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Details

Stereochemistry ACHIRAL
Molecular Formula C10H15N5
Molecular Weight 205.26
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENFORMIN

SMILES

c1ccc(cc1)CCNC(=N)NC(=N)N

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 205.26
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
81%
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

Doses

DosePopulationAdverse events​
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
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:
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:
unhealthy
Disc. AE: Lactic acidosis...
AEs leading to
discontinuation/dose reduction:
Lactic acidosis
Sources:
AEs

AEs

AESignificanceDosePopulation
Agitation Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Anxiety Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Hypoglycemia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Hypokalemia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Increased appetite Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Lactic acidosis Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Nausea Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Polydipsia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Polyuria Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Tachycardia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Tachypnea Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
Vomiting Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
Health Status: healthy
Sex: F
Sources:
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:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing
PubMed

PubMed

TitleDatePubMed
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
2003
Effects of phenformin on the proliferation of human tumor cell lines.
2003 Dec 19
Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR.
2004 Aug
N-bromosuccinimide-fluorescein based sensitive flow-injection chemiluminescence determination of phenformin.
2004 Feb
Molecularly imprinted solid-phase extraction for the screening of antihyperglycemic biguanides.
2004 Feb 20
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.
2004 Feb 25
All-cause mortality in diabetic patients treated with combinations of sulfonylureas and biguanides.
2004 Jan-Feb
[Lactic acidosis in diabetic patient treated with metformin].
2004 Jun
A convenient five-drug cocktail for the assessment of major drug metabolizing enzymes: a pilot study.
2004 Sep
Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma.
2004 Sep 5
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
Metformin reduces adiponectin protein expression and release in 3T3-L1 adipocytes involving activation of AMP activated protein kinase.
2005 Aug 22
Contraindications can damage your health--is metformin a case in point?
2005 Dec
Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?
2005 Dec 16
Metformin transport by renal basolateral organic cation transporter hOCT2.
2005 Feb
Metabolic activation of AMP kinase in vascular smooth muscle.
2005 Jan
Effects of phentermine and phenformin on biomarkers of aging in rats.
2005 Jan-Feb
Anti-lipolytic action of AMP-activated protein kinase in rodent adipocytes.
2005 Jul 1
Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction.
2005 May 18
Acute renal ischemia rapidly activates the energy sensor AMPK but does not increase phosphorylation of eNOS-Ser1177.
2005 Nov
Identification of potential caloric restriction mimetics by microarray profiling.
2005 Nov 17
HIV/AIDS in older adults: a case report and literature review.
2005 Sep
Drug-induced pancreatitis: an update.
2005 Sep
Phenformin-induced lactic acidosis in an older diabetic patient: a recurrent drama (phenformin and lactic acidosis).
2006 Apr
LKB1, an upstream AMPK kinase, regulates glucose and lipid metabolism in cultured liver and muscle cells.
2006 Dec 22
Activators of the energy sensing kinase AMPK inhibit random cell movement and chemotaxis in U937 cells.
2006 Feb
AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3.
2006 May 28
Muscle-specific overexpression of wild type and R225Q mutant AMP-activated protein kinase gamma3-subunit differentially regulates glycogen accumulation.
2006 Sep
[Diabetic lactic acidosis].
2006 Sep 28
The phase shift hypothesis for the circadian component of winter depression.
2007
The role of mitochondria in protection of the heart by preconditioning.
2007 Aug
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
Cellular and molecular mechanisms in the long-term action of antidepressants.
2008
Comparison of gene expression changes induced by biguanides in db/db mice liver.
2008 Aug
Mechanisms of myocyte cytotoxicity induced by the multiple receptor tyrosine kinase inhibitor sunitinib.
2008 Dec
Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle.
2008 Dec
Older age and phenformin therapy: a dangerous association.
2008 Dec
[Experimental studies on hypoglycemic effects of total flavonoid from Toona sinensis].
2008 Nov
AICAR decreases the activity of two distinct amiloride-sensitive Na+-permeable channels in H441 human lung epithelial cell monolayers.
2008 Nov
Uncoupling of the LKB1-AMPKalpha energy sensor pathway by growth factors and oncogenic BRAF.
2009
AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease.
2009 Apr
Adenylate kinase and AMP signaling networks: metabolic monitoring, signal communication and body energy sensing.
2009 Apr 17
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.
2009 Apr 21
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
C-terminal phosphorylation of LKB1 is not required for regulation of AMP-activated protein kinase, BRSK1, BRSK2, or cell cycle arrest.
2009 Jan 2
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.
2009 Jul 1
Regulation of Cl(-) secretion by AMPK in vivo.
2009 Mar
Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline.
2009 May
Chemical genomics identifies the unfolded protein response as a target for selective cancer cell killing during glucose deprivation.
2009 May 15
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
Patents

Sample Use Guides

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 Sat Jun 26 11:21:03 UTC 2021
Edited
by admin
on Sat Jun 26 11:21:03 UTC 2021
Record UNII
DD5K7529CE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PHENFORMIN
HSDB   INN   MI   VANDF   WHO-DD  
INN  
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
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
WHO-ATC A10BA01
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
NCI_THESAURUS C98234
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
WHO-VATC QA10BA01
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
WHO-ATC A10BD01
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
Code System Code Type Description
INN
931
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
DRUG BANK
DB00914
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
ChEMBL
CHEMBL170988
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
WIKIPEDIA
PHENFORMIN
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
ECHA (EC/EINECS)
204-057-4
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
EVMPD
SUB09761MIG
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
DRUG CENTRAL
2126
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
FDA UNII
DD5K7529CE
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
NCI_THESAURUS
C81700
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
MESH
D010629
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
EPA CompTox
114-86-3
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
PUBCHEM
8249
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
RXCUI
8129
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY RxNorm
HSDB
3154
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
MERCK INDEX
M8615
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY Merck Index
CAS
114-86-3
Created by admin on Sat Jun 26 11:21:04 UTC 2021 , Edited by admin on Sat Jun 26 11:21:04 UTC 2021
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
SALT/SOLVATE -> PARENT
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
Related Record Type Details
METABOLITE -> PARENT
Related Record Type Details
ACTIVE MOIETY