delcasertib

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Ligands
delcasertib

GtoPdb Ligand ID: 7840

Synonyms: BMS-875944 | CS-9803 | KAI-9803

Compound class: Peptide or derivative

Comment: The synthesis of delcasertib is described in [1]. Delcasertib is a peptidic agent which is an isozyme-selective delta protein kinase C (PKCδ) inhibitor. It consists of a cargo peptide (CSFNSYELGSL) derived from the δV1-1 portion of PKCδ which acts to inhibit PKCδ translocation, conjugated to the cell-penetrating, arginine-rich peptide sequence of the HIV type 1 transactivator protein (TAT_45-57 CYGRKKRRQRRR) which acts as a cellular delivery system.

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Summary of Clinical Use
Delcasertib was developed as a therapy for the prevention of myocardial tissue death and associated congestive heart failure in acute myocardial infarction patients undergoing revascularization procedures. A Phase 1/II clinical trial (NCT00093197) and Phase 2b trial (NCT00785954) have been completed, but delcasertib failed to significantly reduce cardiac tissue damage. There appears to have been no further development of this compound.

Summary of Clinical Use

Delcasertib was developed as a therapy for the prevention of myocardial tissue death and associated congestive heart failure in acute myocardial infarction patients undergoing revascularization procedures. A Phase 1/II clinical trial (NCT00093197) and Phase 2b trial (NCT00785954) have been completed, but delcasertib failed to significantly reduce cardiac tissue damage. There appears to have been no further development of this compound.

Mechanism Of Action and Pharmacodynamic Effects
Reperfusion injury occurs when myocardial and endothelial cells undergo necrosis and apoptosis after the reintroduction of blood flow to the ischemic areas following heart attack. In preclinical studies selective inhibition of the PKCδ isozyme by delcasertib (previously known as KAI-9803) prevented damage to the mitochondria and inhibited both necrosis and apoptosis during reperfusion injury and caused a significant reduction in infarct size and improved heart function [2-3].

Mechanism Of Action and Pharmacodynamic Effects

Reperfusion injury occurs when myocardial and endothelial cells undergo necrosis and apoptosis after the reintroduction of blood flow to the ischemic areas following heart attack. In preclinical studies selective inhibition of the PKCδ isozyme by delcasertib (previously known as KAI-9803) prevented damage to the mitochondria and inhibited both necrosis and apoptosis during reperfusion injury and caused a significant reduction in infarct size and improved heart function [2-3].