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Details

Stereochemistry ACHIRAL
Molecular Formula C10H15N5.ClH
Molecular Weight 241.7209
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENFORMIN HYDROCHLORIDE

SMILES

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

InChI

InChIKey=YSUCWSWKRIOILX-UHFFFAOYSA-N
InChI=1S/C10H15N5.ClH/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);1H

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

Molecular Formula ClH
Molecular Weight 36.4609
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
n = 1
Health Status: healthy
Sex: F
Population Size: 1
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 (max)
Recommended
Dose: 400 mg, 2 times / day
Route: oral
Route: multiple
Dose: 400 mg, 2 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
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
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Anxiety Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Hypoglycemia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Hypokalemia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Increased appetite Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Lactic acidosis Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Nausea Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Polydipsia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Polyuria Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Tachycardia Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Tachypnea Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
Vomiting Disc. AE
2500 mg single, oral
Overdose
Dose: 2500 mg
Route: oral
Route: single
Dose: 2500 mg
Sources:
healthy
n = 1
Health Status: healthy
Sex: F
Population Size: 1
Sources:
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:
unhealthy
Health Status: unhealthy
Condition: Type 2 diabetes mellitus
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Enhanced secretion of glucagon-like peptide 1 by biguanide compounds.
2002 Nov 15
A new method for determination of buformin in plasma and urine by ion-paired reversed-phase HPLC with ultraviolet detection.
2002 Oct
[Adverse effect of biguanides].
2002 Sep
Sustaining pattern of phenformin hydrochloride using various polymers and waxes.
2002 Sep-Oct
Insulin and longevity: antidiabetic biguanides as geroprotectors.
2003
Effects of phenformin on the proliferation of human tumor cell lines.
2003 Dec 19
Should we screen diabetic patients using biguanides for megaloblastic anaemia?
2003 May
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis.
2003 Nov 24
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
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
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
Use of microarray biomarkers to identify longevity therapeutics.
2006 Feb
Activators of the energy sensing kinase AMPK inhibit random cell movement and chemotaxis in U937 cells.
2006 Feb
[Traditional contraindications to the use of metformin -- more harmful than beneficial?].
2006 Jan 20
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
2006 Jan 25
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
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae.
2007
The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells.
2007 Apr 6
The role of mitochondria in protection of the heart by preconditioning.
2007 Aug
Pharmacological activators of AMP-activated protein kinase have different effects on Na+ transport processes across human lung epithelial cells.
2007 Aug
Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration.
2007 Jul
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
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
Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.
2007 Oct 15
[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].
2008 Apr
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
Biguanide-induced mitochondrial dysfunction yields increased lactate production and cytotoxicity of aerobically-poised HepG2 cells and human hepatocytes in vitro.
2008 Dec 1
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice.
2008 Jun 1
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
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.
2009 Apr 21
Mechanistic insight into control of CFTR by AMPK.
2009 Feb 27
Are animal models predictive for humans?
2009 Jan 15
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 Fri Jun 25 23:14:48 UTC 2021
Edited
by admin
on Fri Jun 25 23:14:48 UTC 2021
Record UNII
91XC93EU03
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
PHENFORMIN HYDROCHLORIDE
MART.   MI   WHO-DD  
Common Name English
PHENFORMIN HYDROCHLORIDE [MI]
Common Name English
IMIDODICARBONIMIDIC DIAMIDE, N-(2-PHENYLETHYL)-, MONOHYDROCHLORIDE
Common Name English
DEBEI
Brand Name English
NSC-23100
Code English
PHENFORMIN HYDROCHLORIDE [WHO-DD]
Common Name English
PHENFORMIN HYDROCHLORIDE [MART.]
Common Name English
PHENFORMIN HCL
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C98234
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
Code System Code Type Description
MERCK INDEX
M8615
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY Merck Index
RXCUI
235288
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY RxNorm
NCI_THESAURUS
C81696
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
EVMPD
SUB03743MIG
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
ECHA (EC/EINECS)
212-637-3
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
PUBCHEM
13266
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
EPA CompTox
834-28-6
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
DRUG BANK
DBSALT000273
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
CAS
834-28-6
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
FDA UNII
91XC93EU03
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
ChEMBL
CHEMBL170988
Created by admin on Fri Jun 25 23:14:48 UTC 2021 , Edited by admin on Fri Jun 25 23:14:48 UTC 2021
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY