CA-074 methyl ester | CAS#147859-80-1 | cathepsin B inhibitor

MedKoo Cat#: 561713 | Name: CA-074 methyl ester

Description:

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

CA-074 methyl ester is a selective and cell-permeable inhibitor of cathepsin B.

Chemical Structure

CA-074 methyl ester

CAS#147859-80-1

Theoretical Analysis

MedKoo Cat#: 561713

Name: CA-074 methyl ester

CAS#: 147859-80-1

Chemical Formula: C19H30N2O6

Exact Mass: 382.2104

Molecular Weight: 382.45

Elemental Analysis: C, 59.67; H, 7.91; N, 7.32; O, 25.10

Price and Availability

Size	Price	Availability
50mg	USD 950.00	2 Weeks
100mg	USD 1,650.00	2 Weeks
200mg	USD 2,650.00	2 Weeks
500mg	USD 4,650.00	2 Weeks
1g	USD 7,450.00	2 Weeks

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Synonym

Ca-074Me; Ca-074Me; Ca-074Me; CA-074 methyl ester; CA 074 methyl ester; CA074 methyl ester

IUPAC/Chemical Name

methyl ((2S,3S)-3-butyryloxirane-2-carbonyl)-L-isoleucyl-L-prolinate

InChi Key

VYTVGOLUTMTRTE-AMSCCUFHSA-N

InChi Code

InChI=1S/C19H30N2O6/c1-5-8-13(22)15-16(27-15)17(23)20-14(11(3)6-2)18(24)21-10-7-9-12(21)19(25)26-4/h11-12,14-16H,5-10H2,1-4H3,(H,20,23)/t11-,12-,14-,15+,16-/m0/s1

SMILES Code

O=C(OC)[C@H]1N(C([C@H]([C@@H](C)CC)NC([C@H]2O[C@@H]2C(CCC)=O)=O)=O)CCC1

Appearance

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

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:

CA-074 methyl ester (CA-074 Me, Cathepsin B Inhibitor IV) is a membrane-permeable derivative of CA-074 and acts as an irreversible cathepsin B inhibitor.

In vitro activity:

In order to determine the critical timing of CA-074Me inhibition, osteoclastogenesis was induced through RANKL and CA-074Me was added at various time points after stimulation in vitro. It is interesting to note that CA-074Me maintains its anti-osteoclastogenic effect up to 24 h post-RANKL stimulation. This effect is possibly due to interference of an early cell signaling pathway. CA-074Me completely blocked osteoclast formation if administered within 12 h of RANKL stimulation. Even at the 24 h time point, the quantity of osteoclasts is still significantly reduced and the multinucleated morphology is altered (Fig. 4A and B). This experiment clearly shows that CA-074Me exerts it effect within 24 h after RANKL-stimulation of BMMs. Reference: J Orthop Res. 2015 Oct;33(10):1474-86. https://doi.org/10.1002/jor.22795

In vivo activity:

The marked elevation in serum aminotransferase activity and prothrombin time found in LPS/D-GalN-treated mice was significantly improved by pretreatment with CA-074me. The efficacy of CA-074me was also confirmed by histological analysis and TUNEL assay. The survival rate significantly improved in LPS/D-GalN-induced mice given CA-074me compared with untreated mice. LPS/D-GalN-induced caspase-3 and caspase-9 activation was remarkably suppressed by CA-074me. However, the increased levels of serum TNF-alpha and elevated caspase-8 activity in AHF mice were not significantly reduced by CA-074me. Moreover, CA-074me sharply reduced the increased expression of cytosolic cytochrome c and markedly augmented Bcl-2 expression. Reference: Hepatobiliary Pancreat Dis Int. 2013 Feb;12(1):80-6. https://linkinghub.elsevier.com/retrieve/pii/S1499-3872(13)60010-7

	Solvent	mg/mL	mM
Solubility
	DMSO	200.0	522.94

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 382.45 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:

In vitro protocol:

1. Patel N, Nizami S, Song L, Mikami M, Hsu A, Hickernell T, Chandhanayingyong C, Rho S, Compton JT, Caldwell JM, Kaiser PB, Bai H, Lee HG, Fischer CR, Lee FY. CA-074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c-FOS signaling pathways. J Orthop Res. 2015 Oct;33(10):1474-86. doi: 10.1002/jor.22795. Epub 2015 Aug 20. PMID: 25428830. 2. Cho K, Yoon SY, Choi JE, Kang HJ, Jang HY, Kim DH. CA-074Me, a cathepsin B inhibitor, decreases APP accumulation and protects primary rat cortical neurons treated with okadaic acid. Neurosci Lett. 2013 Aug 26;548:222-7. doi: 10.1016/j.neulet.2013.05.056. Epub 2013 Jun 5. PMID: 23748042.

