Miransertib (ARQ 092) - ArQule

Overview/Mechanism of Action

Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT 1, 2 and 3 isoforms. Additionally, it binds both the active and inactive forms of AKT which directly inhibits and prevents membrane localization, respectively.  Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers; however, there are currently no approved inhibitors of AKT. AKT inhibitors, either as single agent or combination therapy, show significant promise in molecularly defined patient populations. We are currently initiating a registrational trial in both Proteus syndrome and PIK3CA-Related Overgrowth Spectrum (PROS) and further information related to these diseases and trials can be found in our orphan disease-focused presentation, PROS and PS Primer 2019.

Precision Medicine

The AKT1 mutation is believed to play a role in multiple cancers and overgrowth diseases, such as Proteus syndrome and PROS. The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis. This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers and non-oncology indications. Preclinical research has demonstrated that miransertib suppresses PIK3CA/AKT1 mutant dependent kinase signaling and demonstrates anti-tumor activity in molecularly defined tumor models.

A landmark discovery by researchers from the National Human Genome Research Institute at the NIH demonstrated that a somatic mosaic mutation in the AKT1 oncogene is the underlying genetic alteration that causes Proteus syndrome. A spontaneous point mutation – a single-letter “misspelling” in the DNA of the genetic code — in the AKT1 gene during embryological development is responsible for activating the tissue growth characteristic of Proteus syndrome. The identification of the causal mutation of Proteus syndrome allows for the development of molecularly targeted treatments.

Planned/Ongoing Clinical Trials

Rare Diseases

Oncology

Current Clinical Trials

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