SJA6017 | CAS#190274-53-4 | Calpain Inhibitor

MedKoo Cat#: 555125 | Name: SJA6017

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Description:

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

SJA6017, also known as Calpain Inhibitor VI, is a calpain inhibitor. Treatment with SJA6017 reduces apoptotic cell death, preserves spinal cord tissue and improves functional outcome. Treating calpain-induced apoptosis with this agent may be a feasible therapeutic strategy for patients with spinal cord injury.

Chemical Structure

SJA6017

CAS#190274-53-4

Theoretical Analysis

MedKoo Cat#: 555125

Name: SJA6017

CAS#: 190274-53-4

Chemical Formula: C17H25FN2O4S

Exact Mass: 372.1519

Molecular Weight: 372.46

Elemental Analysis: C, 54.82; H, 6.77; F, 5.10; N, 7.52; O, 17.18; S, 8.61

Price and Availability

Size	Price	Availability	Quantity
1mg	USD 400.00	2 weeks

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Synonym

Calpain Inhibitor VI; Calpain Inhibitor 4; Calpain-In-4; SJA6017; SJA-6017; SJA 6017.

IUPAC/Chemical Name

(S)-2-((4-fluorophenyl)sulfonamido)-3-methyl-N-((S)-4-methyl-1-oxopentan-2-yl)butanamide

InChi Key

WSJWUIDLGZAXID-HOCLYGCPSA-N

InChi Code

InChI=1S/C17H25FN2O4S/c1-11(2)9-14(10-21)19-17(22)16(12(3)4)20-25(23,24)15-7-5-13(18)6-8-15/h5-8,10-12,14,16,20H,9H2,1-4H3,(H,19,22)/t14-,16-/m0/s1

SMILES Code

FC1=CC=C(C=C1)S(N[C@@H](C(C)C)C(N[C@H](C=O)CC(C)C)=O)(=O)=O

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:

Calpain inhibitor VI is an inhibitor of the calcium-dependent cysteine proteases µ-calpain (calpain-1; IC50 = 7.5 nM) and m-calpain (calpain-2; IC50 = 78 nM). It also inhibits cathepsins B and L (IC50s = 15 and 1.6 nM, respectively). It is selective for these calpains and cathepsins over other cysteine and serine proteases, factor VIIa, factor Xa, trypsin, chymotrypsin, and proteasome.

In vitro activity:

SJA6017 demonstrated effective neuroprotection against MPP+-induced damage in spinal motoneurons. In VSC 4.1 cells exposed to the Parkinsonian neurotoxicant MPP+, SJA6017 mitigated the rise in intracellular free Ca2+, reduced the active form of calpain, and prevented increased levels of proteases and their activities. It also diminished elevated levels of reactive oxygen species and partially ameliorated impairment in motor proteins dynein and kinesin caused by MPP+. Reference: Neurotox Res. 2020 Oct;38(3):640-649. https://pubmed.ncbi.nlm.nih.gov/32761446/

In vivo activity:

SJA6017 may have potential in spinal cord injury treatment. In a rat spinal cord injury model, SJA6017 reduced apoptotic cell death, preserved spinal cord tissue and improved functional outcome. SJA6017 treated rats had significantly reduced tissue injury and had ameliorated recovery of limb function. Reference: J Clin Neurosci. 2008 Oct;15(10):1130-6. https://pubmed.ncbi.nlm.nih.gov/18656362/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	5.0	13.42

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 372.46 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. Samantaray S, Knaryan VH, M Del Re A, Woodward JJ, Shields DC, Azuma M, Inoue J, Ray SK, Banik NL. Cell-Permeable Calpain Inhibitor SJA6017 Provides Functional Protection to Spinal Motoneurons Exposed to MPP. Neurotox Res. 2020 Oct;38(3):640-649. doi: 10.1007/s12640-020-00264-3. Epub 2020 Aug 6. PMID: 32761446; PMCID: PMC9453439. 2. Biswas S, Harris F, Singh J, Phoenix DA. The in vitro retardation of porcine cataractogenesis by the calpain inhibitor, SJA6017. Mol Cell Biochem. 2004 Jun;261(1-2):169-73. doi: 10.1023/b:mcbi.0000028752.89886.43. PMID: 15362500. 3. Akdemir O, Uçankale M, Karaoğlan A, Barut S, Sağmanligil A, Bilguvar K, Cirakoğlu B, Sahan E, Colak A. Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. J Clin Neurosci. 2008 Oct;15(10):1130-6. doi: 10.1016/j.jocn.2007.08.011. Epub 2008 Jul 24. PMID: 18656362. 4. Tamada Y, Fukiage C, Mizutani K, Yamaguchi M, Nakamura Y, Azuma M, Shearer TR. Calpain inhibitor, SJA6017, reduces the rate of formation of selenite cataract in rats. Curr Eye Res. 2001 Apr;22(4):280-5. doi: 10.1076/ceyr.22.4.280.5505. PMID: 11462167.

