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
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
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 |
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 |
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 |
---|---|---|
On the use of historical control information for trend test in carcinogenesis. | 2002 Dec |
|
Response of regimens of insulin therapy in type 2 diabetes mellitus subjects with secondary failure. | 2002 May |
|
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 |
|
At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation. | 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 |
|
Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. | 2003 |
|
Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. | 2003 |
|
Involvement of organic cation transporter 1 in the lactic acidosis caused by metformin. | 2003 Apr |
|
Antidiabetic and antimalarial biguanide drugs are metal-interactive antiproteolytic agents. | 2003 Aug 15 |
|
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 |
|
Severe acidosis in a patient with type 2 diabetes mellitus, hypertension, and renal failure. | 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 |
|
All-cause mortality in diabetic patients treated with combinations of sulfonylureas and biguanides. | 2004 Jan-Feb |
|
Rapid and sensitive liquid chromatography-tandem mass spectrometric method for the quantitation of metformin in human plasma. | 2004 Sep 5 |
|
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 |
|
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 |
|
Identification of potential caloric restriction mimetics by microarray profiling. | 2005 Nov 17 |
|
Drug-induced pancreatitis: an update. | 2005 Sep |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR-gamma Agonist. | 2008 |
|
[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 |
|
[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 |
|
Crosstalk between the AMP-activated kinase and insulin signaling pathways rescues murine blastocyst cells from insulin resistance. | 2008 Sep |
|
Mechanistic insight into control of CFTR by AMPK. | 2009 Feb 27 |
|
Are animal models predictive for humans? | 2009 Jan 15 |
|
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 |
|
Mood, side-effects and smoking outcomes among persons with and without probable lifetime depression taking varenicline. | 2009 May |
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
Fri Dec 15 17:13:45 GMT 2023
by
admin
on
Fri Dec 15 17:13:45 GMT 2023
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Record UNII |
91XC93EU03
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Record Status |
Validated (UNII)
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Record Version |
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-
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C98234
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