Ertiprotafib

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

Identification

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Name
Ertiprotafib
Accession Number
DB06521
Type
Small Molecule
Groups
Investigational
Description

Ertiprotafib belongs to a novel class of insulin sensitizers developed for treatment of type 2 diabetes. In insulin-resistant rodent models, ertiprotafib and a close analog lowered both fasting blood glucose and insulin levels and improved glycemic excursion during an oral glucose tolerance test.

Structure
Thumb
Synonyms
Not Available
External IDs
PTP-112
Categories
UNII
5TPM2EB426
CAS number
251303-04-5
Weight
Average: 559.52
Monoisotopic: 558.086429
Chemical Formula
C31H27BrO3S
InChI Key
FONCZICQWCUXEB-RUZDIDTESA-N
InChI
InChI=1S/C31H27BrO3S/c1-17-14-22(15-18(2)29(17)35-25(31(33)34)16-21-10-6-5-7-11-21)27-23-12-8-9-13-24(23)28(32)30-26(27)19(3)20(4)36-30/h5-15,25H,16H2,1-4H3,(H,33,34)/t25-/m1/s1
IUPAC Name
(2R)-2-(4-{9-bromo-2,3-dimethylnaphtho[2,3-b]thiophen-4-yl}-2,6-dimethylphenoxy)-3-phenylpropanoic acid
SMILES
CC1=C(C)C2=C(C3=CC(C)=C(O[C@H](CC4=CC=CC=C4)C(O)=O)C(C)=C3)C3=CC=CC=C3C(Br)=C2S1

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

Pharmacodynamics
Not Available
Mechanism of action

The complete mechanism of action for ertiprotafib and related compounds in vivo may involve multiple independent mechanisms, including (but not necessarily limited to) PTP1b inhibition and dual PPARalpha/PPARgamma agonism.

TargetActionsOrganism
UTyrosine-protein phosphatase non-receptor type 1Not AvailableHumans
UInhibitor of nuclear factor kappa-B kinase subunit betaNot AvailableHumans
UPeroxisome proliferator-activated receptor alphaNot AvailableHumans
UPeroxisome proliferator-activated receptor gammaNot AvailableHumans
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
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
138230
BindingDB
50209683
ChEMBL
CHEMBL184041

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 Solubility3.29e-05 mg/mLALOGPS
logP7.95ALOGPS
logP9.99ChemAxon
logS-7.2ALOGPS
pKa (Strongest Acidic)4.31ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area46.53 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity150.45 m3·mol-1ChemAxon
Polarizability57.48 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
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 naphthothiophenes. These are compounds containing a naphthalene (or a derivative) fused to thiophene.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Naphthothiophenes
Direct Parent
Naphthothiophenes
Alternative Parents
Phenylpropanoic acids / Phenoxyacetic acid derivatives / 1-benzothiophenes / m-Xylenes / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Aryl bromides / Thiophenes / Heteroaromatic compounds
show 6 more
Substituents
Naphthothiophene / Phenoxyacetate / 3-phenylpropanoic-acid / Benzothiophene / 1-benzothiophene / Phenoxy compound / Phenol ether / M-xylene / Xylene / Alkyl aryl ether
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EI...
Gene Name
PTPN1
Uniprot ID
P18031
Uniprot Name
Tyrosine-protein phosphatase non-receptor type 1
Molecular Weight
49966.44 Da
References
  1. Shrestha S, Bhattarai BR, Cho H, Choi JK, Cho H: PTP1B inhibitor Ertiprotafib is also a potent inhibitor of IkappaB kinase beta (IKK-beta). Bioorg Med Chem Lett. 2007 May 15;17(10):2728-30. Epub 2007 Mar 3. [PubMed:17407812]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Scaffold protein binding
Specific Function
Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or oth...
Gene Name
IKBKB
Uniprot ID
O14920
Uniprot Name
Inhibitor of nuclear factor kappa-B kinase subunit beta
Molecular Weight
86563.245 Da
References
  1. Shrestha S, Bhattarai BR, Cho H, Choi JK, Cho H: PTP1B inhibitor Ertiprotafib is also a potent inhibitor of IkappaB kinase beta (IKK-beta). Bioorg Med Chem Lett. 2007 May 15;17(10):2728-30. Epub 2007 Mar 3. [PubMed:17407812]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Erbe DV, Wang S, Zhang YL, Harding K, Kung L, Tam M, Stolz L, Xing Y, Furey S, Qadri A, Klaman LD, Tobin JF: Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms. Mol Pharmacol. 2005 Jan;67(1):69-77. Epub 2004 Oct 8. [PubMed:15475571]
Kind
Protein
Organism
Humans
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. Erbe DV, Wang S, Zhang YL, Harding K, Kung L, Tam M, Stolz L, Xing Y, Furey S, Qadri A, Klaman LD, Tobin JF: Ertiprotafib improves glycemic control and lowers lipids via multiple mechanisms. Mol Pharmacol. 2005 Jan;67(1):69-77. Epub 2004 Oct 8. [PubMed:15475571]

Drug created on March 19, 2008 10:35 / Updated on June 04, 2019 06:25