DF, Walsh DA, Chapman V. Analgesic effects of the cathepsin K inhibitor L-006235 in the monosodium iodoacetate model of osteoarthritis pain. Pain Rep. 2018 Oct 5;3(6):e685. doi: 10.1097/PR9.0000000000000685. PMID: 30706033; PMCID: PMC6344135.
2: Yu NY, Fathi A, Murphy CM, Mikulec K, Peacock L, Cantrill LC, Dehghani F, Little DG, Schindeler A. Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l-lactide-co-glycolide) nanospheres. J Biomed Mater Res B Appl Biomater. 2017 Jan;105(1):136-144. doi: 10.1002/jbm.b.33481. Epub 2015 Oct 5. PMID: 26435360.
3: Pennypacker BL, Oballa RM, Levesque S, Kimmel DB, Duong LT. Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly growing rabbits. BMC Musculoskelet Disord. 2013 Dec 9;14:344. doi: 10.1186/1471-2474-14-344. PMID: 24321244; PMCID: PMC3878918.
4: Soung do Y, Gentile MA, Duong LT, Drissi H. Effects of pharmacological inhibition of cathepsin K on fracture repair in mice. Bone. 2013 Jul;55(1):248-55. doi: 10.1016/j.bone.2013.02.010. Epub 2013 Feb 26. PMID: 23486186.
5: Hayami T, Zhuo Y, Wesolowski GA, Pickarski M, Duong LT. Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone. 2012 Jun;50(6):1250-9. doi: 10.1016/j.bone.2012.03.025. Epub 2012 Mar 30. PMID: 22484689.
6: Pennypacker BL, Duong LT, Cusick TE, Masarachia PJ, Gentile MA, Gauthier JY, Black WC, Scott BB, Samadfam R, Smith SY, Kimmel DB. Cathepsin K inhibitors prevent bone loss in estrogen-deficient rabbits. J Bone Miner Res. 2011 Feb;26(2):252-62. doi: 10.1002/jbmr.223. PMID: 20734451.
7: Svelander L, Erlandsson-Harris H, Astner L, Grabowska U, Klareskog L, Lindstrom E, Hewitt E. Inhibition of cathepsin K reduces bone erosion, cartilage degradation and inflammation evoked by collagen-induced arthritis in mice. Eur J Pharmacol. 2009 Jun 24;613(1-3):155-62. doi: 10.1016/j.ejphar.2009.03.074. Epub 2009 Apr 7. PMID: 19358841.
8: Le Gall C, Bonnelye E, Clézardin P. Cathepsin K inhibitors as treatment of bone metastasis. Curr Opin Support Palliat Care. 2008 Sep;2(3):218-22. doi: 10.1097/SPC.0b013e32830baea9. PMID: 18685424.
9: Desmarais S, Black WC, Oballa R, Lamontagne S, Riendeau D, Tawa P, Duong LT, Pickarski M, Percival MD. Effect of cathepsin k inhibitor basicity on in vivo off-target activities. Mol Pharmacol. 2008 Jan;73(1):147-56. doi: 10.1124/mol.107.039511. Epub 2007 Oct 16. PMID: 17940194.
10: Black WC, Percival MD. The consequences of lysosomotropism on the design of selective cathepsin K inhibitors. Chembiochem. 2006 Oct;7(10):1525-35. doi: 10.1002/cbic.200600149. PMID: 16921579.
11: Falgueyret JP, Desmarais S, Oballa R, Black WC, Cromlish W, Khougaz K, Lamontagne S, Massé F, Riendeau D, Toulmond S, Percival MD. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J Med Chem. 2005 Dec 1;48(24):7535-43. doi: 10.1021/jm0504961. PMID: 16302795.
12: Palmer JT, Bryant C, Wang DX, Davis DE, Setti EL, Rydzewski RM, Venkatraman S, Tian ZQ, Burrill LC, Mendonca RV, Springman E, McCarter J, Chung T, Cheung H, Janc JW, McGrath M, Somoza JR, Enriquez P, Yu ZW, Strickley RM, Liu L, Venuti MC, Percival MD, Falgueyret JP, Prasit P, Oballa R, Riendeau D, Young RN, Wesolowski G, Rodan SB, Johnson C, Kimmel DB, Rodan G. Design and synthesis of tri-ring P3 benzamide-containing aminonitriles as potent, selective, orally effective inhibitors of cathepsin K. J Med Chem. 2005 Dec 1;48(24):7520-34. doi: 10.1021/jm058198r. PMID: 16302794.
