ACIFRAN

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H10O4
Molecular Weight	218.2054
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1(OC(=CC1=O)C(O)=O)C2=CC=CC=C2

InChI

InChIKey=DFDGRKNOFOJBAJ-UHFFFAOYSA-N

InChI=1S/C12H10O4/c1-12(8-5-3-2-4-6-8)10(13)7-9(16-12)11(14)15/h2-7H,1H3,(H,14,15)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389067 | https://www.ncbi.nlm.nih.gov/pubmed/21454438 | https://www.ncbi.nlm.nih.gov/pubmed/17358052 | http://adis.springer.com/drugs/800000311https://www.ncbi.nlm.nih.gov/pubmed/12522134
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/16389067 | http://adisinsight.springer.com/drugs/800000311 | https://www.ncbi.nlm.nih.gov/pubmed/6818976 | https://www.ncbi.nlm.nih.gov/pubmed/3314798

Acifran (AY-25,712), an uncommercialized Ayerst compound exerting lipid-lowering activity in vivo, has been shown to also elicit similar effects as niacin in preliminary clinical testing and has been shown to bind to both high affinity (HM74A; GPR109A) and low affinity (HM74; GPR109B) niacin receptors. The EC50 values of the separated acifran enantiomers for the GPR109a and 109b receptors showed that, as with acifran itself, the (+)-enantiomers were essentially twice as active as the racemic mixtures, whereas the activity of the (-)-enantiomers was more variable and highly dependent on purity. S-enantiomer of acifran is the active principle. All of the activity of racemic acifran could be attributed to the (S)-enantiomer, and hence, from this precedent, (+)-enantiomers would be assigned to the S-configuration. However, the absolute configuration was not confirmed experimentally.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Hydroxycarboxylic acid receptor 2 32 Target ID: CHEMBL3785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12522134 \| https://www.ncbi.nlm.nih.gov/pubmed/16389067	Agonist 2678	2.1 µM [EC50]
HM74 nicotinic acid GPCR 17 Target ID: CHEMBL4421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12522134 \| https://www.ncbi.nlm.nih.gov/pubmed/16389067	Agonist 2678	20.0 µM [EC50]
Hydroxycarboxylic acid receptor 2 32 Target ID: CHEMBL3785 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17358052	Agonist 2678	0.52 µM [EC50]
HM74 nicotinic acid GPCR 17 Target ID: CHEMBL4421 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17358052	Agonist 2678	3.0 µM [EC50]

Conditions

Condition	Modality	Highest Phase	Product
Hyperlipidemia 80 Sources: https://www.ncbi.nlm.nih.gov/pubmed/4028627 https://www.ncbi.nlm.nih.gov/pubmed/3314798	Primary	Phase III 656	Unknown Approved Use Unknown
Unknown 2578
Hyperlipidemia 80 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16389067	Primary	Preclinical	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
5.22 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
4.26 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

AUC

Value	Dose	Co-administered	Analyte	Population
16.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
15.6 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
12.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2295219	200 mg 2 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered:		ACIFRAN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

Doses

Dose	Population	Adverse events
300 mg 3 times / day multiple, oral Highest studied dose Dose: 300 mg, 3 times / day Route: oral Route: multiple Dose: 300 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/4028627 Page: p.315	unhealthy, ADULT n = 13 Health Status: unhealthy Condition: hyperlipoproteinemia Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 13 Sources: https://pubmed.ncbi.nlm.nih.gov/4028627 Page: p.315	Sources: https://pubmed.ncbi.nlm.nih.gov/4028627 Page: p.315

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY569006	https://www.001chemical.com/chem/72420-38-3
3A SpeedChemical Inc	SP-13721	http://www.speedchemical.com/products2_id_4743.html
3B Scientific (Wuhan) Corp	3B3-019691	http://www.3bsc.com/index/pro_info.php?id=42366
AHH Chemical co.,ltd	MT-46595	http://www.ahhchemical.com/product/MT-46595.html
Alfa Chemistry	72420-38-3	https://www.alfa-chemistry.com/cas_72420-38-3.htm
Ambinter	Amb18132707	http://www.ambinter.com/reference/18132707
Aurora Fine Chemicals LLC	A07.187.013	http://online.aurorafinechemicals.com/info?ID=A07.187.013
Aurora Fine Chemicals LLC	K16.774.694	http://online.aurorafinechemicals.com/info?ID=K16.774.694
BOC Sciences	72420-38-3	https://www.bocsci.com/acifran-cas-72420-38-3-item-42334.html
BioCrick	BCC7170	http://www.biocrick.com/Acifran-BCC7170.html
ChemMol	49403132	http://www.chemmol.com/chemmol/49403132.html
ChemMol	97900674	http://www.chemmol.com/chemmol/97900674.html
DC Chemicals	DC34706	http://www.dcchemicals.com//product_show-Acifran.html
Finetech	FT-0641407	http://www.finetechnology-ind.com/prod/detail/pub/72420-38-3.html
Lab Network	LN00334025	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334025
MolPort	MolPort-003-666-847	https://www.molport.com/shop/molecule-link/MolPort-003-666-847
Molcore	MC569006	https://www.molcore.com/product/72420-38-3
MuseChem	I010456	https://www.musechem.com/product/I010456.html
Sigma-Aldrich	PH003214_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/ph003214
Smolecule	S517072	http://www.smolecule.com/products/s517072
THE BioTek	bt-257395	https://www.thebiotek.com/product/inhibitors/bt-257395
Tocris	1762	https://www.tocris.com/products/acifran_1762
eNovation Chemicals	D672139	https://www.enovationchem.com/ProductDetails.asp?ProductID=D672139

PubMed

Title	Date	PubMed
Identification of a nicotinic acid receptor: is this the molecular target for the oldest lipid-lowering drug?	2004 Mar	15083592
(D)-beta-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G.	2005 Jul 22	15929991
Triglyceride modulation by acifran analogs: activity towards the niacin high and low affinity G protein-coupled receptors HM74A and HM74.	2006 Feb 10	16389067
Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways.	2006 Feb 28	16386710
Analogues of acifran: agonists of the high and low affinity niacin receptors, GPR109a and GPR109b.	2007 Apr 5	17358052
International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B).	2011 Jun	21454438

Patents

Sample Use Guides

In Vivo Use Guide

neither 1 nor 10 mg/kg (R)-acifran ((-)-enantiomers would be assigned to the R-configuration) decrease serum triglycerides in fructose-fed rats

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

ACIFRAN

Official Name

English

acifran [INN]

Common Name

English

REDUCTOL

Brand Name

English

AY-25712

Code

English

2-FURANCARBOXYLIC ACID, 4,5-DIHYDRO-5-METHYL-4-OXO-5-PHENYL-

Systematic Name

English

AY-25,712

Code

English

(±)-4,5-DIHYDRO-5-METHYL-4-OXO-5-PHENYL-2-FUROIC ACID

Systematic Name

English

2-FURANCARBOXYLIC ACID, 4,5-DIHYDRO-5-METHYL-4-OXO-5-PHENYL-, (±)-

Common Name

English

ACIFRAN [MART.]

Common Name

English

ACIFRANUM

Common Name

English

ACIFRAN [MI]

Common Name

English

ACIFRAN [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98151