snj-1945 profile

((1S)-1-((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester: calpain inhibitor [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	6857712
CHEMBL ID	475920
SCHEMBL ID	356129
MeSH ID	M0509571

Synonym
((1s)-1-((((1s)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester
snj-1945
((1s)-1-((((1s)-1-benzyl-3-(cyclopropylamino)-2,3-dioxopropyl)amino)carbonyl)-3-methylbutyl)carbamic acid 5-methoxy-3-oxapentyl ester
2-(2-methoxyethoxy)ethyl (s)-1-((s)-4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-ylamino)-4-methyl-1-oxopentan-2-ylcarbamate
bdbm50263559
CHEMBL475920 ,
2-(2-methoxyethoxy)ethyl n-[(2s)-1-[[(2s)-4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate
SCHEMBL356129
snj 1945
854402-59-8
n-[(1s)-1-benzyl-3-(cyclopropylamino)-2,3-dioxopropyl]-n~2~-{[2-(2-methoxyethoxy)ethoxy]carbonyl}-l-leucinamide
snj1945
Q27459105
2-(2-methoxyethoxy)ethyl n-[(1s)-1-{[(2s)-1-(cyclopropylcarbamoyl)-1-oxo-3-phenylpropan-2-yl]carbamoyl}-3-methylbutyl]carbamate
PD193690

Excerpt	Relevance	Reference
" The effect of SNJ-1945 on α-spectrin degradation exhibited a U-shaped dose-response curve when treatment was initiated 15 min post-TBI."	( Pharmacological analysis of the cortical neuronal cytoskeletal protective efficacy of the calpain inhibitor SNJ-1945 in a mouse traumatic brain injury model. Bains, M; Barnes, CC; Cebak, JE; Geddes, JW; Gilmer, LK; Hall, ED; Thompson, SN, 2013)	0.96
" Here, we show that oral dosing with SNJ-1945, a novel water-soluble calpain inhibitor, reduces experimental autoimmune encephalomyelitis clinical scores in vivo and has a two pronged effect via anti-inflammation and protection against neurodegeneration."	( Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. Azuma, M; Banik, NL; Beeson, C; Haque, A; Inoue, J; Smith, A; Trager, N; Wallace Iv, G, 2014)	0.92
"PL mice with myelin basic protein on Days 0 and 2, and mice received twice daily oral dosing of SNJ 1945 from Day 9 until sacrificing (Day 26)."	( Calpain inhibition reduces structural and functional impairment of retinal ganglion cells in experimental optic neuritis. Azuma, M; Banik, NL; Inoue, J; Ray, SK; Rohrer, B; Samantaray, S; Smith, AW; Wheless, L, 2016)	0.43

