Cutamesine HCl | CAS#165377-44-6 | sigma-1 receptor agonist

MedKoo Cat#: 319851 | Name: Cutamesine HCl

Description:

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

Cutamesine, also known as SA-4503 and AGY94806, is a sigma-1 receptor agonist under development for recovery enhancement after acute ischemic stroke. Cutamesine protects against retinal cell death in vitro and in vivo by the agonistic effect of sigma-1 receptor. Therefore, sigma-1 receptor may have a potential as a therapeutic target in retinal diseases mediated by photoreceptor degeneration. .

Chemical Structure

Cutamesine HCl

CAS#165377-44-6 (HCl)

Theoretical Analysis

MedKoo Cat#: 319851

Name: Cutamesine HCl

CAS#: 165377-44-6 (HCl)

Chemical Formula: C23H34Cl2N2O2

Exact Mass: 0.0000

Molecular Weight: 441.44

Elemental Analysis: C, 62.58; H, 7.76; Cl, 16.06; N, 6.35; O, 7.25

Price and Availability

Size	Price	Availability
10mg	USD 90.00	Ready to ship
25mg	USD 150.00	Ready to ship
50mg	USD 250.00	Ready to ship
100mg	USD 450.00	Ready to ship
200mg	USD 700.00	Ready to ship
500mg	USD 1,450.00	Ready to ship
1g	USD 2,650.00	Ready to ship

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Related CAS #

165377-44-6 (HCl) 165377-43-5 (free base)

Synonym

SA4503; SA 4503; SA-4503; AGY94806; AGY-94806; AGY 94806; Cutamesine HCl; Cutamesine hydrochloride

IUPAC/Chemical Name

1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride

InChi Key

XWOXAKBQEMQMFH-UHFFFAOYSA-N

InChi Code

InChI=1S/C23H32N2O2.2ClH/c1-26-22-11-10-21(19-23(22)27-2)12-14-25-17-15-24(16-18-25)13-6-9-20-7-4-3-5-8-20;;/h3-5,7-8,10-11,19H,6,9,12-18H2,1-2H3;2*1H

SMILES Code

COC1=CC=C(C=C1OC)CCN2CCN(CCCC3=CC=CC=C3)CC2.[H]Cl.[H]Cl

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, 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

Certificate of Analysis

View CoA: current batch, Lot#A20T09K01

QC Data

View QC data: current batch, Lot#A20T09K01

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

Cutamesine dihydrochloride (SA4503 dihydrochloride; AGY94806 dihydrochloride) is a potent Sigma 1 receptor agonist with an IC50 of 17.4 nM in guinea pig brain membranes.

In vitro activity:

Cutamesine was examined to see whether it protected the 661W cells against light-induced cell death. Representative photographs of the Hoechst 33342 and PI staining of the 661W cells pretreated with cutamesine and/or BD-1047 are shown in Fig. 1A. Hoechst 33342 stains all cells (both live and dead), whereas PI stains only dead cells. Pretreatment with 10 μM cutamesine protected against light-induced cell death (Fig. 1B), and the protective effect significantly disappeared after treatment with BD-1047, a sigma-1 receptor antagonist, at 1 μM (Fig. 1C). To investigate the expression of sigma-1 receptor in 661W cells and the effect of cutamesine, western blot analysis was used. Sigma-1 receptor protein expressed in 661W cells, and the expression was significantly decreased by light exposure. Cutamesine at 10 μM significantly prevented the decreased expression of sigma-1 receptor protein (Fig. 2). Reference: Exp Eye Res. 2015 Mar;132:64-72. https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(15)00024-X

In vivo activity:

The effects of cutamesine on light-induced retinal dysfunction were examined by electrophysiological analysis. The a-wave shows the function of the photoreceptors and the b-wave reflects the function of bipolar cells and Müller cells (Fig. 5A). Amplitudes of the a- and b-waves were significantly reduced five days after 8000 lux light exposure for 3 h. The decreases in the a- and b-wave amplitudes were significantly recovered by intravitreal injection of cutamesine (50 or 500 μM, 2 μL) compared with the vehicle-treated group (Fig. 5B). Representative entire retinal images were obtained five days after light exposure for histological evaluation (Fig. 6A). The ONL was remarkably thinner in the light-irradiated retina than in the normal retina (Fig. 6A). Cutamesine prevented the damage induced by light exposure (Fig. 6B). The thickness of the ONL was measured in 240-μm steps; the data were averaged and are shown in Fig. 6C. Cutamesine significantly protected the retinal damage in a dose-dependent manner. Furthermore, the protective effect of cutamesine (500 μM, 2 μL) on light-induced ONL thinning was significantly eliminated by co-administration with BD-1047 (500 μM), a sima-1 receptor antagonist (Fig. 7). On the other hand, BD-1047 alone did not show any effects on the light damages. Reference: Exp Eye Res. 2015 Mar;132:64-72. https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(15)00024-X

