aurora A inhibitor / Elara - LARVOL DELTA

Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P1; N=49; Active, not recruiting; Sponsor: University of Colorado, Denver; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Breast Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • HER-2

A selective Aurora-A 5'-UTR siRNA inhibits tumor growth and metastasis. (PubMed, Cancer Lett) - "Mice orthotopically injected with colorectal cancer cells, LNA-siRNA-2 treatment not only inhibited the tumor growth but also blocked liver and lung metastasis. The results of our study suggest that LNA-siRNA-2 has the potential to be a novel therapeutic agent for cancer treatment."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Co-delivery of Aurora-A inhibitor XY-4 and Bcl-xl siRNA enhances antitumor efficacy for melanoma therapy. (PubMed, Int J Nanomedicine) - "Moreover, intratumoral injection of this co-delivery formulation efficiently inhibited the growth of a B16 melanoma xenograft model in vivo. By co-delivering Aurora-A kinase inhibitor XY-4 and Bcl-xl targeting siRNA in a nanoformulation, our study supplied a potential combination strategy for melanoma therapy."

Clinical • Journal • Biosimilar • Melanoma • Oncology • Solid Tumor

MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors. (PubMed) - "Investigational agents MLN8054 (8) and alisertib (MLN8237, 10) have been identified as high affinity, selective, orally bioavailable inhibitors of Aurora A that have advanced into human clinical trials. Alisertib (10) is currently being evaluated in multiple Phase II and III clinical trials in hematological malignancies and solid tumors."

Journal • Biosimilar • Leukemia • Oncology

Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: University of Colorado, Denver; Trial completion date: Nov 2020 ➔ Nov 2021; Trial primary completion date: Feb 2020 ➔ Feb 2021

Clinical • Trial completion date • Trial primary completion date • ER • HER-2

Aurora A inhibition disrupts chromosome condensation and spindle assembly during the first embryonic division in pigs. (PubMed, Reprod Domest Anim) - "Then, the potential role of Aurora A was further evaluated using a highly selective Aurora A inhibitor, MLN8054, during this mitotic progression in pig embryos. Further subcellular structure examination showed that Aurora A inhibition not only led to the failure of spindle microtubule assembly, but also resulted in severe defects in chromosome condensation, accompanied by an obvious decrease in p-TACC3(S558) expression during the prophase of the first mitosis. Together, these results illustrated that Aurora A is crucial for both spindle assembly and chromosome condensation during the first mitotic division in pig embryos, and that the regulation of Aurora A may be associated with its effects on p-TACC3(S558) expression."

Journal • TACC3

Synthesis and identification of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl as potential Aurora A inhibitors. (PubMed, Bioorg Med Chem) - "Herein, we reported a series of 2,4-bisanilinopyrimidines bearing 2,2,6,6-tetramethylpiperidine-N-oxyl with selective inhibition of Aurora A in either enzymatic assays or cellular phenotypic assays, and displaying more potent anti-proliferation compared with that of VX-680. Mechanistic studies revealed that 10a disrupt the spindle formation, block the cell cycle progression in the G2/M phase and induce apoptosis in HeLa cell. These results suggested that the produced series of compounds are potential anticancer agents for further development as selective Aurora A inhibitors."

Journal

Aurora A kinase activity is required to maintain the spindle assembly checkpoint active during pro-metaphase. (PubMed, J Cell Sci) - "We observed that a loss of Aurora A activity directly affects SAC function, that Aurora A is essential for maintaining the checkpoint protein Mad2 on unattached kinetochores, and that inhibition of Aurora A leads to SAC extinction, even in the presence of nocodazole or taxol. This is a new finding that should affect the way Aurora A inhibitors are used in cancer treatments."

Journal

Aurora-A inhibition eliminates myeloid cell-mediated immunosuppression and enhances the efficacy of anti-PD-L1 therapy in breast cancer. (PubMed, Cancer Res) - "The Aurora A inhibitor alisertib shows encouraging activities in clinical trials against advanced breast cancer. Intriguingly, alisertib combined with PD-L1 blockade showed synergistic efficacy in the treatment of mammary tumors. These results detail the effects of Aurora-A inhibition on the immune microenvironment and provide a novel chemo-immunotherapy strategy for advanced breast cancers."

Clinical • Journal

Aurora A regulates the architecture of the Golgi apparatus. (PubMed, Exp Cell Res) - "Golgi dispersal was also induced by a selective Aurora A inhibitor, MLN8237. Knockdown or inhibition of Aurora A also led to aberrant integrity of centrosome and Golgi apparatus during interphase. These results suggest that Aurora A activity is involved in the maintenance of Golgi architecture and the relationship between the Golgi apparatus and centrosome."

Journal

Phase I Study of MLN0128 and MLN8237 in Patients With Advanced Solid Tumors and Metastatic Triple-negative Breast Cancer (clinicaltrials.gov) - P1; N=56; Recruiting; Sponsor: University of Colorado, Denver; Trial completion date: Nov 2018 ➔ Nov 2020; Trial primary completion date: Nov 2018 ➔ Nov 2019

Clinical • Trial completion date • Trial primary completion date