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
Calpain-1 catalytic subunit	Homo sapiens (human)	IC50 (µMol)	0.1700	0.0002	1.0592	10.0000	AID387772
Calpain-2 catalytic subunit	Sus scrofa (pig)	IC50 (µMol)	0.0990	0.0780	0.0885	0.0990	AID387773
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
proteolysis	Calpain-1 catalytic subunit	Homo sapiens (human)
positive regulation of cell population proliferation	Calpain-1 catalytic subunit	Homo sapiens (human)
regulation of macroautophagy	Calpain-1 catalytic subunit	Homo sapiens (human)
receptor catabolic process	Calpain-1 catalytic subunit	Homo sapiens (human)
regulation of catalytic activity	Calpain-1 catalytic subunit	Homo sapiens (human)
mammary gland involution	Calpain-1 catalytic subunit	Homo sapiens (human)
self proteolysis	Calpain-1 catalytic subunit	Homo sapiens (human)
regulation of NMDA receptor activity	Calpain-1 catalytic subunit	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
calcium-dependent cysteine-type endopeptidase activity	Calpain-1 catalytic subunit	Homo sapiens (human)
calcium ion binding	Calpain-1 catalytic subunit	Homo sapiens (human)
protein binding	Calpain-1 catalytic subunit	Homo sapiens (human)
peptidase activity	Calpain-1 catalytic subunit	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
cornified envelope	Calpain-1 catalytic subunit	Homo sapiens (human)
extracellular region	Calpain-1 catalytic subunit	Homo sapiens (human)
mitochondrion	Calpain-1 catalytic subunit	Homo sapiens (human)
lysosome	Calpain-1 catalytic subunit	Homo sapiens (human)
cytosol	Calpain-1 catalytic subunit	Homo sapiens (human)
plasma membrane	Calpain-1 catalytic subunit	Homo sapiens (human)
focal adhesion	Calpain-1 catalytic subunit	Homo sapiens (human)
membrane	Calpain-1 catalytic subunit	Homo sapiens (human)
extracellular exosome	Calpain-1 catalytic subunit	Homo sapiens (human)
calpain complex	Calpain-1 catalytic subunit	Homo sapiens (human)
ficolin-1-rich granule lumen	Calpain-1 catalytic subunit	Homo sapiens (human)
cytoplasm	Calpain-1 catalytic subunit	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Assay ID	Title	Year	Journal	Article
AID387780	Drug concentration in rat retina at 10 mg/kg, po after 4 hrs	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387777	AUC (0 to 4 hrs) in Japanese white rabbit aqueous humor after ocular instillation of 1% suspension	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387774	Octanol-water partition coefficient, log P of the compound	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387781	Drug concentration in rat retina after ocular instillation	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387779	Drug concentration in rat retina at 10 mg/kg, po at Tmax time	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387775	Solubility in phosphate buffer at pH 7 and 25 degC	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387776	AUC (0 to 4 hrs) in Japanese white rabbit retina after ocular instillation of 1% suspension	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387772	Inhibition of human erythrocyte mu-calpain	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387778	Plasma AUC (0 to 4 hrs) in cynomolgus monkey at 10 mg/kg, po	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
AID387773	Inhibition of pig kidney m-calpain	2008	Bioorganic & medicinal chemistry letters, Oct-01, Volume: 18, Issue:19	Molecular design to enhance the penetration into the retina via ocular instillation.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	5 (16.13)	29.6817
2010's	23 (74.19)	24.3611
2020's	3 (9.68)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	0 (0.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	32 (100.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
carbamates [no description available]	4.86	31	amino-acid anion
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease.. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine : A tetrahydropyridine that is 1,2,3,6-tetrahydropyridine substituted by a methyl group at position 1 and a phenyl group at position 4.	2.1	1	methylpyridines; phenylpyridine; tetrahydropyridine	neurotoxin
2,2'-azobis(2-amidinopropane) 2,2'-azobis(2-amidinopropane): water-soluble free-radical initiator	2.1	1	monoazo compound
isoproterenol Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.. isoprenaline : A secondary amino compound that is noradrenaline in which one of the hydrogens attached to the nitrogen is replaced by an isopropyl group. A sympathomimetic acting almost exclusively on beta-adrenergic receptors, it is used (mainly as the hydrochloride salt) as a bronghodilator and heart stimulant for the management of a variety of cardiac disorders.	2.21	1	catechols; secondary alcohol; secondary amino compound	beta-adrenergic agonist; bronchodilator agent; cardiotonic drug; sympathomimetic agent
