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
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
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.
CNS Activity
Originator
Approval Year
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT00806338
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
Edited
Fri Dec 15 16:32:03 GMT 2023
by
admin
on
Fri Dec 15 16:32:03 GMT 2023
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Record UNII |
KKC12PIF16
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Record Status |
Validated (UNII)
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Record Version |
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NCI_THESAURUS |
C29728
Created by
admin on Fri Dec 15 16:32:03 GMT 2023 , Edited by admin on Fri Dec 15 16:32:03 GMT 2023
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Code System | Code | Type | Description | ||
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Trodusquemine
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186139-09-3
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C123882
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300000034424
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NN-45
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8284
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DB06333
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KKC12PIF16
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DTXSID701317590
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CHEMBL508583
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9917968
Created by
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Related Record | Type | Details | ||
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TARGET -> INHIBITOR |
IC50
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SALT/SOLVATE -> PARENT |
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PARENT -> ACTIVE CONSTITUENT ALWAYS PRESENT |
Isolated from liver.
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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