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 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
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.	2002	12076461
Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin.	2002 Aug	12130709
On the use of historical control information for trend test in carcinogenesis.	2002 Dec	12495146
Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with secondary failure.	2002 May	12186116
Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity.	2002 May	12009768
Enhanced secretion of glucagon-like peptide 1 by biguanide compounds.	2002 Nov 15	12419322
A new method for determination of buformin in plasma and urine by ion-paired reversed-phase HPLC with ultraviolet detection.	2002 Oct	12378556
[Adverse effect of biguanides].	2002 Sep	12387023
Sustaining pattern of phenformin hydrochloride using various polymers and waxes.	2002 Sep-Oct	12481378
Insulin and longevity: antidiabetic biguanides as geroprotectors.	2003	14618027
At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation.	2003	14575531
[A 50-year history of new drugs in Japan-the development and progress of anti-diabetic drugs and the epidemiological aspects of diabetes mellitus].	2003	14570054
Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade.	2003	14511394
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.	2003	12804446
Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin.	2003 Apr	12644585
Antidiabetic and antimalarial biguanide drugs are metal-interactive antiproteolytic agents.	2003 Aug 15	12906931
Should we screen diabetic patients using biguanides for megaloblastic anaemia?	2003 May	12772378
Severe acidosis in a patient with type 2 diabetes mellitus, hypertension, and renal failure.	2003 May	12740293
N-bromosuccinimide-fluorescein based sensitive flow-injection chemiluminescence determination of phenformin.	2004 Feb	15055959
Molecularly imprinted solid-phase extraction for the screening of antihyperglycemic biguanides.	2004 Feb 20	14971497
[Lactic acidosis in diabetic patient treated with metformin].	2004 Jun	15283644
The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight.	2004 Mar 19	15044053
A convenient five-drug cocktail for the assessment of major drug metabolizing enzymes: a pilot study.	2004 Sep	15327588
Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma.	2004 Sep 5	15261814
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
Contraindications can damage your health--is metformin a case in point?	2005 Dec	16283245
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
Effects of phentermine and phenformin on biomarkers of aging in rats.	2005 Jan-Feb	15591752
Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes.	2005 Jul 1	15878856
Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction.	2005 May 18	15889149
Acute renal ischemia rapidly activates the energy sensor AMPK but does not increase phosphorylation of eNOS-Ser1177.	2005 Nov	15914772
Identification of potential caloric restriction mimetics by microarray profiling.	2005 Nov 17	16189280
HIV/AIDS in older adults: a case report and literature review.	2005 Sep	16153142
Drug-induced pancreatitis: an update.	2005 Sep	16082282
[Traditional contraindications to the use of metformin -- more harmful than beneficial?].	2006 Jan 20	16418951
Solid phase extraction--non-aqueous capillary electrophoresis for determination of metformin, phenformin and glyburide in human plasma.	2006 Oct 20	16787767
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma3-subunit differentially regulates glycogen accumulation.	2006 Sep	16638825
[Diabetic lactic acidosis].	2006 Sep 28	17022521
The phase shift hypothesis for the circadian component of winter depression.	2007	17969866
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.	2007	17708636
Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.	2007 Jul	17369473
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
Cellular and molecular mechanisms in the long-term action of antidepressants.	2008	19170396
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators.	2008 Jan 15	17995453
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
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.	2009 Apr 21	19349317
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
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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:09:52 GMT 2023` Edited by `admin` on `Fri Dec 15 15:09:52 GMT 2023`
Record UNII	DD5K7529CE
Record Status	`Validated (UNII)`
Record Version

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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