Balicatib | AAE581 | CAS#354813-19-7 | Cathepsin K inhibitor

MedKoo Cat#: 510221 | Name: Balicatib

Description:

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

Balicatib, also known as AAE581, is an inhibitor of the osteoclastic enzyme cathepsin K. Balicatib partially prevented ovariectomy-induced changes in bone mass, inhibited bone turnover at most sites, and had an unexpected stimulatory effect on periosteal bone formation.

Chemical Structure

Balicatib

CAS#354813-19-7

Theoretical Analysis

MedKoo Cat#: 510221

Name: Balicatib

CAS#: 354813-19-7

Chemical Formula: C23H33N5O2

Exact Mass: 411.2634

Molecular Weight: 411.54

Elemental Analysis: C, 67.12; H, 8.08; N, 17.02; O, 7.78

Price and Availability

Size	Price	Availability
100mg	USD 950.00	2 Weeks
200mg	USD 1,650.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 3,250.00	2 Weeks
2g	USD 4,950.00	2 Weeks
5g	USD 8,250.00	2 Weeks

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Synonym

Balicatib; AAE581; AAE-581; AAE 581

IUPAC/Chemical Name

N-(1-((cyanomethyl)carbamoyl)cyclohexyl)-4-(4-propylpiperazin-1-yl)benzamide

InChi Key

LLCRBOWRJOUJAE-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H33N5O2/c1-2-14-27-15-17-28(18-16-27)20-8-6-19(7-9-20)21(29)26-23(10-4-3-5-11-23)22(30)25-13-12-24/h6-9H,2-5,10-11,13-18H2,1H3,(H,25,30)(H,26,29)

SMILES Code

O=C(NC1(C(NCC#N)=O)CCCCC1)C2=CC=C(N3CCN(CCC)CC3)C=C2

Appearance

white to off-white solid powder

Purity

>98% (or refer to the Certificate of Analysis)

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

>2 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:

Balicatib (AAE-581) is an inhibitor of cathepsin K.

In vitro activity:

TBD

In vivo activity:

The efficacy of balicatib (AAE581), a novel inhibitor of human cathepsin K, on bone mass and dynamic histomorphometric endpoints was tested in ovariectomized monkeys. Eighty adult female Macaca fascicularis underwent bilateral ovariectomies and were dosed twice daily by oral gavage with balicatib at 0, 3, 10, and 50 mg/kg for 18 months (groups O, L, M, H, respectively). In both spine and femur, group O animals lost BMD and all other groups gained BMD between 0 and 18 months. In balicatib-treated animals, BMD change in the spine was intermediate between group S and O, with groups L and M significantly different from group O. In femur, all three doses of balicatib significantly increased BMD gain relative to group O and group mean values were also higher than group S. Most histomorphometric indices of bone turnover in vertebra and femoral neck were significantly lower than group O with balicatib treatment, except that periosteal bone formation rates (Ps.BFR) were significantly higher. Ps.BFR in mid-femur was also significantly increased by treatment. Overall, balicatib partially prevented ovariectomy-induced changes in bone mass, inhibited bone turnover at most sites, and had an unexpected stimulatory effect on periosteal bone formation. Reference: Osteoporos Int. 2012 Jan;23(1):339-49. https://link.springer.com/article/10.1007%2Fs00198-011-1593-2

	Solvent	mg/mL	mM
Solubility
	DMSO	52.0	126.45
	DMF	25.0	60.75
	DMF:PBS (pH 7.2) (1:1)	0.5	1.21
	Ethanol	1.8	4.25

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 411.54 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. Jerome C, Missbach M, Gamse R. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int. 2012 Jan;23(1):339-49. doi: 10.1007/s00198-011-1593-2. Epub 2011 Mar 5. PMID: 21380636.

In vitro protocol:

TBD

In vivo protocol:

