U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C10H15N5.ClH
Molecular Weight 241.721
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PHENFORMIN HYDROCHLORIDE

SMILES

Cl.NC(=N)NC(=N)NCCC1=CC=CC=C1

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 ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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
Parasitic infections of the gastrointestinal tract.
2001 Sep
Involvement of organic cation transporter 1 in hepatic and intestinal distribution of metformin.
2002 Aug
Enhanced secretion of glucagon-like peptide 1 by biguanide compounds.
2002 Nov 15
Sustaining pattern of phenformin hydrochloride using various polymers and waxes.
2002 Sep-Oct
At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation.
2003
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus: systematic review and meta-analysis.
2003 Nov 24
N-bromosuccinimide-fluorescein based sensitive flow-injection chemiluminescence determination of phenformin.
2004 Feb
LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1.
2004 Feb 25
The combination of metformin and a dipeptidyl peptidase IV inhibitor prevents 5-fluorouracil-induced reduction of small intestine weight.
2004 Mar 19
A convenient five-drug cocktail for the assessment of major drug metabolizing enzymes: a pilot study.
2004 Sep
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
Does AMP-activated protein kinase couple inhibition of mitochondrial oxidative phosphorylation by hypoxia to calcium signaling in O2-sensing cells?
2005 Dec 16
Effects of phentermine and phenformin on biomarkers of aging in rats.
2005 Jan-Feb
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
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
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
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
Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer.
2007 Apr
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
Simultaneous determination of metformin and glipizide in human plasma by liquid chromatography-tandem mass spectrometry.
2007 Feb
Protein kinase CK2 acts as a signal molecule switching between the NDPK-A/AMPK alpha1 complex and NDPK-B.
2007 Jan
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 the atherogenic properties of vascular smooth muscle proteoglycans by oral anti-hyperglycemic agents.
2007 Mar-Apr
Regulation of multisite phosphorylation and 14-3-3 binding of AS160 in response to IGF-1, EGF, PMA and AICAR.
2007 Oct 15
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
[Cardiovascular risk and cardiometabolic risk: an epidemiological evaluation].
2008 Apr
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
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance.
2008 Sep
High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus.
2009 Apr 21
Quasi-equilibrium analysis of the ion-pair mediated membrane transport of low-permeability drugs.
2009 Jul 1
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 Thu Jul 06 00:35:32 UTC 2023
Edited
by admin
on Thu Jul 06 00:35:32 UTC 2023
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 Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
Code System Code Type Description
MERCK INDEX
M8615
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY Merck Index
RXCUI
235288
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY RxNorm
NCI_THESAURUS
C81696
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
EVMPD
SUB03743MIG
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
SMS_ID
100000085681
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
ECHA (EC/EINECS)
212-637-3
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
PUBCHEM
13266
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
EPA CompTox
DTXSID0021121
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
DRUG BANK
DBSALT000273
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
NSC
23100
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
CAS
834-28-6
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
FDA UNII
91XC93EU03
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
ChEMBL
CHEMBL170988
Created by admin on Thu Jul 06 00:35:32 UTC 2023 , Edited by admin on Thu Jul 06 00:35:32 UTC 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY