Miransertib (ARQ 092)


Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. 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. Miransertib is currently in a Phase 1/2 company-sponsored study for overgrowth diseases, a Phase 1 study for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH), and a Phase 1b study in combination with the hormonal therapy, anastrozole, in patients with advanced endometrial cancer with AKT and PI3K mutations.

Miransertib has demonstrated inhibition of tumor growth and downstream AKT signaling in vivo in tumors whose growth is driven by these targets. Single agent activity with miransertib was observed in Phase 1a and Phase 1b studies as well as reductions in expression levels of relevant biomarkers. Publications support AKT1 as a viable target in oncology and Proteus syndrome.

Mechanism of Action

Miransertib is a potent small molecule pan-AKT inhibitor that suppresses the AKT pathway via two modes of action. First, miransertib binds inactive AKT, preventing membrane localization and subsequent AKT activation. Second, miransertib binds active AKT, resulting in direct inhibition.

Precision Medicine

The AKT1 mutation is believed to play a role in a number of cancers and overgrowth diseases, such as Proteus syndrome and PROS (PIK3CA-related overgrowth spectrum).

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


Current Clinical Trials

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