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MedKoo Cat#: 530347 | Name: Sephin1
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Description:

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

Sephin1 is a selective inhibitor of a holophosphatase. Sephin1 safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis. Sephin1may have potential to safely prevent two protein misfolding diseases.

Chemical Structure

Sephin1
CAS#951441-04-6 (free base)

Theoretical Analysis

MedKoo Cat#: 530347

Name: Sephin1

CAS#: 951441-04-6 (free base)

Chemical Formula: C8H9ClN4

Exact Mass: 196.0516

Molecular Weight: 196.64

Elemental Analysis: C, 48.87; H, 4.61; Cl, 18.03; N, 28.49

Price and Availability

Size Price Availability Quantity
50mg USD 450.00 2 Weeks
100mg USD 750.00 2 Weeks
200mg USD 1,150.00 2 Weeks
500mg USD 1,950.00 2 Weeks
1g USD 2,950.00 2 Weeks
2g USD 5,250.00 2 Weeks
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Related CAS #
951441-04-6 (free base) 32597-86-7 (HCl)
Synonym
Sephin1; Sephin-1; Sephin 1; icerguastatum; icerguastat
IUPAC/Chemical Name
(E)-2-(2-Chlorobenzylidene)hydrazinecarboximidamide
InChi Key
PDWJALXSRRSUHR-LFYBBSHMSA-N
InChi Code
InChI=1S/C8H9ClN4/c9-7-4-2-1-3-6(7)5-12-13-8(10)11/h1-5H,(H4,10,11,13)/b12-5+
SMILES Code
ClC1=CC=CC=C1/C=N/NC(N)=N
Appearance
Solid powder
Purity
>95% (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:
Sephin1 safely and selectively inhibited a regulatory subunit of protein phosphatase 1 in vivo. Sephin1 selectively bound and inhibited the stress-induced PPP1R15A, but not the related and constitutive PPP1R15B, to prolong the benefit of an adaptive phospho-signaling pathway, protecting cells from otherwise lethal protein misfolding stress. In vivo, Sephin1 safely prevented the motor, morphological, and molecular defects of two otherwise unrelated protein-misfolding diseases in mice, Charcot-Marie-Tooth 1B, and amyotrophic lateral sclerosis.
In vitro activity:
Sephin1 has strong anti-excitotoxic properties with therapeutic potential unrelated to the integrated stress response. Sephin1 provides neuroprotection without adverse effects on the α2-adrenergic system. Sephin1 completely blocked NMDA-induced neuronal death and was ineffective against AMPA-induced excitotoxicity but did not protect from experimental ER stress. Sephin1 partially but significantly reduced NMDA-induced cytosolic Ca2+ increase, leading to a complete inhibition of subsequent calpain activation. Reference: Int J Mol Sci. 2020 Aug 24;21(17):6088. https://pubmed.ncbi.nlm.nih.gov/32846985/
In vivo activity:
Sephin1 has a key antitumor role. In C57BL/6 mice, Sephin1 treatment led to higher levels of integrated stress response activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. Sephin1 also inhibited the clonal expansion of tumor-specific T cells. Reference: iScience. 2023 Jan 13;26(2):105954. https://pubmed.ncbi.nlm.nih.gov/36718369/
Solvent mg/mL mM comments
Solubility
DMSO 20.0 101.71
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 196.64 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.