n,n,n',n'-tetrakis(2-pyridylmethyl)ethylenediamine N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine: a zinc ion chelating agent; structure given in first source. N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine : An N-substituted diamine that is ethylenediamine in which the four amino hydrogens are replaced by 2-pyridylmethyl groups.	2.1	1	N-substituted diamine; pyridines; tertiary amino compound	apoptosis inducer; chelator; copper chelator
rotenone Derris: A plant genus of the family FABACEAE. The root is a source of rotenoids (ROTENONE) and flavonoids. Some species of Pongamia have been reclassified to this genus and some to MILLETTIA. Some species of Deguelia have been reclassified to this genus.. rotenoid : Members of the class of tetrahydrochromenochromene that consists of a cis-fused tetrahydrochromeno[3,4-b]chromene skeleton and its substituted derivatives. The term was originally restricted to natural products, but is now also used to describe semi-synthetic and fully synthetic compounds.	7.1	1	organic heteropentacyclic compound; rotenones	antineoplastic agent; metabolite; mitochondrial NADH:ubiquinone reductase inhibitor; phytogenic insecticide; piscicide; toxin
triphenyltetrazolium triphenyltetrazolium: RN given refers to parent cpd. 2,3,5-triphenyltetrazolium : An organic cation that is tetrazole carrying three phenyl substituents at positions 2, 3 and 5.	2.04	1	organic cation
methylnitrosourea Methylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.. N-methyl-N-nitrosourea : A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by methyl and nitroso groups.	2.03	1	N-nitrosoureas	alkylating agent; carcinogenic agent; mutagen; teratogenic agent
n-methylaspartate N-Methylaspartate: An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).. N-methyl-D-aspartic acid : An aspartic acid derivative having an N-methyl substituent and D-configuration.	2.51	2	amino dicarboxylic acid; D-alpha-amino acid; D-aspartic acid derivative; secondary amino compound	neurotransmitter agent
fluorodeoxyglucose f18 Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162)	2.08	1	2-deoxy-2-((18)F)fluoro-D-glucose; 2-deoxy-2-fluoro-aldehydo-D-glucose
calpeptin [no description available]	2.13	1	amino acid amide
myelin basic protein Myelin Basic Protein: An abundant cytosolic protein that plays a critical role in the structure of multilamellar myelin. Myelin basic protein binds to the cytosolic sides of myelin cell membranes and causes a tight adhesion between opposing cell membranes.	2.13	1
11-cis-retinal Rhodopsin: A purplish-red, light-sensitive pigment found in RETINAL ROD CELLS of most vertebrates. It is a complex consisting of a molecule of ROD OPSIN and a molecule of 11-cis retinal (RETINALDEHYDE). Rhodopsin exhibits peak absorption wavelength at about 500 nm.. 11-cis-retinal : A retinal having 2E,4Z,6E,8E-double bond geometry.	2.06	1	retinal	chromophore; human metabolite; mouse metabolite
sq-23377 Ionomycin: A divalent calcium ionophore that is widely used as a tool to investigate the role of intracellular calcium in cellular processes.. ionomycin : A very long-chain fatty acid that is docosa-10,16-dienoic acid which is substituted by methyl groups at positions 4, 6, 8, 12, 14, 18 and 20, by hydroxy groups at positions 11, 19 and 21, and by a (2',5-dimethyloctahydro-2,2'-bifuran-5-yl)ethanol group at position 21. An ionophore produced by Streptomyces conglobatus, it is used in research to raise the intracellular level of Ca(2+) and as a research tool to understand Ca(2+) transport across biological membranes.	2.06	1	cyclic ether; enol; polyunsaturated fatty acid; very long-chain fatty acid	calcium ionophore; metabolite
calpain Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.	4.76	28
calpastatin calpastatin: large mol wt, heat-stable calpain inhibitor; not based on sequestering Ca++ from medium, but binding to calpain does require Ca++. calpastatin peptide Ac 184-210 : A 27-membered polypeptide comprising the sequence Ac-Asp-Pro-Met-Ser-Ser-Thr-Tyr-Ile-Glu-Glu-Leu-Gly-Lys-Arg-Glu-Val-Thr-Ile-Pro-Pro-Lys-Tyr-Arg-Glu-Leu-Leu-Ala-NH2. An acetylated synthetic peptide from human calpastatin that strongly inhibits both calpains I and II but not papain (a cysteine protease) or trypsin (a serine protease).	2.76	3	polypeptide	EC 3.4.22.52 (calpain-1) inhibitor; EC 3.4.22.53 (calpain-2) inhibitor
orabase Orabase: used in therapy of oral mucosal ulcers	2.21	1