	Solvent	mg/mL	mM	comments
Solubility
	DMSO	30.0	67.96

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 441.44 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:

In vivo protocol:

1. Shimazawa M, Sugitani S, Inoue Y, Tsuruma K, Hara H. Effect of a sigma-1 receptor agonist, cutamesine dihydrochloride (SA4503), on photoreceptor cell death against light-induced damage. Exp Eye Res. 2015 Mar;132:64-72. doi: 10.1016/j.exer.2015.01.017. Epub 2015 Jan 20. PMID: 25616094. 2. Qin J, Wang P, Li Y, Yao L, Liu Y, Yu T, Lin J, Fang X, Huang Z. Activation of Sigma-1 Receptor by Cutamesine Attenuates Neuronal Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in a Rat Model of Asphyxia Cardiac Arrest. Shock. 2019 Jan;51(1):105-113. doi: 10.1097/SHK.0000000000001119. PMID: 29424796.

1: Ramakrishnan NK, Schepers M, Luurtsema G, Nyakas CJ, Elsinga PH, Ishiwata K, Dierckx RA, van Waarde A. Cutamesine Overcomes REM Sleep Deprivation-Induced Memory Loss: Relationship to Sigma-1 Receptor Occupancy. Mol Imaging Biol. 2015 Jun;17(3):364-72. doi: 10.1007/s11307-014-0808-2. PMID: 25449772. 2: Tanji C, Hashimoto M, Furuya T, Saito J, Miyamoto T, Koda M. Sigma 1 receptor agonist cutamesine promotes plasticity of serotonergic boutons in lumbar enlargement in spinal cord injured rats. Neurosci Lett. 2021 Aug 10;759:135971. doi: 10.1016/j.neulet.2021.135971. Epub 2021 May 21. PMID: 34023415. 3: Yamashita D, Sun GW, Cui Y, Mita S, Otsuki N, Kanzaki S, Nibu K, Ogawa K, Matsunaga T. Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss. J Neurosci Res. 2015 May;93(5):788-95. doi: 10.1002/jnr.23543. Epub 2015 Jan 22. PMID: 25612541. 4: Shimazawa M, Sugitani S, Inoue Y, Tsuruma K, Hara H. Effect of a sigma-1 receptor agonist, cutamesine dihydrochloride (SA4503), on photoreceptor cell death against light-induced damage. Exp Eye Res. 2015 Mar;132:64-72. doi: 10.1016/j.exer.2015.01.017. Epub 2015 Jan 20. PMID: 25616094. 5: Urfer R, Moebius HJ, Skoloudik D, Santamarina E, Sato W, Mita S, Muir KW; Cutamesine Stroke Recovery Study Group. Phase II trial of the Sigma-1 receptor agonist cutamesine (SA4503) for recovery enhancement after acute ischemic stroke. Stroke. 2014 Nov;45(11):3304-10. doi: 10.1161/STROKEAHA.114.005835. Epub 2014 Sep 30. PMID: 25270629. 6: Qin J, Wang P, Li Y, Yao L, Liu Y, Yu T, Lin J, Fang X, Huang Z. Activation of Sigma-1 Receptor by Cutamesine Attenuates Neuronal Apoptosis by Inhibiting Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in a Rat Model of Asphyxia Cardiac Arrest. Shock. 2019 Jan;51(1):105-113. doi: 10.1097/SHK.0000000000001119. PMID: 29424796. 7: Niitsu T, Iyo M, Hashimoto K. Sigma-1 receptor agonists as therapeutic drugs for cognitive impairment in neuropsychiatric diseases. Curr Pharm Des. 2012;18(7):875-83. doi: 10.2174/138161212799436476. PMID: 22288409. 8: Fujimoto M, Hayashi T, Urfer R, Mita S, Su TP. Sigma-1 receptor chaperones regulate the secretion of brain-derived neurotrophic factor. Synapse. 2012 Jul;66(7):630-9. doi: 10.1002/syn.21549. Epub 2012 Mar 16. PMID: 22337473; PMCID: PMC3824965. 