ARQ 751 - ArQule

Overview/Mechanism of Action

The AKT pathway is one of the most commonly dysregulated pathways in cancer, making it an attractive target for cancer therapy. ARQ 751 is an orally available, highly selective, next generation pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Additionally, it binds both the active and inactive forms of AKT which directly inhibits and prevents membrane localization, repectively. ARQ751 was designed to be more potent and selective than miransertib, with a wider therapeutic index and predictable PK. A phase 1 biomarker driven trial in advanced solid tumors with AKT, PI3K and PTEN mutations commenced in mid-2016. ARQ 751 has demonstrated inhibition of tumor growth and downstream AKT signaling in vivo in tumors whose growth is driven by these targets. ARQ 751 publications support AKT1 as a viable target in oncology and rare diseases. We are currently conducting a phase 1b trial in patients with solid tumors harboring AKT, PIK3CA or PTEN mutations.

Precision Medicine

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 as well as to select non-oncology indications. Preclinical research has demonstrated that ARQ 751 potently and selectively inhibits both the active and inactive forms of AKT, with potent anti-tumor activity demonstrated in PI3K/AKT driven tumor models.

Planned/Ongoing Clinical Trials


The prevalence of AKT1 mutations in cancer varies from 3-5% depending on tumors. The tumor types with the highest prevalence of AKT1 mutations are breast, bladder, endometrial, ovarian and cervical cancers. PIK3CA (the gene that codes for an important subunit of P13K) mutations are even more prevalent in multiple solid tumors, such as colon (32%) and brain (27%), etc.

Current Clinical Trials

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