The purpose of repurposing

Barrett, James E.; Kim, Felix J.

doi:10.18632/oncotarget.14806

Cited by 1 publication

(1 citation statement)

References 8 publications

(13 reference statements)

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“…To overcome these challenges, drug repurposing, also broadly referred to as drug repositioning, reprofiling or rescue, which investigates existing and investigational drugs for their potential application for other diseases has gained traction. This approach has the potential to significantly shorten the drug development process as, in most cases, the drugs will have been through several stages of clinical development and will therefore have well-known pharmacokinetic and safety profiles (Ashburn and Thor, 2004[ 3 ]; Oprea and Mestres, 2012[ 60 ]; Njoroge et al, 2014[ 59 ]; Barrett and Kim, 2017[ 6 ]). To date there are a wide range of drugs that show promise for being repurposed as anti-cancer agents, with approximately 190 of them currently in late-stage clinical trials.…”

Section: Introductionmentioning

confidence: 99%

The diaryl-imidazopyridazine anti-plasmodial compound, MMV652103, exhibits anti-breast cancer activity

Neumann-Mufweba,

Kimani,

Khan

et al. 2022

EXCLI Journal; 21:Doc656; ISSN 1611-2156

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Breast cancer is the most common malignancy in women worldwide and it remains a global health burden, in part, due to poor response and tolerance to current therapeutics. Drug repurposing, which seeks to identify new indications for existing and investigational drugs, has become an exciting strategy to address these challenges. Here we describe the anti-breast cancer activity of a diaryl-imidazopyridazine compound, MMV652103, which was previously identified for its anti-plasmodial activity. We demonstrate that MMV652103 potently inhibits the oncogenic PI4KB and PIK3C2G lipid kinases, is selectively cytotoxic to MCF7 and T47D estrogen receptor positive breast cancer cells and inhibits their ability to survive and migrate. The underlying mechanisms involved included the induction of reactive oxygen species and activation of the DNA damage and p38 MAPK stress signaling pathways. This was associated with a G1 cell cycle arrest and an increase in levels of the cyclin-dependent kinase inhibitor p21 and activation of apoptotic and autophagic cell death pathways. Lastly, MMV652103 significantly reduced the weight and metastases of MCF7 induced tumors in an in vivo chick embryo model and displayed a favorable safety profile. These findings position MMV652103 as a promising chemotherapeutic in the treatment of oestrogen receptor positive breast cancers.

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