OXFENICINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C8H9NO3
Molecular Weight	167.162
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

N[C@H](C(O)=O)C1=CC=C(O)C=C1

InChI

InChIKey=LJCWONGJFPCTTL-ZETCQYMHSA-N

InChI=1S/C8H9NO3/c9-7(8(11)12)5-1-3-6(10)4-2-5/h1-4,7,10H,9H2,(H,11,12)/t7-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/4004784 | https://www.ncbi.nlm.nih.gov/pubmed/27558315

Oxfenicine is a CPT-1b-specific inhibitor. It must be transaminated to its active form, 4-hydroxyphenyl-glyoxylate, which is competitive with carnitine, preventing the formation of acylcarnitine. Because CPT-1b shows the highest sensitivity to 4-hydroxyphenyl-glyoxylate, inhibition of fatty acid oxidation by oxfenicine takes place selectively in those tissues that express this CPT isoform. It may be effective for treating noninsulin-dependent diabetes mellitus which is characterized by elevated fatty acid levels and obesity. In 1980 it was also tested in preclinical models of angina pectoris and ischemia.

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Carnitine O-palmitoyltransferase 1, muscle isoform 15 Target ID: Q92523 Gene ID: 1375.0 Gene Symbol: CPT1B Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/27558315	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27558315	Preventing	Preclinical	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/27558315	Primary	Preclinical	Unknown Approved Use Unknown
Angina pectoris 106 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7274235	Primary	Preclinical	Unknown Approved Use Unknown
Ischemia 16 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7432098	Primary	Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Incorporation of glucose analogs by GtfE and GtfD from the vancomycin biosynthetic pathway to generate variant glycopeptides.	2002 Dec	12498883
Palmitate-induced cardiac apoptosis is mediated through CPT-1 but not influenced by glucose and insulin.	2002 Feb	11788422
The activation of metabotropic glutamate receptors differentially affects GABA and alpha-melanocyte stimulating hormone release from the hypothalamus and the posterior pituitary of male rats.	2002 Jul 19	12098644
Modeling and kinetic analysis of the reaction system using whole cells with separately and co-expressed D-hydantoinase and N-carbamoylase.	2002 Jun 30	12001170
Equilibrium modeling of extractive enzymatic hydrolysis of penicillin G with concomitant 6-aminopenicillanic acid crystallization.	2002 May 20	11948446
Fatty acids are important for the Frank-Starling mechanism and Gregg effect but not for catecholamine response in isolated rat hearts.	2002 Nov	12392496
Inhibitory effects in the side reactions occurring during the enzymic synthesis of amoxicillin: p-hydroxyphenylglycine methyl ester and amoxicillin hydrolysis.	2003 Aug	12689339
Role of the fuel utilized by tissues on coronary vessel response to physical stimuli in isolated rat hearts.	2004	14984311
Engineering p-hydroxyphenylpyruvate dioxygenase to a p-hydroxymandelate synthase and evidence for the proposed benzene oxide intermediate in homogentisate formation.	2004 Jan 27	14730970
Dissociation between metabolic and efficiency effects of perhexiline in normoxic rat myocardium.	2005 Dec	16306812
Regulation of pyruvate dehydrogenase activity and citric acid cycle intermediates during high cardiac power generation.	2005 Jan 15	15550462
Inhibition of carnitine-acyl transferase I by oxfenicine studied in vivo with [11C]-labeled fatty acids.	2005 Jul	15982580
Carnitine palmitoyl transferase-I inhibition prevents ventricular remodeling and delays decompensation in pacing-induced heart failure.	2005 Jun 1	15914110
Fatty acid oxidation inhibition with PPARalpha activation (FOXIB/PPARalpha) for normalizing gene expression in heart failure?	2005 Jun 1	15914105
Sequential activation of caspases and synergistic beta-cell cytotoxicity by palmitate and anti-Fas antibodies.	2006 Aug 22	16707142
The enduracidin biosynthetic gene cluster from Streptomyces fungicidicus.	2006 Oct	17005978
Modification of myocardial substrate use as a therapy for heart failure.	2006 Sep	16932766
Racemization in suzuki couplings: a quantitative study using 4-hydroxyphenylglycine and tyrosine derivatives as probe molecules.	2007 Feb 2	17253834
Oxidative phenol coupling reactions catalyzed by OxyB: a cytochrome P450 from the vancomycin producing organism. implications for vancomycin biosynthesis.	2007 May 30	17477533
Facile immobilization of evolved agrobacterium radiobacter carbamoylase with high thermal and oxidative stability.	2008 Aug 13	18636689
Exploring the substrate specificity of OxyB, a phenol coupling P450 enzyme involved in vancomycin biosynthesis.	2008 Aug 21	18688478
Metabolic response to an acute jump in cardiac workload: effects on malonyl-CoA, mechanical efficiency, and fatty acid oxidation.	2008 Feb	18083904
Role of glucose metabolism in the recovery of postischemic LV mechanical function: effects of insulin and other metabolic modulators.	2008 Jun	18408129
Use of the SPhos ligand to suppress racemization in arylpinacolboronate ester Suzuki couplings involving alpha-amino acids. Synthesis of biaryl derivatives of 4-hydroxyphenylglycine, tyrosine, and tryptophan.	2009 Dec 4	19863122
Efficient biocatalytic production of D-4-hydroxyphenylglycine by whole cells of recombinant Ralstonia pickettii.	2009 Nov	20140718
Differential proteomic analysis highlights metabolic strategies associated with balhimycin production in Amycolatopsis balhimycina chemostat cultivations.	2010 Nov 26	21110849

Patents

Sample Use Guides

In Vivo Use Guide

In a preclinical study, rats were given a daily intraperitoneal injection of oxfenicine (150 mg/kg body wt) for 3 weeks.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Rat adipocytes were treated with various concentrations of oxfenicine (100 uM or 1 mM) for 2 h at 37 Degrees Celsius with gentle agitation. In cells treated with 1 mM oxfenicine, palmitate oxidation was significantly reduced by 50% compared with control cells. Isoproterenol-stimulated lipolysis was significantly decreased by 20% and 12% in epididymal adipocytes following treatment with 100 uM and 1 mM oxfenicine, respectively. Similarly, in subcutaneous inguinal adipocytes treatment with 100 uM and 1 mM of oxfenicine decreased stimulated lipolysis by 8% and 18%, respectively. Basal and insulin-stimulated glucose incorporation into lipids, the measure for lipogenesis, was reduced by 39% and 31%, respectively, in epididymal adipocytes following treatment with 1 mM oxfenicine. In adipocytes from the subcutaneous inguinal fat depot, the incorporation of glucose into lipids was also reduced by 41% under insulin-stimulated conditions, following 1 mM oxfenicine treatment

Name

Type

Language

OXFENICINE

Official Name

English

(S)-(4-HYDROXYPHENYL)GLYCINE

Common Name

English

UK-25,842

Code

English

OXFENICINE [USAN]

Common Name

English

(2R)-2-AMINO-2-(4-HYDROXYPHENYL)ACETIC ACID

Systematic Name

English

BENZENEACETIC ACID, .ALPHA.-AMINO-4-HYDROXY-, (S)-

Common Name

English

AMOXICILLIN SODIUM IMPURITY I [EP IMPURITY]

Common Name

English

UK-25842

Code

English

oxfenicine [INN]

Common Name

English

L-2-(P-HYDROXYPHENYL)GLYCINE

Common Name

English

4-HYDROXYPHENYLGLYCINE, (S)-

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2079