In vivo protocol:

1. Yan BZ, Chen LY, Kang L, Wang XR, Bi MR, Wang W, Yang BS. Hepatoprotective effects of cathepsin B inhibitor on acute hepatic failure induced by lipopolysaccharide/D-galactosamine in mice. Hepatobiliary Pancreat Dis Int. 2013 Feb;12(1):80-6. doi: 10.1016/s1499-3872(13)60010-7. PMID: 23392803. 2. Zhang L, Fu XH, Yu Y, Shui RH, Li C, Zeng HY, Qiao YL, Ni LY, Wang Q. Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis. Lab Invest. 2015 Jan;95(1):65-77. doi: 10.1038/labinvest.2014.135. Epub 2014 Nov 10. PMID: 25384123.

1: Yang Q, Zhang C, Wei H, Meng Z, Li G, Xu Y, Chen Y. Caspase-Independent Pathway is Related to Nilotinib Cytotoxicity in Cultured Cardiomyocytes. Cell Physiol Biochem. 2017;42(6):2182-2193. doi: 10.1159/000479993. Epub 2017 Aug 15. PubMed PMID: 28813698. 2: Wu Z, Ni J, Liu Y, Teeling JL, Takayama F, Collcutt A, Ibbett P, Nakanishi H. Cathepsin B plays a critical role in inducing Alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice. Brain Behav Immun. 2017 Oct;65:350-361. doi: 10.1016/j.bbi.2017.06.002. Epub 2017 Jun 10. PubMed PMID: 28610747. 3: Zhu YM, Gao X, Ni Y, Li W, Kent TA, Qiao SG, Wang C, Xu XX, Zhang HL. Sevoflurane postconditioning attenuates reactive astrogliosis and glial scar formation after ischemia-reperfusion brain injury. Neuroscience. 2017 Jul 25;356:125-141. doi: 10.1016/j.neuroscience.2017.05.004. Epub 2017 May 10. PubMed PMID: 28501505. 4: Wang L, Chen Y, Li X, Zhang Y, Gulbins E, Zhang Y. Enhancement of endothelial permeability by free fatty acid through lysosomal cathepsin B-mediated Nlrp3 inflammasome activation. Oncotarget. 2016 Nov 8;7(45):73229-73241. doi: 10.18632/oncotarget.12302. PubMed PMID: 27689324; PubMed Central PMCID: PMC5341975. 5: Li X, Wu Z, Ni J, Liu Y, Meng J, Yu W, Nakanishi H, Zhou Y. Cathepsin B Regulates Collagen Expression by Fibroblasts via Prolonging TLR2/NF-κB Activation. Oxid Med Cell Longev. 2016;2016:7894247. doi: 10.1155/2016/7894247. Epub 2016 Aug 28. PubMed PMID: 27648120; PubMed Central PMCID: PMC5018341. 6: Zuo X, Hou Q, Jin J, Zhan L, Li X, Sun W, Lin K, Xu E. Inhibition of Cathepsin B Alleviates Secondary Degeneration in Ipsilateral Thalamus After Focal Cerebral Infarction in Adult Rats. J Neuropathol Exp Neurol. 2016 Sep;75(9):816-26. doi: 10.1093/jnen/nlw054. Epub 2016 Jun 30. PubMed PMID: 27371711. 7: Fox C, Cocchiaro P, Oakley F, Howarth R, Callaghan K, Leslie J, Luli S, Wood KM, Genovese F, Sheerin NS, Moles A. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease. Sci Rep. 2016 Feb 2;6:20101. doi: 10.1038/srep20101. PubMed PMID: 26831567; PubMed Central PMCID: PMC4735715. 8: Xu Y, Wang J, Song X, Wei R, He F, Peng G, Luo B. Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats. Brain Res Bull. 2016 Jan;120:97-105. doi: 10.1016/j.brainresbull.2015.11.007. Epub 2015 Nov 10. PubMed PMID: 26562519. 9: Ni J, Wu Z, Peterts C, Yamamoto K, Qing H, Nakanishi H. The Critical Role of Proteolytic Relay through Cathepsins B and E in the Phenotypic Change of Microglia/Macrophage. J Neurosci. 2015 Sep 9;35(36):12488-501. doi: 10.1523/JNEUROSCI.1599-15.2015. PubMed PMID: 26354916. 10: Gicquel T, Robert S, Loyer P, Victoni T, Bodin A, Ribault C, Gleonnec F, Couillin I, Boichot E, Lagente V. IL-1β production is dependent on the activation of purinergic receptors and NLRP3 pathway in human macrophages. FASEB J. 2015 Oct;29(10):4162-73. doi: 10.1096/fj.14-267393. Epub 2015 Jun 26. PubMed PMID: 26116704. 