1: Jerome C, Missbach M, Gamse R. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int. 2012 Jan;23(1):339-49. doi: 10.1007/s00198-011-1593-2. Epub 2011 Mar 5. PMID: 21380636. 2: Jerome C, Missbach M, Gamse R. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos Int. 2011 Dec;22(12):3001-11. doi: 10.1007/s00198-011-1529-x. Epub 2011 Feb 10. PMID: 21308366. 3: Peroni A, Zini A, Braga V, Colato C, Adami S, Girolomoni G. Drug-induced morphea: report of a case induced by balicatib and review of the literature. J Am Acad Dermatol. 2008 Jul;59(1):125-9. doi: 10.1016/j.jaad.2008.03.009. Epub 2008 Apr 14. PMID: 18410981. 4: Rünger TM, Adami S, Benhamou CL, Czerwiński E, Farrerons J, Kendler DL, Mindeholm L, Realdi G, Roux C, Smith V. Morphea-like skin reactions in patients treated with the cathepsin K inhibitor balicatib. J Am Acad Dermatol. 2012 Mar;66(3):e89-96. doi: 10.1016/j.jaad.2010.11.033. Epub 2011 May 14. PMID: 21571394. 5: Rocho FR, Bonatto V, Lameiro RF, Lameira J, Leitão A, Montanari CA. A patent review on cathepsin K inhibitors to treat osteoporosis (2011 - 2021). Expert Opin Ther Pat. 2022 May;32(5):561-573. doi: 10.1080/13543776.2022.2040480. Epub 2022 Mar 10. PMID: 35137661. 6: Gamsjäger M, Resch H. Cathepsin K-Inhibitoren: präklinische und klinische Daten [Cathepsin K antagonists: preclinical and clinical data]. Wien Med Wochenschr. 2015 Feb;165(3-4):65-70. German. doi: 10.1007/s10354-014-0336-3. Epub 2015 Jan 9. PMID: 25572547. 7: Soundararajan A, Ghag SA, Vuda SS, Wang T, Pattabiraman PP. Cathepsin K Regulates Intraocular Pressure by Modulating Extracellular Matrix Remodeling and Actin-Bundling in the Trabecular Meshwork Outflow Pathway. Cells. 2021 Oct 24;10(11):2864. doi: 10.3390/cells10112864. PMID: 34831087; PMCID: PMC8616380. 8: Stone JA, McCrea JB, Witter R, Zajic S, Stoch SA. Clinical and translational pharmacology of the cathepsin K inhibitor odanacatib studied for osteoporosis. Br J Clin Pharmacol. 2019 Jun;85(6):1072-1083. doi: 10.1111/bcp.13869. Epub 2019 Mar 18. PMID: 30663085; PMCID: PMC6533439. 9: Duong le T, Leung AT, Langdahl B. Cathepsin K Inhibition: A New Mechanism for the Treatment of Osteoporosis. Calcif Tissue Int. 2016 Apr;98(4):381-97. doi: 10.1007/s00223-015-0051-0. Epub 2015 Sep 3. PMID: 26335104. 10: Vashum Y, Premsingh R, Kottaiswamy A, Soma M, Padmanaban A, Kalaiselvan P, Samuel S. Inhibitory effect of cathepsin K inhibitor (ODN-MK-0822) on invasion, migration and adhesion of human breast cancer cells in vitro. Mol Biol Rep. 2021 Jan;48(1):105-116. doi: 10.1007/s11033-020-05951-0. Epub 2020 Dec 8. PMID: 33294960. 11: Desmarais S, Massé F, Percival MD. Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol Chem. 2009 Sep;390(9):941-8. doi: 10.1515/BC.2009.092. PMID: 19453281. 12: Law S, Andrault PM, Aguda AH, Nguyen NT, Kruglyak N, Brayer GD, Brömme D. Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib. Biochem J. 2017 Feb 20;474(5):851-864. doi: 10.1042/BCJ20160985. PMID: 28049758. 13: Vasiljeva O, Reinheckel T, Peters C, Turk D, Turk V, Turk B. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr Pharm Des. 2007;13(4):387-403. doi: 10.2174/138161207780162962. PMID: 17311556. 14: 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. 15: 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. 16: 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. 17: Gauthier JY, Chauret N, Cromlish W, Desmarais S, Duong LT, Falgueyret JP, Kimmel DB, Lamontagne S, Léger S, LeRiche T, Li CS, Massé F, McKay DJ, Nicoll- Griffith DA, Oballa RM, Palmer JT, Percival MD, Riendeau D, Robichaud J, Rodan GA, Rodan SB, Seto C, Thérien M, Truong VL, Venuti MC, Wesolowski G, Young RN, Zamboni R, Black WC. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg Med Chem Lett. 2008 Feb 1;18(3):923-8. doi: 10.1016/j.bmcl.2007.12.047. Epub 2008 Jan 15. PMID: 18226527. 18: Chappard D, Libouban H, Mindeholm L, Baslé MF, Legrand E, Audran M. The cathepsin K inhibitor AAE581 induces morphological changes in osteoclasts of treated patients. Microsc Res Tech. 2010 Jul;73(7):726-32. doi: 10.1002/jemt.20813. PMID: 20025055.