In vitro protocol:

In vivo protocol:

1. Akdemir O, Uçankale M, Karaoğlan A, Barut S, Sağmanligil A, Bilguvar K, Cirakoğlu B, Sahan E, Colak A. Therapeutic efficacy of SJA6017, a calpain inhibitor, in rat spinal cord injury. J Clin Neurosci. 2008 Oct;15(10):1130-6. doi: 10.1016/j.jocn.2007.08.011. Epub 2008 Jul 24. PMID: 18656362. 2. Tamada Y, Fukiage C, Mizutani K, Yamaguchi M, Nakamura Y, Azuma M, Shearer TR. Calpain inhibitor, SJA6017, reduces the rate of formation of selenite cataract in rats. Curr Eye Res. 2001 Apr;22(4):280-5. doi: 10.1076/ceyr.22.4.280.5505. PMID: 11462167.

1: Fukiage C, Azuma M, Nakamura Y, Tamada Y, Nakamura M, Shearer TR. SJA6017, a newly synthesized peptide aldehyde inhibitor of calpain: amelioration of cataract in cultured rat lenses. Biochim Biophys Acta. 1997 Oct 24;1361(3):304-12. doi: 10.1016/s0925-4439(97)00043-4. PMID: 9375805. 2: Fukiage C, Azuma M, Nakamura Y, Tamada Y, Shearer TR. Nuclear cataract and light scattering in cultured lenses from guinea pig and rabbit. Curr Eye Res. 1998 Jun;17(6):623-35. PMID: 9663852. 3: Nakamura Y, Fukiage C, Ma H, Shih M, Azuma M, Shearer TR. Decreased sensitivity of lens-specific calpain Lp82 to calpastatin inhibitor. Exp Eye Res. 1999 Aug;69(2):155-62. doi: 10.1006/exer.1998.0686. PMID: 10433852. 4: Tamada Y, Fukiage C, Boyle DL, Azuma M, Shearer TR. Involvement of cysteine proteases in bFGF-induced angiogenesis in guinea pig and rat cornea. J Ocul Pharmacol Ther. 2000 Jun;16(3):271-83. doi: 10.1089/jop.2000.16.271. PMID: 10872924. 5: Nath R, Davis M, Probert AW, Kupina NC, Ren X, Schielke GP, Wang KK. Processing of cdk5 activator p35 to its truncated form (p25) by calpain in acutely injured neuronal cells. Biochem Biophys Res Commun. 2000 Jul 21;274(1):16-21. doi: 10.1006/bbrc.2000.3070. Erratum in: Biochem Biophys Res Commun 2000 Sep 16;276(1):390. PMID: 10903889. 6: Sakamoto YR, Nakajima TR, Fukiage CR, Sakai OR, Yoshida YR, Azuma MR, Shearer TR. Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina. Curr Eye Res. 2000 Jul;21(1):571-80. PMID: 11035539. 7: Mathur P, Gupta SK, Wegener AR, Breipohl W, Ahrend MH, Sharma YD, Gupta YK, Vajpayee RB. Comparison of various calpain inhibitors in reduction of light scattering, protein precipitation and nuclear cataract in vitro. Curr Eye Res. 2000 Dec;21(6):926-33. doi: 10.1076/ceyr.21.6.926.6990. PMID: 11262616. 8: Tamada Y, Fukiage C, Mizutani K, Yamaguchi M, Nakamura Y, Azuma M, Shearer TR. Calpain inhibitor, SJA6017, reduces the rate of formation of selenite cataract in rats. Curr Eye Res. 2001 Apr;22(4):280-5. doi: 10.1076/ceyr.22.4.280.5505. PMID: 11462167. 9: Kupina NC, Nath R, Bernath EE, Inoue J, Mitsuyoshi A, Yuen PW, Wang KK, Hall ED. The novel calpain inhibitor SJA6017 improves functional outcome after delayed administration in a mouse model of diffuse brain injury. J Neurotrauma. 