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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 of PHENFORMIN

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

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
[Lactacidaemia and disseminated intravascular coagulation associated with phenformin medication (author's transl)].
1975 Jun 6
Phenformin as a cause of primary pulmonary hypertension.
1976 Dec 11
Lactic acidosis update for critical care clinicians.
2001 Feb
[Concentration of thyrotropic hormone and free thyroxin in children with Down's syndrome].
2001 Jun
[Recommendations for perioperative interruption of metformin medication].
2001 Oct 26
Parasitic infections of the gastrointestinal tract.
2001 Sep
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
2002
Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin.
2002 Aug
Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with secondary failure.
2002 May
Phenformin suppresses calcium responses to glutamate and protects hippocampal neurons against excitotoxicity.
2002 May
A new method for determination of buformin in plasma and urine by ion-paired reversed-phase HPLC with ultraviolet detection.
2002 Oct
Sustaining pattern of phenformin hydrochloride using various polymers and waxes.
2002 Sep-Oct
Insulin and longevity: antidiabetic biguanides as geroprotectors.
2003
[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
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.
2003
Severe acidosis in a patient with type 2 diabetes mellitus, hypertension, and renal failure.
2003 May
Molecularly imprinted solid-phase extraction for the screening of antihyperglycemic biguanides.
2004 Feb 20
[Lactic acidosis in diabetic patient treated with metformin].
2004 Jun
The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight.
2004 Mar 19
Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma.
2004 Sep 5
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
Effects of phentermine and phenformin on biomarkers of aging in rats.
2005 Jan-Feb
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
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
Solid phase extraction--non-aqueous capillary electrophoresis for determination of metformin, phenformin and glyburide in human plasma.
2006 Oct 20
The role of AMPK and mTOR in nutrient sensing in pancreatic beta-cells.
2007 Apr 6
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
Older age and phenformin therapy: a dangerous association.
2008 Dec
Hazards posed by a banned drug--phenformin is still hanging around.
2008 Feb
Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice.
2008 Jun 1
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance.
2008 Sep
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
Regulation of Cl(-) secretion by AMPK in vivo.
2009 Mar
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 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
  • 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 Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
WHO-ATC A10BA01
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
NCI_THESAURUS C98234
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
WHO-VATC QA10BA01
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
WHO-ATC A10BD01
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
Code System Code Type Description
INN
931
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
DRUG BANK
DB00914
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
ChEMBL
CHEMBL170988
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
WIKIPEDIA
PHENFORMIN
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
ECHA (EC/EINECS)
204-057-4
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
EVMPD
SUB09761MIG
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
DRUG CENTRAL
2126
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
FDA UNII
DD5K7529CE
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
NCI_THESAURUS
C81700
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
SMS_ID
100000082253
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
MESH
D010629
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
CHEBI
8064
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
EPA CompTox
DTXSID1023449
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
PUBCHEM
8249
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
RXCUI
8129
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY RxNorm
HSDB
3154
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
MERCK INDEX
m8615
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY Merck Index
CAS
114-86-3
Created by admin on Fri Dec 15 15:09:52 GMT 2023 , Edited by admin on Fri Dec 15 15:09:52 GMT 2023
PRIMARY
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TRANSPORTER -> INHIBITOR
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TRANSPORTER -> INHIBITOR
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METABOLITE -> PARENT
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ACTIVE MOIETY