PONALRESTAT

Details

Stereochemistry	ACHIRAL
Molecular Formula	C17H12BrFN2O3
Molecular Weight	391.191
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC(=O)CC1=NN(CC2=C(F)C=C(Br)C=C2)C(=O)C3=CC=CC=C13

InChI

InChIKey=LKBFFDOJUKLQNY-UHFFFAOYSA-N

InChI=1S/C17H12BrFN2O3/c18-11-6-5-10(14(19)7-11)9-21-17(24)13-4-2-1-3-12(13)15(20-21)8-16(22)23/h1-7H,8-9H2,(H,22,23)

HIDE SMILES / InChI

Description
Sources: https://adisinsight.springer.com/drugs/800000017 | https://www.ncbi.nlm.nih.gov/pubmed/24663124 | https://www.ncbi.nlm.nih.gov/pubmed/10628361 | https://www.ncbi.nlm.nih.gov/pubmed/2105733 | Jucker, E. (2013) Progress in Drug Research, page 137, retrieved from: https://books.google.ru/books?id=wZz5BwAAQBAJ

Ponalrestat is the inhibitor of aldehyde reductase 2 from a number of sources. Ponalrestat blunted Prostaglandin F2 alpha synthesis by preadipocytes in basal and stimulated conditions. Ponalrestat suppresses IL-1 production both in vitro and in vivo, and inhibits the cachectic symptoms induced by colon26 adenocarcinoma in mice, suggesting that ponalrestat has a therapeutic potential for the treatment of cancer cachexia. In a 4-week study of 29 neuropathic diabetics treated with ponalrestat peripheral neuropathy did not improve during treatment. In a 6-week study of 21 diabetics without neuropathy, although vagal function improved in patients with autonomic neuropathy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Aldose reductase 44 Target ID: CHEMBL1900 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17870536	Inhibitor 8297		56.5 nM [IC50]

PubMed

Title	Date	PubMed
Effect of lipoprotein lipase activators bezafibrate and NO-1886, on B16 melanoma-induced cachexia in mice.	1999 Sep-Oct	10628360
Nitric oxide up-regulates aldose reductase expression in rat vascular smooth muscle cells: a potential role for aldose reductase in vascular remodeling.	2000 Apr	10727516
EGF receptor-ERK pathway is the major signaling pathway that mediates upregulation of aldose reductase expression under oxidative stress.	2001 Jul 15	11440832
Substrate-induced up-regulation of aldose reductase by methylglyoxal, a reactive oxoaldehyde elevated in diabetes.	2002 May	11961137
Synthesis and antimycobacterial evaluation of novel Phthalazin-4-ylacetamides against log- and starved phase cultures.	2010 Apr	20148903
The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium.	2011 Jan	20943776
The Prostaglandin F Synthase Activity of the Human Aldose Reductase AKR1B1 Brings New Lenses to Look at Pathologic Conditions.	2012	22654757
Aldo-keto reductases protect lung adenocarcinoma cells from the acute toxicity of B[a]P-7,8-trans-dihydrodiol.	2012 Jan 13	22053912
Prostaglandin (PG) F2 alpha synthesis in human subcutaneous and omental adipose tissue: modulation by inflammatory cytokines and role of the human aldose reductase AKR1B1.	2014	24663124

Sample Use Guides

In Vivo Use Guide

600 mg once daily for 2 weeks

Route of Administration: Oral

Name

Type

Language

PONALRESTAT

Official Name

English

PONALRESTAT [MART.]

Common Name

English

PONALRESTAT [USAN]

Common Name

English

3-(4-Bromo-2-fluorobenzyl)-3,4-dihydro-4-oxo-1-phthalazineacetic acid

Systematic Name

English

ICI-128436

Code

English

1-PHTHALAZINEACETIC ACID, 3-((4-BROMO-2-FLUOROPHENYL)METHYL)-3,4-DIHYDRO-4-OXO-

Common Name

English

ponalrestat [INN]

Common Name

English

ICI 128,436

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C72880