ICERGUASTAT ACETATE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C8H9ClN4.C2H4O2
Molecular Weight	256.689
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(O)=O.NC(=N)N\N=C\C1=CC=CC=C1Cl

InChI

InChIKey=WEXITTWZMLUGNU-NKPNRJPBSA-N

InChI=1S/C8H9ClN4.C2H4O2/c9-7-4-2-1-3-6(7)5-12-13-8(10)11;1-2(3)4/h1-5H,(H4,10,11,13);1H3,(H,3,4)/b12-5+;

HIDE SMILES / InChI

Molecular Formula	C2H4O2
Molecular Weight	60.052
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Molecular Formula	C8H9ClN4
Molecular Weight	196.637
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	1
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25859045
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/27353344 | https://www.google.com/patents/WO2014108520A1

Sephin1 is a guanabenz derivative that binds to and inhibits a regulatory subunit of the stress-induced protein phosphatase 1 (PPP1R15A), but not the constitutive PPP1R15B, and lacks beta2-adrenergic activity. Phosphorylation of eIF2α, α subunit of eukaryotic translation initiation factor 2, reduces protein synthesis and prevents the accumulation of misfolded protein in the endoplasmic reticulum (ER). PPP1R15A recruits the serine/threonine-protein phosphatase PP1 to dephosphorylate eIF2α, so inhibiting PPP1R15A activity prolongs the phosphorylation of eIF2α and aids in its prevention of the accumulation of misfolded protein. In vitro, Sephin1 protected cells from lethal protein misfolding and cytotoxic ER stress. In vivo Sephin1 prevented Charcot-Marie-Tooth 1B and ALS diseases in mice.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein phosphatase 1 regulatory subunit 15A 2 Target ID: O75807 Gene ID: 23645.0 Gene Symbol: PPP1R15A Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/25859045	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Dejerine-sottas syndrome 2 Sources: https://www.google.com/patents/WO2014108520A1	Primary	Basic research	Unknown Approved Use Unknown
Retinitis pigmentosa 10 Sources: https://www.google.com/patents/WO2014108520A1	Primary	Basic research	Unknown Approved Use Unknown
Diabetic retinopathy 17 Sources: https://www.google.com/patents/WO2014108520A1	Primary	Basic research	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Iminoguanidines as Allosteric Inhibitors of the Iron-Regulated Heme Oxygenase (HemO) of Pseudomonas aeruginosa.	2016 Jul 28	27353344

Patents

Sample Use Guides

In Vivo Use Guide

Mice were treated orally with Sephin1 (1 mg/kg) or vehicle twice a day, from postnatal days 28 to 61.

Route of Administration: Oral

In Vitro Use Guide

Cells were plated in 24-well plates at a density of 15,000 (HeLa) or 12,000 cells/ml (MEFs) 24 hours prior to treatment. ER stress was elicited by addition of fresh media containing 2.5 µg/ml tunicamycin (Sigma-Aldrich). Sephin1 were dissolved in DMSO and added at 50mkM. Cell viability was assessed by measuring the reduction of WST-8 [2-(2-methoxy-4-nitrophenyl)-3-(4- nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium] into formazan using Cell viability Counting Kit-8 (Dojindo) according to the supplier’s recommendation, 48 hours after tunicamycin treatment.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 12:44:43 GMT 2023` Edited by `admin` on `Sat Dec 16 12:44:43 GMT 2023`
Record UNII	JDD15DX7JF
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

ICERGUASTAT ACETATE

Common Name

English

HYDRAZINECARBOXIMIDAMIDE, 2-((2-CHLOROPHENYL)METHYLENE)-, ACETATE (1:1)

Systematic Name

English

IFB-088 ACETATE

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/15/1598