PHENFORMIN

US Previously Marketed

First approved in 1959

Details

Stereochemistry	ACHIRAL
Molecular Formula	C10H15N5
Molecular Weight	205.2596
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC(=N)NC(=N)NCCC1=CC=CC=C1

InChI

InChIKey=ICFJFFQQTFMIBG-UHFFFAOYSA-N

InChI=1S/C10H15N5/c11-9(12)15-10(13)14-7-6-8-4-2-1-3-5-8/h1-5H,6-7H2,(H6,11,12,13,14,15)

HIDE SMILES / InChI

Description
Sources: http://www.druglib.com/activeingredient/phenformin/ | https://www.ncbi.nlm.nih.gov/pubmed/9848705 | https://www.ncbi.nlm.nih.gov/pubmed/20444419 | https://www.ncbi.nlm.nih.gov/pubmed/25511514

Phenformin is a biguanide hypoglycemic agent with actions and uses similar to those of metformin. It activates AMP-activated protein kinase (AMPK) and inhibits mTORC1 signaling. Phenformin used for the treatment of diabetes. Phenformin was removed from the U.S. market 20 years ago because of a high incidence of lactic acidosis. Risk factors for the development of lactic acidosis include renal deficiency, hepatic disease, cardiac disease, and drug interaction such as cimetidine. Phenformin exerts potential anti-neoplastic action.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
AMP-activated protein kinase, AMPK 17 Target ID: CHEMBL2096907 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964 \| https://www.ncbi.nlm.nih.gov/pubmed/14976552	Activator 1430
Monoamine oxidase A 49 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24307270	Inhibitor 8297	41.0 µM [IC50]
Sulfonylurea receptors; K-ATP channels 11 Target ID: CHEMBL2095152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20188727	Blocker 537
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20444419	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 434 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26114294	Primary	Preclinical	Unknown Approved Use Unknown
Type 2 diabetes mellitus 259 Sources: https://www.ndrugs.com/?s=phenformin http://www.druglib.com/activeingredient/phenformin/ https://www.drugs.com/international/phenformin.html	Primary	Approved 8429	INFORMIN Approved Use For the treatment of type II diabetes mellitus.
Melanoma 88 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28433543	Primary	Phase I 428	Unknown Approved Use Unknown

T_1/2

Value	Dose	Co-administered	Analyte	Population
11 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1133221/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENFORMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
81% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/1133221/	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:		PHENFORMIN plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea Vomiting Anxiety Agitation Polydipsia Polyuria Increased appetite Tachycardia Tachypnea Lactic acidosis Hypoglycemia Hypokalemia Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	Disc. AE: Lactic acidosis... AEs leading to discontinuation/dose reduction: Lactic acidosis Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic

AEs

AE	Significance	Dose	Population
Agitation	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Anxiety	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Hypoglycemia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Hypokalemia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Increased appetite	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Lactic acidosis	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Nausea	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Polydipsia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Polyuria	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Tachycardia	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Tachypnea	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Vomiting	Disc. AE	2500 mg single, oral Overdose Dose: 2500 mg Route: oral Route: single Dose: 2500 mg Sources: https://pubmed.ncbi.nlm.nih.gov/1020609	healthy n = 1 Health Status: healthy Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Lactic acidosis	Disc. AE	400 mg 2 times / day multiple, oral (max) Recommended Dose: 400 mg, 2 times / day Route: oral Route: multiple Dose: 400 mg, 2 times / day Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic	unhealthy Health Status: unhealthy Condition: Type 2 diabetes mellitus Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1217	supressor 10

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537 hOCT1 4

Drug as victim

Target	Modality	Activity
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/1293869/	yes
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26797108/	yes
hOCT1 4	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/19768675/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	supressor 10 Sources: https://pubmed.ncbi.nlm.nih.gov/23716168/

