Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Sapanisertib is an oral dual inhibitor of mTORC1/mTORC2, discovered by Intellikine for the treatment of cancer. The drug is being tested in phase II of clinical trials for different cancers among which are sarcoma, hepatocellular carcinoma, etc. The drug is currently developed by Takeda with breast cancer, renal cancer and endometrial cancer being the main target indications.

Cevipabulin is a synthetic, water-soluble tubulin-binding agent with potential antineoplastic activity. Cevipabulin appears to bind at the vinca-binding site on tubulin but seems to act more similar to taxane-site binding agents in that it enhances tubulin polymerization and does not induce tubulin depolymerization. The disruption in microtubule dynamics may eventually inhibit cell division and reduce cellular growth.

Atopaxar, also known as E 5555 is a novel reversible protease-activated receptor-1 (PAR-1) thrombin receptor antagonist. The inhibition of thrombin-mediated platelet activation by means of protease-activated receptor-1 inhibitors represents an attractive therapeutic option for patients with atherothrombotic disease processes. In preclinical studies, atopaxar demonstrated inhibition of thrombin receptor-activating peptides (TRAP)- and thrombin-induced platelet aggregation. Atopaxar was being developed by Eisai for acute coronary syndromes (ACS) and coronary disorders, including atherothrombosis, unstable angina pectoris and myocardial infarction. Atopaxar was in phase II clinical development in the US, EU and Japan. However, development was discontinued in May 2012.

BGT 226 is an orally available, small molecule, the dual inhibitor of mammalian target of rapamycin (mTOR) and phosphatidylinositol 3'kinase (PI3K), developed by Novartis for the treatment of solid tumors, including advanced breast cancer. A phase I/II trial was completed in the US, Canada, and Spain, and a phase I trial was completed in Japan. However, development appears to have been discontinued.

Voxtalisib (SAR245409, XL765) is an orally available inhibitor of PI3K and the mammalian target of rapamycin (mTOR), which are frequently activated in human tumors and play central roles in tumor cell proliferation. Exelixis discovered Voxtalisib internally and out-licensed the compound to Sanofi. Voxtalisib is being evaluated by Sanofi as a single agent and in multiple combination regimens in a variety of cancer indications. Clinical trials have included a single agent phase 2 trial in Non-Hodgkin’s lymphoma, combination phase 1b/2 trials with temozolomide in patients with glioblastoma, with letrozole in hormone receptor positive breast cancer, with bendamustine and/or rituximab in lymphoma or leukemia, and a phase 1 trial in combination with a MEK inhibitor. Voxtalisib is a highly selective, potent and reversible ATP-competitive inhibitor of pan-Class I PI3K (α, β, γ, and δ) and mTORC1/mTORC2. It is orally active, highly selective over 130 other protein kinases. In cellular assays, XL765 inhibits the formation of PIP3 in the membrane, and inhibits phosphorylation of AKT, p70S6K, and S6 phosphorylation in multiple tumor cell lines with different genetic alterations affecting the PI3K pathway.

Quisinostat is an orally bioavailable potent histone deacetylase inhibitor, specifically selected due to its sustained inhibition of HDAC1 in solid tumor tissues and prolonged period of half-elimination from tissues. Phase 2 clinical trials are ongoing in patients with platinum-resistant ovarian cancer and non-small cell lung cancer (NSCLC). Quisinostat is active in the treatment of patients with relapsed or refractory Sézary syndrome. The most common drug-related adverse events reported in this trial were: nausea, diarrhea, asthenia. Grade 3 adverse events were also reported: hypertension, lethargy and pruritus.