Delving into the Latest Updates on OBX1-012 with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

EGFR T790M

Mechanism

EGFR T790M inhibitors(EGFR T790M inhibitors)

Therapeutic Areas

NeoplasmsRespiratory Diseases

Active Indication

Non-Small Cell Lung Cancer

Inactive Indication-

Originator Organization

University of Ulsan

Active Organization

University of Ulsan

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

BACKGROUNDDespite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now.OBJECTIVETo determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR.METHODSEffects of OBX1-012 on cellular viability and EGFR-related signaling were determined in EGFR-mutant non-small cell lung cancer (NSCLC) cells, including cells harboring T790M mutations. In addition, in vivo efficacy of OBX1-012 was evaluated in xenograft models.RESULTSWe report the discovery and preclinical assessment of another novel, mutant-selective EGFR-TKI, OBX1-012. Compared with other mutant-selective EGFR-TKIs such as olumitinib and osimertinib, it showed similar potency and selectivity for mutant EGFR. OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells.CONCLUSIONSThese results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC.

100 Deals associated with OBX1-012

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