IBROLIPIM

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20BrN2O4P
Molecular Weight	451.251
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCOP(=O)(CC1=CC=C(C=C1)C(=O)NC2=C(C=C(Br)C=C2)C#N)OCC

InChI

InChIKey=KPRTURMJVWXURQ-UHFFFAOYSA-N

InChI=1S/C19H20BrN2O4P/c1-3-25-27(24,26-4-2)13-14-5-7-15(8-6-14)19(23)22-18-10-9-17(20)11-16(18)12-21/h5-11H,3-4,13H2,1-2H3,(H,22,23)

HIDE SMILES / InChI

Molecular Formula	C19H20BrN2O4P
Molecular Weight	451.251
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16423620
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12847564

Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886 (ibrolipim, [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2). NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass. It was discovered, that this agent has a potentially beneficial for the treatment of hypertriglyceridemia, hypo-HDL cholesterolemia, and protection from atherosclerosis. In addition, this agent may be used in the treatment of obesity and obesity-linked health problems in postmenopausal women.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Lipoprotein lipase 1 Target ID: CHEMBL2060 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12847564	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Hypertriglyceridemia 17 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12847564	Palliative	Preclinical	Unknown Approved Use Unknown
Atherosclerosis 74 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12847564	Preventing	Preclinical	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16423620	Palliative	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effect of lipoprotein lipase activators bezafibrate and NO-1886, on B16 melanoma-induced cachexia in mice.	1999 Sep-Oct	10628360
[Lipid-lowering drugs].	2001 Dec	11778457
Effects of the lipoprotein lipase activator NO-1886 as a suppressor agent of atherosclerosis in aorta of mild diabetic rabbits.	2002	12236049
A lipoprotein lipase activator, NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats.	2002 Jul	12086697
Correlation between lipid and glycogen contents in liver and insulin resistance in high-fat-fed rats treated with the lipoprotein lipase activator NO-1886.	2002 Jun	12037738
Phosphonate O-deethylation of [4-(4-bromo-2-cyano-phenylcarbamoyl) benzyl]-phosphonic acid diethyl ester, a lipoprotein lipase-promoting agent, catalyzed by cytochrome P450 2C8 and 3A4 in human liver microsomes.	2002 Mar	11854149
Pharmacokinetics and metabolism of NO-1886, a lipoprotein lipase-promoting agent, in cynomolgus monkey.	2003 Dec	14742146
Lipoprotein lipase activator NO-1886 (ibrolipim) accelerates the mRNA expression of fatty acid oxidation-related enzymes in rat liver.	2003 Dec	14669153
Lipoprotein lipase and atherosclerosis.	2003 Mar	15320848
Lipoprotein lipase activator NO-1886.	2003 Summer	12847564
Effects of NO-1886 (Ibrolipim), a lipoprotein lipase-promoting agent, on gene induction of cytochrome P450s, carboxylesterases, and sulfotransferases in primary cultures of human hepatocytes.	2004 Dec	15681896
Lipoprotein lipase activator NO-1886 improves fatty liver caused by high-fat feeding in streptozotocin-induced diabetic rats.	2004 Feb	14767881
NO-1886 decreases ectopic lipid deposition and protects pancreatic beta cells in diet-induced diabetic swine.	2004 Mar	15012594
NO-1886 inhibits size of adipocytes, suppresses plasma levels of tumor necrosis factor-alpha and free fatty acids, improves glucose metabolism in high-fat/high-sucrose-fed miniature pigs.	2004 Mar	14726214
NO-1886 (ibrolipim), a lipoprotein lipase activator, increases the expression of uncoupling protein 3 in skeletal muscle and suppresses fat accumulation in high-fat diet-induced obesity in rats.	2005 Dec	16311090
Concomitant suppression of hyperlipidemia and intestinal polyp formation by increasing lipoprotein lipase activity in Apc-deficient mice.	2006 Apr	16606335
Assessment of induction of cytochrome P450 by NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, in primary cultures of human hepatocytes and in female rat liver.	2006 Feb	16547390
NO-1886 (ibrolipim), a lipoprotein lipase-promoting agent, accelerates the expression of UCP3 messenger RNA and ameliorates obesity in ovariectomized rats.	2006 Feb	16423620
Effects of NO-1886 on inflammation-associated cytokines in high-fat/high-sucrose/high-cholesterol diet-fed miniature pigs.	2006 Jul 1	16730700
NO-1886 upregulates ATP binding cassette transporter A1 and inhibits diet-induced atherosclerosis in Chinese Bama minipigs.	2006 Sep	16807312
Uncoupling proteins, dietary fat and the metabolic syndrome.	2006 Sep 12	16968550
Lipoprotein lipase activator ameliorates the severity of dietary steatohepatitis.	2007 Apr 27	17350593
NO-1886, a lipoprotein lipase activator, attenuates vascular smooth muscle contraction in rat aorta.	2007 Jan 12	17109854
NO-1886, a lipoprotein lipase activator, attenuates contraction of rat intestinal ring preparations.	2008 Feb	18319547
Evaluation of induction potency of new drug candidates on CYP1A2 and CYP3A4 using real-time one-step RT-PCR in primary cultures of cryopreserved human hepatocytes.	2009	19881256
Pharmacological approaches to modifying HDL: more basic science to understand HDL metabolism is necessary. Editorial to: "NO-1886 up-regulates Niemann-Pick C1 protein (NPC1) expression through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells" by Xin Ma et al.	2009 Jun	19434486
NO-1886 up-regulates Niemann-Pick C1 protein (NPC1) expression through liver X receptor alpha signaling pathway in THP-1 macrophage-derived foam cells.	2009 Jun	19229602
NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation through STAT5-dependent upregulation of IGF1 and CYP7A1.	2010 Jan	19815588
Ibrolipim increases ABCA1/G1 expression by the LXRα signaling pathway in THP-1 macrophage-derived foam cells.	2010 Oct	20871621

Patents

Sample Use Guides

In Vivo Use Guide

for rats: 100 mg/kg. The animals were fed the high-fat chow for 8 weeks

Route of Administration: Oral

In Vitro Use Guide

NO-1886 (ibrolipim) stimulated glucose consumption, glycogen synthesis and free fatty acids (FFA) absorption in insulin-resistant HepG2 cells. Maximum stimulation effects were observed with 10 µm NO-1886 for 24 h. Compared with the dimethyl sulfoxide-treated group, 2.5 µm NO-1886 or higher could induce the mRNA expression of lipoprotein lipase. Meanwhile, NO-1886 increased the protein content of P-GSK-3βser(9) and decreased the protein level of GSK-3β in insulin-resistant HepG2 cells, but NO-1886 didn't change the protein levels of PI3-Kp85 and Akt2.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:37:25 GMT 2023` Edited by `admin` on `Fri Dec 15 16:37:25 GMT 2023`
Record UNII	07H1561618
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

IBROLIPIM

Official Name

English

ibrolipim [INN]

Common Name

English

OPF009

Code

English

IBROLIPIM [USAN]

Common Name

English

OPF-009

Code

English

Diethyl [4-[(4-bromo-2-cyanophenyl)carbamoyl]benzyl]phosphonate

Systematic Name

English

PHOSPHONIC ACID, ((4-(((4-BROMO-2-CYANOPHENYL)AMINO)CARBONYL)PHENYL)METHYL)-, DIETHYL ESTER

Common Name

English

NO-1886

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C29703