Drug intelligence / Profile preview

NV-128

Development stage
Preclinical
Lead developer
Kazia Therapeutics
Modality
Small Molecules
01

Overview

**NV-128** is a novel synthetic isoflavone derivative and small molecule developed as an antineoplastic agent, primarily targeting chemoresistant ovarian cancer and ovarian cancer stem cells. Its mechanism of action involves dual inhibition of **mTOR complexes (mTORC1 and mTORC2)**, leading to cell death through caspase-independent pathways. It induces dephosphorylation of mTOR, disrupts mitochondrial function (leading to mitochondrial membrane depolarization, ATP depletion, and increased ROS generation), and activates two independent non-canonical cell death pathways: inhibition of mTOR via AMPKα1 (resulting in cellular energy starvation/autophagy) and activation of the MEK/ERK/Bax pathway (resulting in endonuclease G-mediated DNA fragmentation). NV-128 inhibits tumor growth in preclinical models of chemoresistant ovarian cancer without showing apparent toxicity and is distinct from rapalogs by also targeting mTORC2 and inhibiting AKT activation[1][2][3][4][5].

Brand names
NV-128NV128NV 128
Other names
NV-128 isoflavoneNV128 isoflavoneNV 128 isoflavone
02

Targets

ND1 (Mitochondrial electron transport chain complex I)PRKAA1 (AMP-activated protein kinase alpha catalytic subunit isoform alpha-1)BAX (Apoptosis regulator BAX)Mechanistic target of rapamycin complex 1Mechanistic target of rapamycin kinase complex 2MAPK12 (Mitogen-activated protein kinase 12)MEK1 (Dual specificity mitogen-activated protein kinase kinase 1)

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