Recalculate based on batch purity %
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. Ruiz A, Zuazo J, Ortiz-Sanz C, Luchena C, Matute C, Alberdi E. Sephin1 Protects Neurons against Excitotoxicity Independently of the Integrated Stress Response. Int J Mol Sci. 2020 Aug 24;21(17):6088. doi: 10.3390/ijms21176088. PMID: 32846985; PMCID: PMC7504470. 2. Thapa S, Abdelaziz DH, Abdulrahman BA, Schatzl HM. Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model. Mol Neurobiol. 2020 May;57(5):2206-2219. doi: 10.1007/s12035-020-01880-y. Epub 2020 Jan 24. PMID: 31981074. 3. Chen Y, Quan S, Patil V, Kunjamma RB, Tokars HM, Leisten ED, Joy G, Wills S, Chan JR, Wong YC, Popko B. Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia. 2023 Sep;71(9):2180-2195. doi: 10.1002/glia.24386. Epub 2023 May 19. PMID: 37203250; PMCID: PMC10681276. 4. Wang R, Zhang Y, Guo S, Pei S, Guo W, Wu Z, Wang H, Wang M, Li Y, Zhu Y, Meng LH, Lang J, Jin G, Xiao Y, Hu L, Kong X. Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity. iScience. 2023 Jan 13;26(2):105954. doi: 10.1016/j.isci.2023.105954. PMID: 36718369; PMCID: PMC9883195.
In vitro protocol:
1. Ruiz A, Zuazo J, Ortiz-Sanz C, Luchena C, Matute C, Alberdi E. Sephin1 Protects Neurons against Excitotoxicity Independently of the Integrated Stress Response. Int J Mol Sci. 2020 Aug 24;21(17):6088. doi: 10.3390/ijms21176088. PMID: 32846985; PMCID: PMC7504470. 2. Thapa S, Abdelaziz DH, Abdulrahman BA, Schatzl HM. Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model. Mol Neurobiol. 2020 May;57(5):2206-2219. doi: 10.1007/s12035-020-01880-y. Epub 2020 Jan 24. PMID: 31981074.
In vivo protocol:
1. Chen Y, Quan S, Patil V, Kunjamma RB, Tokars HM, Leisten ED, Joy G, Wills S, Chan JR, Wong YC, Popko B. Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia. 2023 Sep;71(9):2180-2195. doi: 10.1002/glia.24386. Epub 2023 May 19. PMID: 37203250; PMCID: PMC10681276. 2. Wang R, Zhang Y, Guo S, Pei S, Guo W, Wu Z, Wang H, Wang M, Li Y, Zhu Y, Meng LH, Lang J, Jin G, Xiao Y, Hu L, Kong X. Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity. iScience. 2023 Jan 13;26(2):105954. doi: 10.1016/j.isci.2023.105954. PMID: 36718369; PMCID: PMC9883195.
1: Liu X, Liu M, Wu H, Tang W, Yang W, Chan TTH, Zhang L, Chen S, Xiong Z, Liang J, Wai-Yiu Si-Tou W, Shu T, Li J, Cao J, Zhong C, Sun H, Kwong TT, Leung HHW, Wong J, Bo-San Lai P, To KF, Xiang T, Jao-Yiu Sung J, Chan SL, Zhou J, Sze-Lok Cheng A. PPP1R15A-expressing monocytic MDSCs promote immunosuppressive liver microenvironment in fibrosis-associated hepatocellular carcinoma. JHEP Rep. 2024 Apr 4;6(7):101087. doi: 10.1016/j.jhepr.2024.101087. PMID: 38882672; PMCID: PMC11179254. 2: Wu Y, Zhang H, Wang Y, Zhang Y, Hong Z, Wang D. Sephin1 enhances integrated stress response and autophagy to alleviate myocardial ischemia-reperfusion injury in mice. Biomed Pharmacother. 2024 Jul;176:116869. doi: 10.1016/j.biopha.2024.116869. Epub 2024 Jun 7. PMID: 38850665. 