11: Wang Z, Cheng X, Meng Q, Wang P, Shu B, Hu Q, Hu M, Zhong G. Azadirachtin-induced apoptosis involves lysosomal membrane permeabilization and cathepsin L release in Spodoptera frugiperda Sf9 cells. Int J Biochem Cell Biol. 2015 Jul;64:126-35. doi: 10.1016/j.biocel.2015.03.018. Epub 2015 Apr 4. PubMed PMID: 25849458. 12: Brojatsch J, Lima H Jr, Palliser D, Jacobson LS, Muehlbauer SM, Furtado R, Goldman DL, Lisanti MP, Chandran K. Distinct cathepsins control necrotic cell death mediated by pyroptosis inducers and lysosome-destabilizing agents. Cell Cycle. 2015;14(7):964-72. doi: 10.4161/15384101.2014.991194. PubMed PMID: 25830414; PubMed Central PMCID: PMC4614982. 13: Bian B, Mongrain S, Cagnol S, Langlois MJ, Boulanger J, Bernatchez G, Carrier JC, Boudreau F, Rivard N. Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis. Mol Carcinog. 2016 May;55(5):671-87. doi: 10.1002/mc.22312. Epub 2015 Mar 25. PubMed PMID: 25808857; PubMed Central PMCID: PMC4832390. 14: Moriwaki K, Bertin J, Gough PJ, Orlowski GM, Chan FK. Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death. Cell Death Dis. 2015 Feb 12;6:e1636. doi: 10.1038/cddis.2015.16. PubMed PMID: 25675296; PubMed Central PMCID: PMC4669795. 15: Steverding D. Evaluation of trypanocidal activity of combinations of anti-sleeping sickness drugs with cysteine protease inhibitors. Exp Parasitol. 2015 Apr-May;151-152:28-33. doi: 10.1016/j.exppara.2015.01.016. Epub 2015 Feb 4. PubMed PMID: 25662707. 16: Patel N, Nizami S, Song L, Mikami M, Hsu A, Hickernell T, Chandhanayingyong C, Rho S, Compton JT, Caldwell JM, Kaiser PB, Bai H, Lee HG, Fischer CR, Lee FY. CA-074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c-FOS signaling pathways. J Orthop Res. 2015 Oct;33(10):1474-86. doi: 10.1002/jor.22795. Epub 2015 Aug 20. PubMed PMID: 25428830. 17: Zhang L, Fu XH, Yu Y, Shui RH, Li C, Zeng HY, Qiao YL, Ni LY, Wang Q. Treatment with CA-074Me, a Cathepsin B inhibitor, reduces lung interstitial inflammation and fibrosis in a rat model of polymyositis. Lab Invest. 2015 Jan;95(1):65-77. doi: 10.1038/labinvest.2014.135. Epub 2014 Nov 10. PubMed PMID: 25384123. 18: Hussain S, Sangtian S, Anderson SM, Snyder RJ, Marshburn JD, Rice AB, Bonner JC, Garantziotis S. Inflammasome activation in airway epithelial cells after multi-walled carbon nanotube exposure mediates a profibrotic response in lung fibroblasts. Part Fibre Toxicol. 2014 Jun 10;11:28. doi: 10.1186/1743-8977-11-28. PubMed PMID: 24915862; PubMed Central PMCID: PMC4067690. 19: Tong B, Wan B, Wei Z, Wang T, Zhao P, Dou Y, Lv Z, Xia Y, Dai Y. Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis. Clin Exp Immunol. 2014 Sep;177(3):586-97. doi: 10.1111/cei.12357. PubMed PMID: 24749816; PubMed Central PMCID: PMC4137842. 20: Fischer S, Ronellenfitsch MW, Thiepold AL, Harter PN, Reichert S, Kögel D, Paschke R, Mittelbronn M, Weller M, Steinbach JP, Fulda S, Bähr O. Hypoxia enhances the antiglioma cytotoxicity of B10, a glycosylated derivative of betulinic acid. PLoS One. 2014 Apr 17;9(4):e94921. doi: 10.1371/journal.pone.0094921. eCollection 2014. PubMed PMID: 24743710; PubMed Central PMCID: PMC3990545.