TP508   Click here for help

GtoPdb Ligand ID: 9284

Synonyms: Chrysalin
Compound class: Peptide or derivative
Comment: TP508 is a synthetic 23 amino acid peptide corresponding to amino acids 183 to 205 of the endogenous wound healing molecule human thrombin [8]. TP508 has been investigated as an activator of soft and hard tissue repair [1,4-5,7,9], and for its potential to mitigate tissue damage caused by radiation exposure [3,6]. TP508 may also provide an alternative to stem cell therapy in regenerative medicine.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES NCCCCC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NC(C(=O)NC(C(=O)NCC(=O)NC(C(=O)NC(C(=O)NCC(=O)NCC(=O)N1CCCC1C(=O)NC(C(=O)NC(C(=O)O)C(C)C)Cc1ccccc1)CO)CC(=O)O)CCC(=O)O)CS)C)CC(=O)O)CCCN=C(N)N)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C1CCCN1C(=O)C(NC(=O)C(Cc1ccc(cc1)O)NC(=O)CNC(=O)C(N)C)CCCCN)CC(=O)O)CCC(=O)O
Isomeric SMILES CC(C)[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)CNC(=O)[C@H](C)N)C(=O)O
InChI InChI=1S/C97H146N28O36S/c1-48(2)79(96(160)161)123-91(155)60(35-51-15-6-5-7-16-51)119-93(157)66-20-13-33-124(66)73(133)45-104-68(128)40-106-85(149)64(46-126)121-89(153)62(38-77(140)141)114-72(132)44-109-84(148)57(27-29-75(136)137)117-92(156)65(47-162)122-81(145)50(4)110-87(151)61(37-76(138)139)113-71(131)43-107-82(146)54(19-12-32-103-97(101)102)115-86(150)55(17-8-10-30-98)111-69(129)42-108-83(147)56(26-28-74(134)135)116-90(154)63(39-78(142)143)120-94(158)67-21-14-34-125(67)95(159)58(18-9-11-31-99)118-88(152)59(36-52-22-24-53(127)25-23-52)112-70(130)41-105-80(144)49(3)100/h5-7,15-16,22-25,48-50,54-67,79,126-127,162H,8-14,17-21,26-47,98-100H2,1-4H3,(H,104,128)(H,105,144)(H,106,149)(H,107,146)(H,108,147)(H,109,148)(H,110,151)(H,111,129)(H,112,130)(H,113,131)(H,114,132)(H,115,150)(H,116,154)(H,117,156)(H,118,152)(H,119,157)(H,120,158)(H,121,153)(H,122,145)(H,123,155)(H,134,135)(H,136,137)(H,138,139)(H,140,141)(H,142,143)(H,160,161)(H4,101,102,103)/t49-,50-,54-,55-,56-,57-,58-,59-,60-,61-,62-,63-,64-,65-,66-,67-,79-/m0/s1
InChI Key MOZAQZCGIKWACU-VKDININFSA-N
No information available.
Summary of Clinical Use Click here for help
Results from a placebo-controlled Phase 1/2 clinical trial showed that TP508 stimulated healing of diabetic foot ulcers [2]. A Phase 2 (NCT00131482) study to evaluate TP508's ability to promote bone healing was terminated as the agent did not demonstrate benefit compared to placebo.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Thrombin and thrombin peptides play a role in initiating tissue repair. Mechanistically, TP508 appears to act on a non-proteolytically active receptor (non-PAR) pathway of tissue repair, which involves increased growth factor production and promotion of angiogenesis [9-10]. TP508 is also reported to induce NO via integrin αvβ3 binding in endothelial cells. This effect is dependent on the RGD motif (Arg-Gly-Asp) contained within the peptide sequence [1]. The RGD motif is buried within the structure of intact thrombin and is only exposed following proteolytic cleavage or protein unfolding. The RGD motif is required for thrombin binding to αvβ3 and α5β1 integrins.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT00131482 A Study to Evaluate the Safety and Effectiveness of Different Doses of Chrysalin in Adults Who Have a Broken Wrist Phase 2 Interventional Capstone Therapeutics