SNJ-1945 | CAS# 854402-59-8 | Calpain Inhibitor

MedKoo Cat#: 564979 | Name: SNJ-1945

Description:

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

SNJ-1945 is a calpain inhibitor with more favorable retinal penetration, high oral bioavailability, and long half-life. SNJ1945 rescued defective function in lissencephaly. SNJ-1945 protects SH-SY5Y cells against MPP(+) and rotenone. SNJ-1945 reduces murine retinal cell death in vitro and in vivo. SNJ-1945 has good aqueous solubility, can prevents the heart from KCl arrest-reperfusion injury associated with the impairment of total Ca(2+) handling by inhibiting the proteolysis of alpha-fodrin as a cardioplegia.

Chemical Structure

SNJ-1945

CAS#854402-59-8

Theoretical Analysis

MedKoo Cat#: 564979

Name: SNJ-1945

CAS#: 854402-59-8

Chemical Formula: C25H37N3O7

Exact Mass: 491.2632

Molecular Weight: 491.59

Elemental Analysis: C, 61.08; H, 7.59; N, 8.55; O, 22.78

Price and Availability

Size	Price	Availability
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to ship
100mg	USD 750.00	Ready to ship
200mg	USD 1,250.00	Ready to ship
500mg	USD 2,650.00	Ready to ship
1g	USD 4,150.00	Ready to ship

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Synonym

SNJ1945; SNJ 1945; SNJ-1945

IUPAC/Chemical Name

((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester

InChi Key

PMEQLUMDXFJNRY-SFTDATJTSA-N

InChi Code

InChI=1S/C25H37N3O7/c1-17(2)15-21(28-25(32)35-14-13-34-12-11-33-3)23(30)27-20(16-18-7-5-4-6-8-18)22(29)24(31)26-19-9-10-19/h4-8,17,19-21H,9-16H2,1-3H3,(H,26,31)(H,27,30)(H,28,32)/t20-,21-/m0/s1

SMILES Code

O=C(OCCOCCOC)N[C@H](C(N[C@@H](CC1=CC=CC=C1)C(C(NC2CC2)=O)=O)=O)CC(C)C

Appearance

White to off-white solid powder

Purity

>97% (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

>3 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

Certificate of Analysis

View CoA: current batch, Lot#YXM91105

QC Data

View QC data: current batch, Lot#YXM91105

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

SNJ-1945 is a calpain inhibitor with retinal penetration and long half-life.

In vitro activity:

Effects of calpain inhibitor SNJ-1945 on the survival of differentiated SH-SY5Y cells following exposure to MPP+ or rotenone was tested. Cell viability assay showed that both SH-SY5Y-DA and SH-SY5Y-ChAT cells responded to both neurotoxicants in a dosedependent manner (data presented in SH-SY5Y-DA cells, Fig. 2A-B). Similar concentrations of MPP+ and rotenone in SH-SY5Y-DA and SH-SY5Y-ChAT cells were used in subsequent experiments. Three doses of the calpain inhibitor SNJ-1945 (10, 100 or 250 µM) were tested for protective capacity against MPP+ or rotenone (Fig. 2A and 2B, respectively). SNJ-1945 alone at its highest concentration (250 µM) had no overt on these cells. SNJ-1945 (100 and 250 µM) was found significantly protective against MPP+ and rotenone. Pre-treatment with SNJ-1945 (50 or 100 or 250 µM) dose-dependently attenuated the neurotoxicant-induced levels of inflammatory mediators in SH-SY5Y-ChAT cells (Fig. 6). Importantly, the novel water-soluble calpain inhibitor SNJ-1945 could significantly protect against damaging pathways including oxidative stress, inflammation, calpain-calpastatin dysregulation, and proteolysis. Reference: J Neurochem. 2014 Jul; 130(2): 280–290. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038676/

In vivo activity:

This study aimed to show the in vivo effect of oral treatment to directly asses the validity of this new calpain inhibitor SNJ-1945 as an oral therapeutic for EAE/MS. Daily oral dosing was performed on B10-PL mice with EAE starting at day 9 post induction. The disease scores of Control-vehicle (Control), EAE-vehicle (EAE), and EAE SNJ-1945 treated mice (SNJ-1945) were recorded (Figure 1). EAE vehicle-treated mice were consistent with what has been described in the literature having severe paralysis symptoms (Papenfuss et al. 2004). Overall, there was a statistically significant difference in the paralysis scores between Control-Vehicle, EAEVehicle, and EAE-SNJ-1945-treated mice. Not only did mice treated with SNJ-1945 experience significantly milder manifestations of the disease, but also the monophasic peak of paralytic signs was delayed relative to EAE-vehicle mice. Interestingly, the number of MDSCs increased upon in vivo treatment of EAE mice with SNJ-1945. This data suggests that they may have rendered an important anti-inflammatory effect in the progression of the disease (Figure 3A). Overall, it has been shown that inflammatory Th cells are reduced upon treatment with SNJ-1945 while regulatory/anti-inflammatory factors and cells are increased in mice. Taken together, these data confirm that SNJ-1945 treatment aids in suppressing the inflammatory immune arm of the disease. Both of these positive in vivo outcomes show that SNJ-1945 is a valid oral therapy for EAE mice. Reference: J Neurochem. 2014 Jul; 130(2): 268–279. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4107076/

