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

Molecular Formula	C10H15N5
Molecular Weight	205.2596
Charge	0
Count

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

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 1447
Monoamine oxidase A 52 Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24307270	Inhibitor 8504	41.0 µM [IC50]
Sulfonylurea receptors; K-ATP channels 11 Target ID: CHEMBL2095152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20188727	Blocker 555
Mammalian target of Rapamycin (mTORC1) 23 Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20444419	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Ovarian cancer 160 Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964	Primary	Preclinical	Unknown Approved Use Unknown
Breast cancer 432 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26114294	Primary	Preclinical	Unknown Approved Use Unknown
Type 2 diabetes mellitus 262 Sources: https://www.ndrugs.com/?s=phenformin http://www.druglib.com/activeingredient/phenformin/ https://www.drugs.com/international/phenformin.html	Primary	Approved 8583	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 438	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 Health Status: healthy Sex: F 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 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 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F 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 Health Status: healthy Sex: F Sources: https://pubmed.ncbi.nlm.nih.gov/1020609
Lactic acidosis	Disc. AE	400 mg 2 times / day multiple, oral 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 Sources: https://www.mims.com/philippines/drug/info/phenformin?mtype=generic

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
		substrate 1388	supressor 10

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 2052 hOCT1 4

Drug as victim

Target	Modality	Activity
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/1293869/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/26797108/	yes
hOCT1 4	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/19768675/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	supressor 11 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
Aaron Chemicals	AR00IDZP	http://www.aaronchem.com/834-28-6
abcr GmbH	AB357549	http://www.abcr.de/shop/en/AB357549
abcr GmbH	AB376791	http://www.abcr.de/shop/en/AB376791
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
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
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
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
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
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
CSNpharm	CSN11690	https://www.csnpharm.com/products/phenformin-hydrochloride.html
DC Chemicals	DC8990	http://www.dcchemicals.com/product_show-Phenformin_hydrochloride.html
eNovation Chemicals	K96005	https://www.enovationchem.com/ProductDetails.asp?ProductID=K96005
Finetech	FT-0603518	http://www.finetechnology-ind.com/prod/detail/pub/834-28-6.html
iChemical	EBD40961	http://www.ichemical.com/products/834-28-6.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs
Lab Network	LN00223478	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00223478
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
Matrix Scientific	157511	https://www.matrixscientific.com/157511.html
mcule	MCULE-2649903903	https://mcule.com/MCULE-2649903903/
MedChem Express	HY-16397A	https://www.medchemexpress.com/phenformin-hydrochloride.html
Molcore	MC34451	https://www.molcore.com/product/834-28-6
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
MuseChem	A000869	https://www.musechem.com/product/A000869.html
Oakwood	245710	http://www.oakwoodchemical.com/ProductsList.aspx?CategoryID=-2&txtSearch=167560&ExtHyperLink=1
OChem	4785	http://www.ocheminc.com/index.php?act=psearch&pid=34P286
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

PubMed

Title	Date	PubMed
Simultaneous determination of anti-diabetes/anti-obesity drugs by LC/PDA, and targeted analysis of sibutramine analog in dietary supplements by LC/MS/MS.	2009-12	19475544
Activation of AMP-activated protein kinase by interleukin-6 in rat skeletal muscle: association with changes in cAMP, energy state, and endogenous fuel mobilization.	2009-09	19502419
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.	2009-07-01	19264104
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.	2009-05-15	19435925
Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline.	2009-05	19238488
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.	2009-04-21	19349317
Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing.	2009-04-17	19468337
AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease.	2009-04	19275766
Regulation of Cl(-) secretion by AMPK in vivo.	2009-03	18752001
Mechanistic insight into control of CFTR by AMPK.	2009-02-27	19095655
Are animal models predictive for humans?	2009-01-15	19146696
C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest.	2009-01-02	18854318
Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF.	2009	19274086
Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro.	2008-12-01	18817800
Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib.	2008-12	18815214
Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle.	2008-12	18796617
Older age and phenformin therapy: a dangerous association.	2008-12	18415028
[Experimental studies on hypoglycemic effects of total flavonoid from Toona sinensis].	2008-11	19260289
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.	2008-11	18723760
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance.	2008-09	18577554
Comparison of gene expression changes induced by biguanides in db/db mice liver.	2008-08	18670165
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice.	2008-06-01	18387000
[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].	2008-04	18773746
Hazards posed by a banned drug--phenformin is still hanging around.	2008-02	18239244
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators.	2008-01-15	17995453
Cellular and molecular mechanisms in the long-term action of antidepressants.	2008	19170396
Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR-gamma Agonist.	2008	18815616
Anti-proliferative activity of oral anti-hyperglycemic agents on human vascular smooth muscle cells: thiazolidinediones (glitazones) have enhanced activity under high glucose conditions.	2007-10-28	17963526
Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.	2007-10-15	17617058
The role of mitochondria in protection of the heart by preconditioning.	2007-08	17631856
Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.	2007-08	17603555
Simultaneous determination of metformin and rosiglitazone in human plasma by liquid chromatography/tandem mass spectrometry with electrospray ionization: application to a pharmacokinetic study.	2007-07-01	17459785
Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.	2007-07	17369473
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.	2007-06	17614008
The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells.	2007-04-06	17287212
Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.	2007-04	17339833
Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry.	2007-02	17221919
Protein kinase CK2 acts as a signal molecule switching between the NDPK-A/AMPK alpha1 complex and NDPK-B.	2007-01	17135357
The phase shift hypothesis for the circadian component of winter depression.	2007	17969866
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.	2007	17708636
LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.	2006-12-22	17083919
Solid phase extraction--non-aqueous capillary electrophoresis for determination of metformin, phenformin and glyburide in human plasma.	2006-10-20	16787767
[Diabetic lactic acidosis].	2006-09-28	17022521
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma3-subunit differentially regulates glycogen accumulation.	2006-09	16638825
Phosphorylation and 14-3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose.	2006-07	16771775
AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3.	2006-05-28	16620785
Phenformin-induced lactic acidosis in an older diabetic patient: a recurrent drama (phenformin and lactic acidosis).	2006-04	16567854
Use of microarray biomarkers to identify longevity therapeutics.	2006-02	16441842
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.	2006-01-25	16437448
Regulation of the atherogenic properties of vascular smooth muscle proteoglycans by oral anti-hyperglycemic agents.	2005-07-12	17331859

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.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 17:48:39 GMT 2025` Edited by `admin` on `Mon Mar 31 17:48:39 GMT 2025`
Record UNII	DD5K7529CE
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

PHENFORMIN

Official Name

English

PHENFORMIN [HSDB]

Preferred Name

English

phenformin [INN]

Common Name

English

PHENFORMIN [MI]

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