9: Hashimoto K. Repurposing of CNS drugs to treat COVID-19 infection: targeting the sigma-1 receptor. Eur Arch Psychiatry Clin Neurosci. 2021 Mar;271(2):249-258. doi: 10.1007/s00406-020-01231-x. Epub 2021 Jan 5. PMID: 33403480; PMCID: PMC7785036. 10: Skuza G, Wedzony K. Behavioral pharmacology of sigma-ligands. Pharmacopsychiatry. 2004 Nov;37 Suppl 3:S183-8. doi: 10.1055/s-2004-832676. PMID: 15547784. 11: Skuza G. Potential antidepressant activity of sigma ligands. Pol J Pharmacol. 2003 Nov-Dec;55(6):923-34. PMID: 14730086. 12: Toyohara J, Sakata M, Ishiwata K. Imaging of sigma1 receptors in the human brain using PET and [11C]SA4503. Cent Nerv Syst Agents Med Chem. 2009 Sep;9(3):190-6. doi: 10.2174/1871524910909030190. PMID: 20021353. 13: Hirano K, Tagashira H, Fukunaga K. [Cardioprotective effect of the selective sigma-1 receptor agonist, SA4503]. Yakugaku Zasshi. 2014;134(6):707-13. Japanese. doi: 10.1248/yakushi.13-00255-3. PMID: 24882645. 14: Maher CM, Thomas JD, Haas DA, Longen CG, Oyer HM, Tong JY, Kim FJ. Small- Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1. Mol Cancer Res. 2018 Feb;16(2):243-255. doi: 10.1158/1541-7786.MCR-17-0166. Epub 2017 Nov 8. PMID: 29117944. 15: Ahmed H, Gisler L, Elghazawy NH, Keller C, Sippl W, Liang SH, Haider A, Ametamey SM. Development and Validation of [3H]OF-NB1 for Preclinical Assessment of GluN1/2B Candidate Drugs. Pharmaceuticals (Basel). 2022 Aug 2;15(8):960. doi: 10.3390/ph15080960. PMID: 36015108; PMCID: PMC9416150. 16: Hirata Y, Yamamoto H, Atta MS, Mahmoud S, Oh-hashi K, Kiuchi K. Chloroquine inhibits glutamate-induced death of a neuronal cell line by reducing reactive oxygen species through sigma-1 receptor. J Neurochem. 2011 Nov;119(4):839-47. doi: 10.1111/j.1471-4159.2011.07464.x. Epub 2011 Oct 3. PMID: 21883227. 17: Shinoda Y, Tagashira H, Bhuiyan MS, Hasegawa H, Kanai H, Zhang C, Han F, Fukunaga K. Corticosteroids Mediate Heart Failure-Induced Depression through Reduced σ1-Receptor Expression. PLoS One. 2016 Oct 14;11(10):e0163992. doi: 10.1371/journal.pone.0163992. PMID: 27741227; PMCID: PMC5065174. 18: Shigeno T, Kozaka T, Kitamura Y, Ogawa K, Taki J, Kinuya S, Shiba K. In vitro and in vivo evaluation of [125/123I]-2-[4-(2-iodophenyl)piperid ino]cyclopentanol([125/123I]-OI5V) as a potential sigma-1 receptor ligand for SPECT. Ann Nucl Med. 2021 Feb;35(2):167-175. doi: 10.1007/s12149-020-01552-w. Epub 2021 Jan 8. PMID: 33417152. 19: Ramakrishnan NK, Visser AK, Rybczynska AA, Nyakas CJ, Luiten PG, Kwizera C, Sijbesma JW, Elsinga PH, Ishiwata K, Dierckx RA, van Waarde A. Sigma-1 Agonist Binding in the Aging Rat Brain: a MicroPET Study with [(11)C]SA4503. Mol Imaging Biol. 2016 Aug;18(4):588-97. doi: 10.1007/s11307-015-0917-6. PMID: 26637208; PMCID: PMC4927617. 20: Tomohisa M, Junpei O, Aki M, Masato H, Mika F, Kazumi Y, Teruo H, Tsutomu S. Possible involvement of the Sigma-1 receptor chaperone in chemotherapeutic- induced neuropathic pain. Synapse. 2015 Nov;69(11):526-32. doi: 10.1002/syn.21844. Epub 2015 Sep 8. PMID: 26234785.