OMIGAPIL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H17NO
Molecular Weight	275.3444
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN(CC#C)CC1=CC2=C(OC3=C1C=CC=C3)C=CC=C2

InChI

InChIKey=QLMMOGWZCFQAPU-UHFFFAOYSA-N

InChI=1S/C19H17NO/c1-3-12-20(2)14-16-13-15-8-4-6-10-18(15)21-19-11-7-5-9-17(16)19/h1,4-11,13H,12,14H2,2H3

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9488718 | https://www.ncbi.nlm.nih.gov/pubmed/16505364 | https://www.ncbi.nlm.nih.gov/pubmed/17709710 | https://www.ncbi.nlm.nih.gov/pubmed/17110281 | http://www.santhera.com/health-care-professionals/our-pipeline/cmd

Omigapil (CGP 3466 or TCH346) is a structurally related analog of R-(-)-deprenyl that exhibits virtually no monoamine oxidase type B inhibiting activity but is neuroprotective in the picomolar concentration range. It binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and at subnanomolar concentrations prevent the S-nitrosylation of GAPDH, inhibit GAPDH-Siah binding and prevent the nuclear translocation of GAPDH. Omigapil demonstrated promising potential in the treatment of Parkinson's disease and motoneuron disease in animal models, however, it did not show efficacy in clinical trials. Omigapil is in development for the treatment of congenital muscular dystrophy.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glyceraldehyde-3-phosphate dehydrogenase liver 2 Target ID: CHEMBL2284 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16510976 \| https://www.ncbi.nlm.nih.gov/pubmed/16505364 \| https://www.ncbi.nlm.nih.gov/pubmed/9488718	Binding Agent 1064
apoptotic process 48 Target ID: GO:0006915 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9488718	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Congenital muscular dystrophy 2 Sources: http://www.santhera.com/health-care-professionals/our-pipeline/cmd	Primary	Phase I 428	Unknown Approved Use Unknown
Parkinson's disease 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17110281	Primary	Phase II 1132	Unknown Approved Use Unknown
Amyotrophic lateral sclerosis 41 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17709710	Primary	Phase III 656	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
15 mg 1 times / day multiple, oral Highest studied dose Dose: 15 mg, 1 times / day Route: oral Route: multiple Dose: 15 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17709710 Page: p.781	unhealthy, ADULT n = 105 Health Status: unhealthy Condition: amyotrophic lateral sclerosis Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 105 Sources: https://pubmed.ncbi.nlm.nih.gov/17709710 Page: p.781	Sources: https://pubmed.ncbi.nlm.nih.gov/17709710 Page: p.781
10 mg 1 times / day multiple, oral Studied dose Dose: 10 mg, 1 times / day Route: oral Route: multiple Dose: 10 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17110281 Page: p.1017	unhealthy, ADULT n = 73 Health Status: unhealthy Condition: Parkinson's disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 73 Sources: https://pubmed.ncbi.nlm.nih.gov/17110281 Page: p.1017	Sources: https://pubmed.ncbi.nlm.nih.gov/17110281 Page: p.1017

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00C4YO	https://www.1pchem.com/search?query=1P00C4YO
AK Scientific	X3610	https://aksci.com/item_detail.php?cat=X3610
ApexBio Technology	B5354	https://www.apexbt.com/catalogsearch/result/?q=B5354
BOC Sciences	200189-97-5	http://www.bocsci.com/description.asp?cas=200189-97-5
MolPort	MolPort-023-276-617	https://www.molport.com/shop/molecule-link/MolPort-023-276-617
MuseChem	M136998	https://www.musechem.com/product/M136998.html
MuseChem	R028763	https://www.musechem.com/product/R028763.html
ShangHai Biochempartner	BCP24057	http://www.biochempartner.com/search_BCP24057
Tocris	2966	https://www.tocris.com/search.php?Type=QuickSearch&Value=2966
Toronto Research Chemicals	C427813	https://www.trc-canada.com/product-detail/?CatNum=C427813
Toronto Research Chemicals	O640000	https://www.trc-canada.com/product-detail/?CatNum=O640000
eMolecules	28326214	https://orderbb.emolecules.com/search/#?query=28326214
eMolecules	32275638	https://orderbb.emolecules.com/search/#?query=32275638
eMolecules	45920010	https://orderbb.emolecules.com/search/#?query=45920010

PubMed

Title	Date	PubMed
CGP 3466 increases survival of cultured fetal dopaminergic neurons.	2003	12808200
Simultaneous analytical method for the determination of TCH346 and its four metabolites in human plasma by liquid chromatography/tandem mass spectrometry.	2004	14966843
CGP 3466B has no effect on disease course of (G93A) mSOD1 transgenic mice.	2004 Dec	15799550
Preclinical evidence for neuroprotection with monoamine oxidase-B inhibitors in Parkinson's disease.	2004 Oct 12	15477581
TCH346 as a neuroprotective drug in Parkinson's disease: a double-blind, randomised, controlled trial.	2006 Dec	17110281
The use of LC/MS, GC/MS, and LC/NMR hyphenated techniques to identify a drug degradation product in pharmaceutical development.	2006 Feb 24	16242883
Phase II/III randomized trial of TCH346 in patients with ALS.	2007 Aug 21	17709710
Post-translational protein modifications in type 1 diabetes: a role for the repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase?	2007 Mar	17216280
Targets for neuroprotection in Parkinson's disease.	2009 Jul	18930814

Patents

Sample Use Guides

In Vivo Use Guide

Phase II/III randomized trial of TCH346 in patients with ALS: Patients were randomly assigned in a double-blind fashion to receive either placebo or one of four doses of TCH346 (1.0, 2.5, 7.5, or 15 mg/day) administered orally once daily for at least 24 weeks.

Route of Administration: Oral

In Vitro Use Guide

1 nM omigapil (CGP 3466 protects) PAJU cells from toxicity mediated by GAPDH overexpression.

Name

Type

Language

OMIGAPIL

Official Name

English

CGP-3466

Code

English

N-(DIBENZO(B,F)OXEPIN-10-YLMETHYL)-N-METHYLPROP-2-YN-1-AMINE

Systematic Name

English

omigapil [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

260508