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
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)
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.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2096907 |
|||
Target ID: CHEMBL1951 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24307270 |
41.0 µM [IC50] | ||
Target ID: CHEMBL2095152 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20188727 |
|||
Target ID: CHEMBL2221341 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20444419 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
|||
Primary | Unknown Approved UseUnknown |
|||
Primary | INFORMIN Approved UseFor the treatment of type II diabetes mellitus. |
|||
Primary | Unknown Approved UseUnknown |
T1/2
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 |
Funbound
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 |
healthy n = 1 |
Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea Sources: Vomiting Anxiety Agitation Polydipsia Polyuria Increased appetite Tachycardia Tachypnea Lactic acidosis Hypoglycemia Hypokalemia |
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
AE | Significance | Dose | Population |
---|---|---|---|
Agitation | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Anxiety | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Hypoglycemia | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Hypokalemia | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Increased appetite | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Lactic acidosis | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Nausea | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Polydipsia | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Polyuria | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Tachycardia | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Tachypnea | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
Vomiting | Disc. AE | 2500 mg single, oral Overdose |
healthy n = 1 |
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
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/23716168/ |
PubMed
Title | Date | PubMed |
---|---|---|
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 |
|
[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 |
|
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 |
|
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 |
|
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 |
|
Phosphorylation and 14-3-3 binding of Arabidopsis trehalose-phosphate synthase 5 in response to 2-deoxyglucose. | 2006 Jul |
|
AMP-activated protein kinase (AMPK) activating agents cause dephosphorylation of Akt and glycogen synthase kinase-3. | 2006 May 28 |
|
Solid phase extraction--non-aqueous capillary electrophoresis for determination of metformin, phenformin and glyburide in human plasma. | 2006 Oct 20 |
|
[Diabetic lactic acidosis]. | 2006 Sep 28 |
|
Pharmacological studies on anti-hyperglycemic effect of folium eriobotryae. | 2007 |
|
Methyl succinate antagonises biguanide-induced AMPK-activation and death of pancreatic beta-cells through restoration of mitochondrial electron transfer. | 2007 Apr |
|
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 |
|
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 |
|
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 |
|
Hazards posed by a banned drug--phenformin is still hanging around. | 2008 Feb |
|
Complementary regulation of TBC1D1 and AS160 by growth factors, insulin and AMPK activators. | 2008 Jan 15 |
|
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 |
|
Mechanistic insight into control of CFTR by AMPK. | 2009 Feb 27 |
|
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/29245964
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
Edited
Wed Jul 05 22:41:37 UTC 2023
by
admin
on
Wed Jul 05 22:41:37 UTC 2023
|
Record UNII |
DD5K7529CE
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
WHO-VATC |
QA10BD01
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
||
|
WHO-ATC |
A10BA01
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
||
|
NCI_THESAURUS |
C98234
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
||
|
WHO-VATC |
QA10BA01
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
||
|
WHO-ATC |
A10BD01
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
931
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
DB00914
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
CHEMBL170988
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
PHENFORMIN
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
204-057-4
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
SUB09761MIG
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
2126
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
DD5K7529CE
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
C81700
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
100000082253
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
D010629
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
8064
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
DTXSID1023449
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
8249
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
8129
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | RxNorm | ||
|
3154
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | |||
|
M8615
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
PRIMARY | Merck Index | ||
|
114-86-3
Created by
admin on Wed Jul 05 22:41:37 UTC 2023 , Edited by admin on Wed Jul 05 22:41:37 UTC 2023
|
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 |