Delving into the Latest Updates on IIIC3 (Enzo Biochem, Inc.) with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

IIIC3

Target

DKK1

Mechanism

DKK1 inhibitors(Dickkopf-related protein 1 inhibitors)

Therapeutic Areas

Skin and Musculoskeletal Diseases

Active Indication-

Inactive Indication

Bone Diseases

Originator Organization

Enzo Biochem, Inc.

Active Organization-

Inactive Organization

St. Jude Children's Research Hospital, Inc.

University of Connecticut Health Center

Enzo Biochem, Inc.

Drug Highest PhasePendingDiscovery

First Approval Date-

Regulation-

PurposeA chemical approach to examine the role of Wnt signaling in maintaining the stemness and/or proliferation of limbal stem/progenitor cells (LSCs).MethodsLSCs were isolated from human donor eyes and cultured as single cells for 12 to 14 days with the following small molecules: IIIC3, an antagonist of the Wnt signaling inhibitor Dickkopf (DKK), and IC15, a Wnt signaling inhibitor. Proliferation of LSCs in the presence of IIIC3 and IC15 was determined by the number of cells and colonies established. Maintenance of stemness was determined by p63α, cytokeratin (K)12, and K14 expression.ResultsActivation of Wnt, through IIIC3-mediated DKK inhibition, resulted in similar colony forming efficiency (CFE) as in the untreated LSCs, but significantly increased the number of cultivated cells 7.21% with 5 μM. Inhibition of Wnt with IC15 significantly reduced the CFE (P ≤ 0.01) and the number of cultivated cells by 16% to 29%. Percentage of cells expressing high levels of p63α (p63αbright) and quantity of small cells (≤12 μm), which contain the LSCs, increased 4.71% and 11.26% (both P < 0.05), respectively, with 5 μM IIIC3. All concentrations of IIIC3 and IC15 retained the K14 undifferentiated marker (97%), while differentiation, as detected by expression of K12, was found in up to 2% of cells in 1 μM IIIC3, 1 μM IC15, or 5 μM IIIC3.ConclusionsWnt signaling is required in LSC proliferation and maintenance of an undifferentiated state. The current study is a proof of concept that the Wnt pathway could be modulated in LSCs to enhance or decrease the efficiency of human LSC expansion.

100 Deals associated with IIIC3 (Enzo Biochem, Inc.)

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Bone Diseases	Discovery	US	St. Jude Children's Research Hospital, Inc.	-
Bone Diseases	Discovery	US	University of Connecticut Health Center	-
Bone Diseases	Discovery	US	Enzo Biochem, Inc.	-