3: Vieira FG, Tassinari VR, Kidd JD, Moreno A, Thompson K, Perrin S, Gill A, Hatzipetros T. PERK modulation, with GSK2606414, Sephin1 or salubrinal, failed to produce therapeutic benefits in the SOD1G93A mouse model of ALS. PLoS One. 2024 Feb 15;19(2):e0292190. doi: 10.1371/journal.pone.0292190. PMID: 38359044; PMCID: PMC10868768. 4: Ding ZB, Chen Y, Zheng YR, Wang YY, Deng WD, Zheng JH, Yang Q, Chen ZY, Li LH, Jiang H, Li XJ. Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis. Acta Pharmacol Sin. 2024 Apr;45(4):790-802. doi: 10.1038/s41401-023-01209-0. Epub 2024 Jan 8. PMID: 38191913; PMCID: PMC10943029. 5: Franchino CA, Brughera M, Baderna V, De Ritis D, Rocco A, Seneca S, Regal L, Podini P, D'Antonio M, Toro C, Quattrini A, Scalais E, Maltecca F. Sustained OMA1-mediated integrated stress response is beneficial for spastic ataxia type 5. Brain. 2024 Mar 1;147(3):1043-1056. doi: 10.1093/brain/awad340. PMID: 37804316; PMCID: PMC10907083. 6: Wang R, Wang M, Pei S, Zhang Y, Guo S, Guo W, Wu Z, Wang H, Li Y, Zhu Y, Meng LH, Lang J, Jin G, Xiao Y, Hu L, Kong X. Protocol for PPP1R15A-inhibited mouse model establishment with subcutaneous B16F1 tumor and single-cell analysis. STAR Protoc. 2023 Dec 15;4(4):102616. doi: 10.1016/j.xpro.2023.102616. Epub 2023 Sep 26. PMID: 37756156; PMCID: PMC10539956. 7: Chen Y, Quan S, Patil V, Kunjamma RB, Tokars HM, Leisten ED, Joy G, Wills S, Chan JR, Wong YC, Popko B. Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. Glia. 2023 Sep;71(9):2180-2195. doi: 10.1002/glia.24386. Epub 2023 May 19. PMID: 37203250; PMCID: PMC10681276. 8: Chen Y, Quan S, Patil V, Kunjamma RB, Tokars HM, Leisten ED, Chan J, Wong Y, Popko B. Insights into the mechanism of oligodendrocyte protection and remyelination enhancement by the integrated stress response. bioRxiv [Preprint]. 2023 Jan 23:2023.01.23.525156. doi: 10.1101/2023.01.23.525156. Update in: Glia. 2023 Sep;71(9):2180-2195. doi: 10.1002/glia.24386. PMID: 36747743; PMCID: PMC9900777. 9: Wang R, Zhang Y, Guo S, Pei S, Guo W, Wu Z, Wang H, Wang M, Li Y, Zhu Y, Meng LH, Lang J, Jin G, Xiao Y, Hu L, Kong X. Single-cell RNA sequencing reveals the suppressive effect of PPP1R15A inhibitor Sephin1 in antitumor immunity. iScience. 2023 Jan 13;26(2):105954. doi: 10.1016/j.isci.2023.105954. PMID: 36718369; PMCID: PMC9883195. 10: Maltsev AV, Nikiforova AB, Bal NV, Balaban PM. Amyloid Aβ25-35 Aggregates Say 'NO' to Long-Term Potentiation in the Hippocampus through Activation of Stress-Induced Phosphatase 1 and Mitochondrial Na+/Ca2+ Exchanger. Int J Mol Sci. 2022 Oct 6;23(19):11848. doi: 10.3390/ijms231911848. PMID: 36233148; PMCID: PMC9570122. 11: Witkamp D, Oudejans E, Hu-A-Ng GV, Hoogterp L, Krzywańska AM, Žnidaršič M, Marinus K, de Veij Mestdagh CF, Bartelink I, Bugiani M, van der Knaap MS, Abbink TEM. Guanabenz ameliorates disease in vanishing white matter mice in contrast to sephin1. Ann Clin Transl Neurol. 2022 Aug;9(8):1147-1162. doi: 10.1002/acn3.51611. Epub 2022 Jul 1. PMID: 35778832; PMCID: PMC9380178. 