This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Ciglitazone
Accession Number
DB09201
Type
Small Molecule
Groups
Experimental
Description

Ciglitazone (INN) is a thiazolidinedione. Developed by Takeda Pharmaceuticals in the early 1980s, it is considered the prototypical compound for the thiazolidinedione class.

Ciglitazone was never used as a medication, but it sparked interest in the effects of thiazolidinediones. Several analogues were later developed, some of which—such as pioglitazone and troglitazone—made it to the market.

Ciglitazone significantly decreases VEGF production by human granulosa cells in an in vitro study, and may potentially be used in ovarian hyperstimulation syndrome. Ciglitazone is a potent and selective PPARγ ligand. It binds to the PPARγ ligand-binding domain with an EC50 of 3.0 µM. Ciglitazone is active in vivo as an anti-hyperglycemic agent in the ob/ob murine model. Inhibits HUVEC differentiation and angiogenesis and also stimulates adipogenesis and decreases osteoblastogenesis in human mesenchymal stem cells.

Structure
Thumb
Synonyms
  • ciglitazona
Categories
UNII
U8QXS1WU8G
CAS number
74772-77-3
Weight
Average: 333.45
Monoisotopic: 333.139864779
Chemical Formula
C18H23NO3S
InChI Key
YZFWTZACSRHJQD-UHFFFAOYSA-N
InChI
InChI=1S/C18H23NO3S/c1-18(9-3-2-4-10-18)12-22-14-7-5-13(6-8-14)11-15-16(20)19-17(21)23-15/h5-8,15H,2-4,9-12H2,1H3,(H,19,20,21)
IUPAC Name
5-({4-[(1-methylcyclohexyl)methoxy]phenyl}methyl)-1,3-thiazolidine-2,4-dione
SMILES
CC1(COC2=CC=C(CC3SC(=O)NC3=O)C=C2)CCCCC1

Pharmacology

Indication
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UPeroxisome proliferator-activated receptor gammaNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Ciglitazone can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Ciglitazone.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Ciglitazone is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Ciglitazone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ciglitazone.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Ciglitazone can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of Ciglitazone can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Ciglitazone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Ciglitazone.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Ciglitazone.
Food Interactions
Not Available

References

General References
  1. Pershadsingh HA, Szollosi J, Benson S, Hyun WC, Feuerstein BG, Kurtz TW: Effects of ciglitazone on blood pressure and intracellular calcium metabolism. Hypertension. 1993 Jun;21(6 Pt 2):1020-3. [PubMed:8505086]
  2. Imoto H, Imamiya E, Momose Y, Sugiyama Y, Kimura H, Sohda T: Studies on non-thiazolidinedione antidiabetic agents. 1. Discovery of novel oxyiminoacetic acid derivatives. Chem Pharm Bull (Tokyo). 2002 Oct;50(10):1349-57. [PubMed:12372861]
  3. Sohda T, Kawamatsu Y, Fujita T, Meguro K, Ikeda H: [Discovery and development of a new insulin sensitizing agent, pioglitazone]. Yakugaku Zasshi. 2002 Nov;122(11):909-18. [PubMed:12440149]
  4. Shah DK, Menon KM, Cabrera LM, Vahratian A, Kavoussi SK, Lebovic DI: Thiazolidinediones decrease vascular endothelial growth factor (VEGF) production by human luteinized granulosa cells in vitro. Fertil Steril. 2010 Apr;93(6):2042-7. doi: 10.1016/j.fertnstert.2009.02.059. Epub 2009 Apr 1. [PubMed:19342033]
  5. Xin X, Yang S, Kowalski J, Gerritsen ME: Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo. J Biol Chem. 1999 Mar 26;274(13):9116-21. [PubMed:10085162]
External Links
KEGG Drug
D03493
PubChem Compound
2750
PubChem Substance
310265109
ChemSpider
2648
ChEBI
64227
ChEMBL
CHEMBL7002
Wikipedia
Ciglitazone

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00534 mg/mLALOGPS
logP3.93ALOGPS
logP4.28ChemAxon
logS-4.8ALOGPS
pKa (Strongest Acidic)6.61ChemAxon
pKa (Strongest Basic)-4.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.4 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity91.26 m3·mol-1ChemAxon
Polarizability36.36 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Not Available
Direct Parent
Phenol ethers
Alternative Parents
Phenoxy compounds / Thiazolidinediones / Alkyl aryl ethers / Dicarboximides / Thiocarbamic acid derivatives / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides
show 2 more
Substituents
Phenoxy compound / Phenol ether / Alkyl aryl ether / Thiazolidinedione / Monocyclic benzene moiety / Dicarboximide / Thiazolidine / Thiocarbamic acid derivative / Carbonic acid derivative / Organoheterocyclic compound
show 12 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
aromatic ether, thiazolidinone (CHEBI:64227)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Wick M, Hurteau G, Dessev C, Chan D, Geraci MW, Winn RA, Heasley LE, Nemenoff RA: Peroxisome proliferator-activated receptor-gamma is a target of nonsteroidal anti-inflammatory drugs mediating cyclooxygenase-independent inhibition of lung cancer cell growth. Mol Pharmacol. 2002 Nov;62(5):1207-14. [PubMed:12391285]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Jaakkola T, Backman JT, Neuvonen M, Neuvonen PJ: Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14. doi: 10.1016/j.clpt.2004.12.266. [PubMed:15900286]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Jaakkola T, Backman JT, Neuvonen M, Neuvonen PJ: Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther. 2005 May;77(5):404-14. doi: 10.1016/j.clpt.2004.12.266. [PubMed:15900286]

Drug created on October 16, 2015 16:20 / Updated on November 02, 2018 07:00