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34451	https://www.001chemical.com/chem/834-28-6
3B Scientific (Wuhan) Corp	3B2-0951	http://www.3bsc.com/index/pro_info.php?id=41856
AA Blocks	AA00ID7X	https://www.aablocks.com/goods/Goods/detail?id=AA00ID7X
AHH Chemical co.,ltd	MT-57838	http://www.ahhchemical.com/product/MT-57838.html
AK Scientific, Inc. (AKSCI)	65624	http://www.aksci.com/item_detail.php?cat=65624
Aaron Chemicals	AR00IDZP	http://www.aaronchem.com/834-28-6
AbMole Bioscience	M5336	http://www.abmole.com/products/phenformin-hcl.html
Acadechem	ACDS-067766	http://www.acadechemical.com/product/142465
Achemtek	0104-024279	http://www.achemtek.com/834-28-6
Acorn PharmaTech	ACN-048751	http://www.acornpharmatech.com/
Adooq BioScience	A10717	https://www.adooq.com/phenformin-hydrochloride.html
Alfa Chemistry	834-28-6	https://www.alfa-chemistry.com/phenformin-hydrochloride-cas-834-28-6-item-293833.htm
Ambeed	A247771	https://www.ambeed.com/products/834-28-6.html
ApexBio Technology	B1373	http://www.apexbt.com/phenformin-hcl.html
Ark Pharm	AK307682	http://www.arkpharminc.com/products/834-28-6.html
Aurora Fine Chemicals LLC	A13.140.994	http://online.aurorafinechemicals.com/info?ID=A13.140.994
Aurum Pharmatech LLC	KM2166	http://www.Aurumpharmatech.com/Product/ProductDetails/KM2166
BLD Pharm	BD147439	http://www.bldpharm.com/products/834-28-6.html
BOC Sciences	114-86-3	https://buildingblock.bocsci.com/product/n-phenethylbiguanide-cas-114-86-3-295939.html
BOC Sciences	834-28-6	https://www.bocsci.com/phenformin-hcl-cas-834-28-6-item-84-78129.html
BioChemPartner	BCP21997	http://www.biochempartner.com/834-28-6-BCP21997
BioCrick	BCC4362	http://www.biocrick.com/Phenformin-HCl-BCC4362.html
BioSynth	W-104144	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/W-104144.html
CSNpharm	CSN11690	https://www.csnpharm.com/products/phenformin-hydrochloride.html
Chem Scene	CS-1850	http://www.chemscene.com/834-28-6.html
ChemMol	30110994	http://www.chemmol.com/chemmol/30110994.html
ChemMol	49400581	http://www.chemmol.com/chemmol/49400581.html
ChemShuttle	141584	http://www.chemshuttle.com/catalogsearch/result/?q=834-28-6&cat=
Chemspace	CSSB00000014702	https://chem-space.com/CSSB00000014702
Clearsynth	CS-O-11710	https://www.clearsynth.com/en/CSO11710.html
Combi-Blocks	QA-6093	http://www.combi-blocks.com/cgi-bin/find.cgi?QA-6093
DC Chemicals	DC8990	http://www.dcchemicals.com/product_show-Phenformin_hydrochloride.html
Finetech	FT-0603518	http://www.finetechnology-ind.com/prod/detail/pub/834-28-6.html
LGC Standards	DRE-C16004500	https://www.lgcstandards.com/US/en/p/DRE-C16004500
LGC Standards	LGCFOR1574.00	https://www.lgcstandards.com/US/en/p/LGCFOR1574.00
LGC Standards	MM1574.00	https://www.lgcstandards.com/US/en/p/MM1574.00
Lab Network	LN00223478	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00223478
Matrix Scientific	157511	https://www.matrixscientific.com/157511.html
MedChem Express	HY-16397A	https://www.medchemexpress.com/phenformin-hydrochloride.html
MolPort	MolPort-000-715-918	https://www.molport.com/shop/molecule-link/MolPort-000-715-918
MolPort	MolPort-044-175-502	https://www.molport.com/shop/molecule-link/MolPort-044-175-502
Molcore	MC34451	https://www.molcore.com/product/834-28-6
MuseChem	A000869	https://www.musechem.com/product/A000869.html
OChem	4785	http://www.ocheminc.com/index.php?act=psearch&pid=34P286
Oakwood	245710	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=167560&ExtHyperLink=1
Selleck Chemicals	S2542	http://www.selleckchem.com/products/Phenformin-hydrochloride.html
Sigma-Aldrich	P7045_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/p7045?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	PHR1573_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/phr1573?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S052109	http://www.sinfoobiotech.com/product/1055507
Smolecule	S539401	http://www.smolecule.com/products/s539401
THE BioTek	bt-279431	https://www.thebiotek.com/product/inhibitors/bt-279431
VladaChem	VL272143-100G	https://www.vladachem.com/product.php?products=834-28-6
Yuhao Chemical	RT19039	http://www.chemyuhao.com/834-28-6.html
abcr GmbH	AB357549	http://www.abcr.de/shop/en/AB357549
abcr GmbH	AB376791	http://www.abcr.de/shop/en/AB376791
eNovation Chemicals	K96005	https://www.enovationchem.com/ProductDetails.asp?ProductID=K96005
iChemical	EBD40961	http://www.ichemical.com/products/834-28-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
mcule	MCULE-2649903903	https://mcule.com/MCULE-2649903903/

