Identification

Name
T131
Accession Number
DB05490
Type
Small Molecule
Groups
Investigational
Description

T131, an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia.

Structure
Thumb
Synonyms
  • INT-131
External IDs
AMG-131
Categories
UNII
E7ILQ6U50J
CAS number
Not Available
Weight
Average: 1974.365
Monoisotopic: 1973.046477216
Chemical Formula
C86H140N32O18S2
InChI Key
UVXNDFHXUYTRBE-AHMHAWCVSA-N
InChI
InChI=1S/C86H140N32O18S2/c87-34-4-1-14-55-71(125)111-60(16-3-6-36-89)80(134)118-42-12-21-67(118)79(133)115-64(45-50-26-32-53(121)33-27-50)75(129)110-59(19-10-40-104-85(97)98)70(124)108-56(15-2-5-35-88)73(127)116-65(77(131)112-61(81(135)136)20-11-41-105-86(99)100)46-137-138-47-66(78(132)114-62(43-48-22-28-51(119)29-23-48)74(128)109-58(69(123)107-55)18-9-39-103-84(95)96)117-76(130)63(44-49-24-30-52(120)31-25-49)113-72(126)57(17-8-38-102-83(93)94)106-68(122)54(90)13-7-37-101-82(91)92/h22-33,54-67,119-121H,1-21,34-47,87-90H2,(H,106,122)(H,107,123)(H,108,124)(H,109,128)(H,110,129)(H,111,125)(H,112,131)(H,113,126)(H,114,132)(H,115,133)(H,116,127)(H,117,130)(H,135,136)(H4,91,92,101)(H4,93,94,102)(H4,95,96,103)(H4,97,98,104)(H4,99,100,105)/t54-,55-,56-,57-,58-,59-,60+,61-,62-,63-,64-,65-,66-,67-/m0/s1
IUPAC Name
(2S)-2-{[(3S,6S,9S,12R,17R,20S,23S,26S,29R,34aS)-17-[(2S)-2-[(2S)-2-[(2S)-2-amino-5-carbamimidamidopentanamido]-5-carbamimidamidopentanamido]-3-(4-hydroxyphenyl)propanamido]-9,26,29-tris(4-aminobutyl)-6,23-bis(3-carbamimidamidopropyl)-3,20-bis[(4-hydroxyphenyl)methyl]-1,4,7,10,18,21,24,27,30-nonaoxo-dotriacontahydropyrrolo[2,1-p]1,2-dithia-5,8,11,14,17,20,23,26,29-nonaazacyclodotriacontan-12-yl]formamido}-5-carbamimidamidopentanoic acid
SMILES
[H][[email protected]@]12CCCN1C(=O)[[email protected]@H](CCCCN)NC(=O)[[email protected]](CCCCN)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CSSC[[email protected]](NC(=O)[[email protected]](CCCCN)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC2=O)C(=O)N[[email protected]@H](CCCNC(N)=N)C(O)=O)NC(=O)[[email protected]](CC1=CC=C(O)C=C1)NC(=O)[[email protected]](CCCNC(N)=N)NC(=O)[[email protected]@H](N)CCCNC(N)=N

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

Structured Indications
Not Available
Pharmacodynamics

T131, an orally-administered therapy, is expected to lower blood glucose in type II diabetic patients by improving the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia

Mechanism of action

T131 is a selective modulator of PPARg (peroxisome proliferator activated receptor gamma), a receptor involved in regulating the body’s ability to respond to insulin. T131 is not structurally related to the thiazolidinedione class of PPARg agonists, which includes Actos and Avandia

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

In preclinical studies comparing T131 to Avandia, T131 demonstrated superior potency and an improved side effect profile. In these studies, T131 treatment did not result in fluid retention or cardiac hypertrophy. In Phase 1 studies with T131, all doses were well tolerated and no serious adverse events were observed.

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
PubChem Compound
16145453
PubChem Substance
175427019
ChemSpider
17301924

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 Solubility0.09 mg/mLALOGPS
logP-1.8ALOGPS
logP-11ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)3.27ChemAxon
pKa (Strongest Basic)12.66ChemAxon
Physiological Charge8ChemAxon
Hydrogen Acceptor Count37ChemAxon
Hydrogen Donor Count35ChemAxon
Polar Surface Area881.08 Å2ChemAxon
Rotatable Bond Count47ChemAxon
Refractivity565.8 m3·mol-1ChemAxon
Polarizability208.03 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5124
Blood Brain Barrier-0.8222
Caco-2 permeable-0.7653
P-glycoprotein substrateSubstrate0.8349
P-glycoprotein inhibitor INon-inhibitor0.9228
P-glycoprotein inhibitor IINon-inhibitor0.9804
Renal organic cation transporterNon-inhibitor0.6511
CYP450 2C9 substrateNon-substrate0.8205
CYP450 2D6 substrateNon-substrate0.7884
CYP450 3A4 substrateNon-substrate0.5857
CYP450 1A2 substrateNon-inhibitor0.842
CYP450 2C9 inhibitorNon-inhibitor0.8117
CYP450 2D6 inhibitorNon-inhibitor0.8597
CYP450 2C19 inhibitorNon-inhibitor0.7535
CYP450 3A4 inhibitorNon-inhibitor0.8569
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9547
Ames testNon AMES toxic0.6682
CarcinogenicityNon-carcinogens0.8674
BiodegradationNot ready biodegradable0.9136
Rat acute toxicity2.6246 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.875
hERG inhibition (predictor II)Non-inhibitor0.5253
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

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

Drug created on November 18, 2007 11:25 / Updated on December 01, 2017 15:36