12: Bai Y, Treins C, Volpi VG, Scapin C, Ferri C, Mastrangelo R, Touvier T, Florio F, Bianchi F, Del Carro U, Baas FF, Wang D, Miniou P, Guedat P, Shy ME, D'Antonio M. Treatment with IFB-088 Improves Neuropathy in CMT1A and CMT1B Mice. Mol Neurobiol. 2022 Jul;59(7):4159-4178. doi: 10.1007/s12035-022-02838-y. Epub 2022 Apr 30. PMID: 35501630; PMCID: PMC9167212. 13: Samluk L, Ostapczuk P, Dziembowska M. Long-term mitochondrial stress induces early steps of Tau aggregation by increasing reactive oxygen species levels and affecting cellular proteostasis. Mol Biol Cell. 2022 Jul 1;33(8):ar67. doi: 10.1091/mbc.E21-11-0553. Epub 2022 Apr 21. PMID: 35446108; PMCID: PMC9635289. 14: Pernin F, Luo JXX, Cui QL, Blain M, Fernandes MGF, Yaqubi M, Srour M, Hall J, Dudley R, Jamann H, Larochelle C, Zandee SEJ, Prat A, Stratton JA, Kennedy TE, Antel JP. Diverse injury responses of human oligodendrocyte to mediators implicated in multiple sclerosis. Brain. 2022 Dec 19;145(12):4320-4333. doi: 10.1093/brain/awac075. PMID: 35202462. 15: Kitakaze K, Oyadomari M, Zhang J, Hamada Y, Takenouchi Y, Tsuboi K, Inagaki M, Tachikawa M, Fujitani Y, Okamoto Y, Oyadomari S. ATF4-mediated transcriptional regulation protects against β-cell loss during endoplasmic reticulum stress in a mouse model. Mol Metab. 2021 Dec;54:101338. doi: 10.1016/j.molmet.2021.101338. Epub 2021 Sep 20. PMID: 34547510; PMCID: PMC8487982. 16: Subréville M, Bonello-Palot N, Yahiaoui D, Beloribi-Djefaflia S, Fernandes S, Stojkovic T, Cassereau J, Péréon Y, Echaniz-Laguna A, Violleau MH, Soulages A, Louis SL, Masingue M, Magot A, Delmont E, Sacconi S, Adams D, Labeyrie C, Genestet S, Noury JB, Chanson JB, Lévy N, Juntas-Morales R, Tard C, Sole G, Attarian S. Genotype-phenotype correlation in French patients with myelin protein zero gene-related inherited neuropathy. Eur J Neurol. 2021 Sep;28(9):2913-2921. doi: 10.1111/ene.14948. Epub 2021 Jun 29. PMID: 34060176. 17: Chen Y, Kunjamma RB, Weiner M, Chan JR, Popko B. Prolonging the integrated stress response enhances CNS remyelination in an inflammatory environment. Elife. 2021 Mar 23;10:e65469. doi: 10.7554/eLife.65469. PMID: 33752802; PMCID: PMC7987340. 18: Ruiz A, Zuazo J, Ortiz-Sanz C, Luchena C, Matute C, Alberdi E. Sephin1 Protects Neurons against Excitotoxicity Independently of the Integrated Stress Response. Int J Mol Sci. 2020 Aug 24;21(17):6088. doi: 10.3390/ijms21176088. PMID: 32846985; PMCID: PMC7504470. 19: Callejo G, Pattison LA, Greenhalgh JC, Chakrabarti S, Andreopoulou E, Hockley JRF, Smith ESJ, Rahman T. In silico screening of GMQ-like compounds reveals guanabenz and sephin1 as new allosteric modulators of acid-sensing ion channel 3. Biochem Pharmacol. 2020 Apr;174:113834. doi: 10.1016/j.bcp.2020.113834. Epub 2020 Feb 3. PMID: 32027884; PMCID: PMC7068650. 20: Thapa S, Abdelaziz DH, Abdulrahman BA, Schatzl HM. Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model. Mol Neurobiol. 2020 May;57(5):2206-2219. doi: 10.1007/s12035-020-01880-y. Epub 2020 Jan 24. PMID: 31981074.