PubMed

Title	Date	PubMed
[Lactacidaemia and disseminated intravascular coagulation associated with phenformin medication (author's transl)].	1975 Jun 6	1140086
On the use of historical control information for trend test in carcinogenesis.	2002 Dec	12495146
N-bromosuccinimide-fluorescein based sensitive flow-injection chemiluminescence determination of phenformin.	2004 Feb	15055959
The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight.	2004 Mar 19	15044053
Phenformin and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) activation of AMP-activated protein kinase inhibits transepithelial Na+ transport across H441 lung cells.	2005 Aug 1	15919715
Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?	2005 Dec 16	16199527
Metformin transport by renal basolateral organic cation transporter hOCT2.	2005 Feb	15783073
Acute renal ischemia rapidly activates the energy sensor AMPK but does not increase phosphorylation of eNOS-Ser1177.	2005 Nov	15914772
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma3-subunit differentially regulates glycogen accumulation.	2006 Sep	16638825
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.	2007	17708636
Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.	2007 Apr	17339833
The role of mitochondria in protection of the heart by preconditioning.	2007 Aug	17631856
Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.	2007 Aug	17603555
Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry.	2007 Feb	17221919
Simultaneous determination of metformin and rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry with electrospray ionization: application to a pharmacokinetic study.	2007 Jul 1	17459785
Comparison of the kinetic characteristics of inhibitory effects exerted by biguanides and H2-blockers on human and rat organic cation transporter-mediated transport: Insight into the development of drug candidates.	2007 Jun	17614008
Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.	2007 Oct 15	17617058
Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions.	2007 Oct 28	17963526
[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].	2008 Apr	18773746
Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib.	2008 Dec	18815214
Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle.	2008 Dec	18796617
[Experimental studies on hypoglycemic effects of total flavonoid from Toona sinensis].	2008 Nov	19260289
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.	2008 Nov	18723760
Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing.	2009 Apr 17	19468337
Simultaneous determination of anti-diabetes/anti-obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS.	2009 Dec	19475544
Are animal models predictive for humans?	2009 Jan 15	19146696
Regulation of Cl(-) secretion by AMPK in vivo.	2009 Mar	18752001
Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.	2009 Sep	19502419

Patents

Sample Use Guides

In Vivo Use Guide

200-400 mg bid.

Route of Administration: Oral

In Vitro Use Guide

To evaluate the underlying mechanism of growth inhibition by phenformin, the cell cycle profile was analyzed after treating the SKOV3, Hey and IGROV-1 cell lines with varying doses (0.01-2.5 mM) of phenformin for 24 hours. Phenformin induced G0/G1 cell cycle arrest and reduced S phase in the Hey and SKOV3 OC cell lines and increased G2 phase in the IGROV-1 OC cell line in a dose-dependent manner.

Name

Type

Language

PHENFORMIN

Official Name

English

phenformin [INN]

Common Name

English

PHENFORMIN [MI]

Common Name

English

PHENFORMIN [HSDB]

Common Name

English

Phenformin [WHO-DD]

Common Name

English

IMIDODICARBONIMIDIC DIAMIDE, N-(2-PHENYLETHYL)-

Systematic Name

English

PHENFORMIN [VANDF]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QA10BD01