L-006235 | CAS#294623-49-7 | cathespin K inhibitor |

MedKoo Cat#: 510222 | Name: L006235

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

L006235

CAS#294623-49-7

Theoretical Analysis

MedKoo Cat#: 510222

Name: L006235

CAS#: 294623-49-7

Chemical Formula: C24H30N6O2S

Exact Mass: 466.2151

Molecular Weight: 466.60

Elemental Analysis: C, 61.78; H, 6.48; N, 18.01; O, 6.86; S, 6.87

Price and Availability

Size	Price	Availability
25mg	USD 250.00	2 Weeks
50mg	USD 450.00	2 Weeks
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,750.00	2 Weeks
2g	USD 6,250.00	2 Weeks

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Related CAS #

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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

More Info

Product Data

Product Data

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMF	15.0	32.15
	DMSO	31.0	66.37
	DMSO:PBS (pH 7.2) (1:1)	0.5	1.07

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 466.60 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: 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.