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	0.0	0.00

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 491.59 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. Knaryan VH, Samantaray S, Park S, Azuma M, Inoue J, Banik NL. SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP(+) and rotenone. J Neurochem. 2014 Jul;130(2):280-90. doi: 10.1111/jnc.12629. Epub 2013 Dec 16. PMID: 24341912; PMCID: PMC4038676. 2. Shimazawa M, Suemori S, Inokuchi Y, Matsunaga N, Nakajima Y, Oka T, Yamamoto T, Hara H. A novel calpain inhibitor, ((1S)1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther. 2010 Feb;332(2):380-7. doi: 10.1124/jpet.109.156612. Epub 2009 Nov 12. PMID: 19910537. 3. Trager N, Smith A, Wallace Iv G, Azuma M, Inoue J, Beeson C, Haque A, Banik NL. Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. J Neurochem. 2014 Jul;130(2):268-79. doi: 10.1111/jnc.12659. Epub 2014 Feb 12. PMID: 24447070; PMCID: PMC4107076.

In vitro protocol:

In vivo protocol:

1. Shimazawa M, Suemori S, Inokuchi Y, Matsunaga N, Nakajima Y, Oka T, Yamamoto T, Hara H. A novel calpain inhibitor, ((1S)1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther. 2010 Feb;332(2):380-7. doi: 10.1124/jpet.109.156612. Epub 2009 Nov 12. PMID: 19910537. 2. Trager N, Smith A, Wallace Iv G, Azuma M, Inoue J, Beeson C, Haque A, Banik NL. Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. J Neurochem. 2014 Jul;130(2):268-79. doi: 10.1111/jnc.12659. Epub 2014 Feb 12. PMID: 24447070; PMCID: PMC4107076

1: Trager N, Smith A, Wallace Iv G, Azuma M, Inoue J, Beeson C, Haque A, Banik NL. Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. J Neurochem. 2014 Jul;130(2):268-79. doi: 10.1111/jnc.12659. Epub 2014 Feb 12. PubMed PMID: 24447070; PubMed Central PMCID: PMC4107076. 2: Knaryan VH, Samantaray S, Park S, Azuma M, Inoue J, Banik NL. SNJ-1945, a calpain inhibitor, protects SH-SY5Y cells against MPP(+) and rotenone. J Neurochem. 2014 Jul;130(2):280-90. doi: 10.1111/jnc.12629. Epub 2013 Dec 16. PubMed PMID: 24341912; PubMed Central PMCID: PMC4038676. 3: Bains M, Cebak JE, Gilmer LK, Barnes CC, Thompson SN, Geddes JW, Hall ED. Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model. J Neurochem. 2013 Apr;125(1):125-32. doi: 10.1111/jnc.12118. Epub 2013 Jan 28. PubMed PMID: 23216523. 4: Yoshikawa Y, Zhang GX, Obata K, Matsuyoshi H, Asada K, Taniguchi S, Takaki M. A cardioprotective agent of a novel calpain inhibitor, SNJ-1945, exerts beta1 actions on left ventricular mechanical work and energetics. Am J Physiol Heart Circ Physiol. 2010 Aug;299(2):H396-401. doi: 10.1152/ajpheart.00153.2010. Epub 2010 May 28. PubMed PMID: 20511411. 5: Yoshikawa Y, Zhang GX, Obata K, Ohga Y, Matsuyoshi H, Taniguchi S, Takaki M. Cardioprotective effects of a novel calpain inhibitor SNJ-1945 for reperfusion injury after cardioplegic cardiac arrest. Am J Physiol Heart Circ Physiol. 2010 Feb;298(2):H643-51. doi: 10.1152/ajpheart.00849.2009. Epub 2009 Dec 4. PubMed PMID: 19966051. 6: Shimazawa M, Suemori S, Inokuchi Y, Matsunaga N, Nakajima Y, Oka T, Yamamoto T, Hara H. A novel calpain inhibitor, ((1S)-1-((((1S)-1-Benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-me thylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945), reduces murine retinal cell death in vitro and in vivo. J Pharmacol Exp Ther. 2010 Feb;332(2):380-7. doi: 10.1124/jpet.109.156612. Epub 2009 Nov 12. PubMed PMID: 19910537. 7: Ma H, Tochigi A, Shearer TR, Azuma M. Calpain inhibitor SNJ-1945 attenuates events prior to angiogenesis in cultured human retinal endothelial cells. J Ocul Pharmacol Ther. 2009 Oct;25(5):409-14. doi: 10.1089/jop.2009.0030. PubMed PMID: 19857102; PubMed Central PMCID: PMC2958445.