2001 Nov;18(11):1229-40. doi: 10.1089/089771501317095269. PMID: 11721741. 10: Tamada Y, Fukiage C, Daibo S, Yoshida Y, Azuma M, Shearer TR. Involvement of calpain in hypoxia-induced damage in rat retina in vitro. Comp Biochem Physiol B Biochem Mol Biol. 2002 Feb;131(2):221-5. doi: 10.1016/s1096-4959(01)00489-4. PMID: 11818243. 11: Ray SK, Dixon CE, Banik NL. Molecular mechanisms in the pathogenesis of traumatic brain injury. Histol Histopathol. 2002 Oct;17(4):1137-52. doi: 10.14670/HH-17.1137. PMID: 12371142. 12: Aki T, Yoshida K, Fujimiya T. Phosphoinositide 3-kinase accelerates calpain- dependent proteolysis of fodrin during hypoxic cell death. J Biochem. 2002 Dec;132(6):921-6. doi: 10.1093/oxfordjournals.jbchem.a003305. PMID: 12473194. 13: Inoue J, Nakamura M, Cui YS, Sakai Y, Sakai O, Hill JR, Wang KK, Yuen PW. Structure-activity relationship study and drug profile of N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (SJA6017) as a potent calpain inhibitor. J Med Chem. 2003 Feb 27;46(5):868-71. doi: 10.1021/jm0201924. PMID: 12593666. 14: Nakamura M, Yamaguchi M, Sakai O, Inoue J. Exploration of cornea permeable calpain inhibitors as anticataract agents. Bioorg Med Chem. 2003 Apr 3;11(7):1371-9. doi: 10.1016/s0968-0896(02)00612-0. PMID: 12628663. 15: Sharma AK, Rohrer B. Calcium-induced calpain mediates apoptosis via caspase-3 in a mouse photoreceptor cell line. J Biol Chem. 2004 Aug 20;279(34):35564-72. doi: 10.1074/jbc.M401037200. Epub 2004 Jun 18. Retraction in: J Biol Chem. 2017 Aug 11;292(32):13186. doi: 10.1074/jbc.A117.401037. PMID: 15208318. 16: Biswas S, Harris F, Singh J, Phoenix DA. The in vitro retardation of porcine cataractogenesis by the calpain inhibitor, SJA6017. Mol Cell Biochem. 2004 Jun;261(1-2):169-73. doi: 10.1023/b:mcbi.0000028752.89886.43. PMID: 15362500. 17: Abell AD, Brown KM, Coxon JM, Jones MA, Miyamoto S, Neffe AT, Nikkel JM, Stuart BG. Synthesis and evaluation of eight-membered cyclic pseudo-dipeptides. Peptides. 2005 Feb;26(2):251-8. doi: 10.1016/j.peptides.2004.09.006. PMID: 15629536. 18: Tamada Y, Nakajima E, Nakajima T, Shearer TR, Azuma M. Proteolysis of neuronal cytoskeletal proteins by calpain contributes to rat retinal cell death induced by hypoxia. Brain Res. 2005 Jul 19;1050(1-2):148-55. doi: 10.1016/j.brainres.2005.05.048. PMID: 15979593. 19: Robertson LJ, Morton JD, Yamaguchi M, Bickerstaffe R, Shearer TR, Azuma M. Calpain may contribute to hereditary cataract formation in sheep. Invest Ophthalmol Vis Sci. 2005 Dec;46(12):4634-40. doi: 10.1167/iovs.04-1291. PMID: 16303960. 20: Shirasaki Y, Miyashita H, Yamaguchi M. Exploration of orally available calpain inhibitors. Part 3: Dipeptidyl alpha-ketoamide derivatives containing pyridine moiety. Bioorg Med Chem. 2006 Aug 15;14(16):5691-8. doi: 10.1016/j.bmc.2006.04.013. Epub 2006 May 2. PMID: 16651001.