Condition	Relationship Strength	Studies
Anoxemia [description not available]	2.8	3
Hypoxia Sub-optimal OXYGEN levels in the ambient air of living organisms.	2.8	3
Retinal Diseases Diseases involving the RETINA.	2.25	1
Branch Retinal Artery Occlusion [description not available]	2.25	1
Retinal Artery Occlusion Sudden ISCHEMIA in the RETINA due to blocked blood flow through the CENTRAL RETINAL ARTERY or its branches leading to sudden complete or partial loss of vision, respectively, in the eye.	2.25	1
Cardiovascular Stroke [description not available]	2.15	1
Injury, Myocardial Reperfusion [description not available]	2.78	3
Myocardial Infarction NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).	2.15	1
Cranial Nerve II Injuries [description not available]	2.52	2
Left Ventricular Hypertrophy [description not available]	2.21	1
Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	3.58	8
Hypertrophy, Left Ventricular Enlargement of the LEFT VENTRICLE of the heart. This increase in ventricular mass is attributed to sustained abnormal pressure or volume loads and is a contributor to cardiovascular morbidity and mortality.	2.21	1
Disease Exacerbation [description not available]	2.1	1
Allergic Encephalomyelitis [description not available]	2.8	3
MS (Multiple Sclerosis) [description not available]	2.8	3
Nerve Degeneration Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.	2.76	3
Multiple Sclerosis An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)	7.8	3
Glaucoma, Suspect [description not available]	2.46	2
Acute Disease Disease having a short and relatively severe course.	2.1	1
Ocular Hypertension A condition in which the intraocular pressure is elevated above normal and which may lead to glaucoma.	2.46	2
Retinal Degeneration A retrogressive pathological change in the retina, focal or generalized, caused by genetic defects, inflammation, trauma, vascular disease, or aging. Degeneration affecting predominantly the macula lutea of the retina is MACULAR DEGENERATION. (Newell, Ophthalmology: Principles and Concepts, 7th ed, p304)	2.97	4
Encephalopathy, Traumatic [description not available]	2.17	1
Closed Head Injuries [description not available]	2.17	1
Brain Injuries, Traumatic A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.	2.17	1
Astrocytosis [description not available]	2.13	1
Anterior Optic Neuritis [description not available]	2.13	1
Optic Neuritis Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as MULTIPLE SCLEROSIS, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis).	2.13	1
Degenerative Diseases, Central Nervous System [description not available]	2.13	1
Innate Inflammatory Response [description not available]	2.13	1
Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.	2.13	1
Neurodegenerative Diseases Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.	2.13	1
Anterior Choroidal Artery Infarction [description not available]	2.04	1
Cerebral Ischemia [description not available]	2.04	1
Cerebral Infarction The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).	2.04	1
Brain Ischemia Localized reduction of blood flow to brain tissue due to arterial obstruction or systemic hypoperfusion. This frequently occurs in conjunction with brain hypoxia (HYPOXIA, BRAIN). Prolonged ischemia is associated with BRAIN INFARCTION.	2.04	1
Left Ventricular Dysfunction [description not available]	2.47	2
Ventricular Dysfunction, Left A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.	2.47	2
Injury, Ischemia-Reperfusion [description not available]	2.06	1
Reperfusion Injury Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.	2.06	1
Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.	2.06	1
Acute Brain Injuries [description not available]	2.08	1
Brain Injuries Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.	2.08	1
Agyria [description not available]	2.08	1
Intraocular Pressure The pressure of the fluids in the eye.	2.03	1

snj-1945

Description

Cross-References

Synonyms (15)

Research Excerpts

Dosage Studied

Protein Targets (2)

Inhibition Measurements

Biological Processes (8)

Molecular Functions (4)

Ceullar Components (12)

Bioassays (10)

Research

Studies (31)

Market Indicators

Research Demand Index: 18.96

Study Types