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Details

Stereochemistry ABSOLUTE
Molecular Formula C37H72N4O5S
Molecular Weight 685.056
Optical Activity UNSPECIFIED
Defined Stereocenters 11 / 11
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TRODUSQUEMINE

SMILES

[H][C@@]1(CC[C@@]2([H])[C@]3([H])[C@H](O)C[C@@]4([H])C[C@H](CC[C@]4(C)[C@@]3([H])CC[C@]12C)NCCCNCCCCNCCCN)[C@H](C)CC[C@@H](OS(O)(=O)=O)C(C)C

InChI

InChIKey=WUJVPODXELZABP-FWJXURDUSA-N
InChI=1S/C37H72N4O5S/c1-26(2)34(46-47(43,44)45)13-10-27(3)30-11-12-31-35-32(15-17-37(30,31)5)36(4)16-14-29(24-28(36)25-33(35)42)41-23-9-22-40-20-7-6-19-39-21-8-18-38/h26-35,39-42H,6-25,38H2,1-5H3,(H,43,44,45)/t27-,28-,29+,30-,31+,32+,33-,34-,35+,36+,37-/m1/s1

HIDE SMILES / InChI

Molecular Formula C37H72N4O5S
Molecular Weight 685.056
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 10 / 11
E/Z Centers 0
Optical Activity UNSPECIFIED

Trodusquemine (MSI-1436) is a "first-in-class" highly selective non-competitive, allosteric inhibitor of PTP1B that can cross the blood-brain barrier to suppress feeding and promote insulin sensitivity and glycemic control. Trodusquemine is a naturally occurring cholestane that can be purified from the liver of the dogfish shark, Squalus acanthias, but it can also be manufactured synthetically by a fairly laborious process that requires several weeks. Trodusquemine has potential hypoglycemic, anti-diabetic, anti-obesity, and antineoplastic activities. Upon administration, trodusquemine selectively targets and inhibits PTP1B, thereby preventing PTP1B-mediated signaling. This prevents the dephosphorylation of the insulin receptor, which improves insulin signaling and insulin sensitivity, and decreases blood glucose levels. In susceptible cancer cells, inhibition of PTP1B causes a reduction of tumor cell proliferation.

Approval Year

PubMed

PubMed

TitleDatePubMed
Discovery of a novel series of inhibitors of lymphoid tyrosine phosphatase with activity in human T cells.
2011 Mar 24
Multistep Inhibition of α-Synuclein Aggregation and Toxicity in Vitro and in Vivo by Trodusquemine.
2018 Aug 17
Patents

Sample Use Guides

Diabetes Mellitus; Obesity: Trodusquemine 3 - 10 mg/m2. A single dose of Trodusquemine will be administered every 72 hours on Days 0, 3, 6, 9, 12, 15, 18 and 21. Doses are 3mg/m2 in cohort 1, 6mg/m2 in cohort 2 and 10mg/m2 in cohort 3.
Route of Administration: Intravenous
Trodusquemine (MSI-1436) inhibits protein-tyrosine phosphatase 1B (PTB1B) with an IC50 of appr 1 uM, 200-fold preference over TCPTP (IC50, 224 uM). MSI-1436 (10 uM) restores ERK phosphorylation in response to mGluR1/5 agonist DHPG in F11 neuronal cells. MSI-1436 (10 uM) rescues DHPG-induced holding currents and restores DSI in LMO4KO BLA neurons.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:32:03 UTC 2023
Edited
by admin
on Fri Dec 15 16:32:03 UTC 2023
Record UNII
KKC12PIF16
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TRODUSQUEMINE
INN   USAN  
USAN   INN  
Official Name English
MSI-1436
Code English
trodusquemine [INN]
Common Name English
(24R)-3β-[[3-[[4-[(3-aminopropyl)amino]butyl]amino]propyl]amino]-7α-hydroxy-5α-cholestan-24-yl hydrogen sulfate
Systematic Name English
TRODUSQUEMINE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29728
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
Code System Code Type Description
WIKIPEDIA
Trodusquemine
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
CAS
186139-09-3
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
NCI_THESAURUS
C123882
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
SMS_ID
300000034424
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
USAN
NN-45
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
INN
8284
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
DRUG BANK
DB06333
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
FDA UNII
KKC12PIF16
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
EPA CompTox
DTXSID701317590
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
ChEMBL
CHEMBL508583
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
PUBCHEM
9917968
Created by admin on Fri Dec 15 16:32:03 UTC 2023 , Edited by admin on Fri Dec 15 16:32:03 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
IC50
SALT/SOLVATE -> PARENT
PARENT -> ACTIVE CONSTITUENT ALWAYS PRESENT
Isolated from liver.
Related Record Type Details
ACTIVE MOIETY