Delving into the Latest Updates on PPA24 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

PP2A

Mechanism

PP2A stimulants(Protein phosphatase 2A stimulants)

Therapeutic Areas

NeoplasmsDigestive System DisordersSkin and Musculoskeletal Diseases

Active Indication

MelanomaColonic Cancer

Inactive Indication-

Originator Organization

Penn State Hershey College of Medicine

Active Organization

Penn State Hershey College of Medicine

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC22H27BrClN5S

InChIKeyUXJLBJDEPANSAH-UHFFFAOYSA-M

CAS Registry3035032-77-7

A series of compounds were designed utilizing molecular modeling and fragment-based design based upon the known protein phosphatase 2A (PP2A) activators, NSC49L and iHAP1, and evaluated for their ability to inhibit the viability of colorectal cancer (CRC) and folinic acid, 5-fluorouracil, and oxaliplatin (FOLFOX)-resistant CRC cells. PPA24 (19a) was identified as the most cytotoxic compound with IC₅₀ values in the range of 2.36-6.75 μM in CRC and FOLFOX-resistant CRC cell lines. It stimulated PP2A activity to a greater extent, displayed lower binding energies through molecular docking, and showed higher binding affinity through surface plasmon resonance for PP2A catalytic subunit α than the known PP2A activators. PPA24 dose-dependently induced apoptosis and oxidative stress, decreased the level of c-Myc expression, and synergistically potentiated cytotoxicity when combined with gemcitabine and cisplatin. Furthermore, a PPA24-encapsulated nanoformulation significantly inhibited the growth of CRC xenografts without systemic toxicities. Together, these results signify the potential of PPA24 as a novel PP2A activator and a prospective therapeutic for CRC and FOLFOX-resistant CRC.

100 Deals associated with PPA24

Login to view more data