# Development of VNLG-152R as novel therapeutic for triple negative breast cancer

> **NIH NIH R44** · ISOPRENE PHARMACEUTICALS, INC. · 2022 · $995,100

## Abstract

Project Title: Development of Mnk1/2 Degrader, VNLG-152 as Novel Therapeutic for Triple Negative Breast
Cancer
PROJECT SUMMARY/ABSTRACT
 Currently, there are no effective therapies for patients with triple negative (ERα, PR, and Her2 negative) breast
cancer (TNBC), an aggressive and highly metastatic disease. Activation of eukaryotic initiation factor 4E (eIF4E) by
mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (Mnk1/2) play a critical role in the development,
progression and metastasis of TNBC. It is important to note that Mnk1/2 activity and the phosphorylation of
eIF4E are dispensable for normal development, thus making Mnk1/2 attractive therapeutic targets. We have
recently shown that proprietary Isoprene Pharmaceuticals Inc. (IPI) novel retinamides (NRs) exhibit exquisite anti-
TNBC activities in vitro and in vivo against MDA-MB-231 tumor xenografts, metastasis and TNBC patient-derived
xenografts (PDX) in mice. To translate these findings towards human clinical trials, we have identified novel
compounds, racemic VNLG-152 (VNLG-152R), with three back-up compounds (VNLG-153, VNHM-1-73 and VNHM-
1-81) that induce Mnk1/2 degradation (with consequent depletion of oncogenic peIF4E). By targeting Mnk1/2 protein
degradation, VNLG-152R potently inhibited both Mnk-eIF4E and mTORC1 signaling pathways and strongly regulates
downstream factors involved in cell cycle regulation, apoptosis, pro-inflammatory cytokines/chemokines secretion,
epithelial-mesenchymal transition (EMT) and metastasis. Most importantly, orally bioavailable VNLG-152R exhibited
remarkable dose-dependent antitumor (91 to 100% growth inhibition) and antimetastatic (~80% inhibition) activities
against cell line and patient-derived TNBC xenograft models, with no apparent host toxicity. Collectively, these studies
demonstrate that targeting Mnk-eIF4E/mTORC1 signaling with a potent Mnk1/2 degrader, VNLG-152R, is a novel
therapeutic strategy that can be developed as monotherapy for the effective treatment of patients with both primary
and metastatic TNBC. With support from Maryland Innovative Initiation (MII) award we have successfully completed
all the aims of our SBIR Phase-1-type R&D study as well as conducted many additional studies that were not
originally anticipated. We now seek Direct-to-Phase II SBIR support to advance VNLG-152R through various IND-
enabling pre-clinical development activities. Our goal is to develop VNLG-152R as an oral targeted anticancer agent
for effective treatment of the difficult-to-treat primary and metastatic TNBC.
 The specific aims for this Direct-to-Phase II SBIR proposal are:
 1. Synthesize 300 g of non-GMP VNLG-152R for preclinical studies, including analytical characterization,
 formulation and use this agent to support GLP preclinical studies.
 2. Conduct ancillary pharmacology with VNLG-152R using in vitro and in vivo models of TNBC.
 3. Conduct IND-enabling studies, including GLP toxicity and toxicokinetics studies in two rele...

## Key facts

- **NIH application ID:** 10474986
- **Project number:** 5R44CA257495-02
- **Recipient organization:** ISOPRENE PHARMACEUTICALS, INC.
- **Principal Investigator:** VINCENT Collins Ofuka NJAR
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $995,100
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10474986

## Citation

> US National Institutes of Health, RePORTER application 10474986, Development of VNLG-152R as novel therapeutic for triple negative breast cancer (5R44CA257495-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10474986. Licensed CC0.

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