Glioblastoma multiforme (GBM) is the most malignant primary brain cancer. Despite aggressive treatments currently there is no cure for GBM. Many challenges should be considered for the development of new therapeutical agents for glioblastoma, including appropriate target selectivity and pharmacokinetics. Several mutations and alterations of key cellular pathways including tyrosine kinases (TKs) are involved in malignant transformation and tumor progression. Thus, the targeting of multiple pathways and the development of innovative combination drug regimens is expected to yield improved therapies. Moreover, the abilities to cross the blood-brain barrier (BBB) reaching effective concentrations in brain and to remain into this tissue avoiding the effects of efflux transporters are also critical issues in the development of new therapeutics for GBM. CR13626 is a novel brain penetrant small molecule able to potently inhibit in vitro the activity of EGFR, VEGFR2 (aka KDR), Fyn, Yes, Lck, HGK (aka MAP4K4) and RET kinases relevant for GBM development. CR13626 shows good oral bioavailability (72%) and relevant brain penetration (brain/plasma ratio of 1.4). In an orthotopic xenograft glioblastoma mouse model, oral treatment with CR13626 results in a time-dependent reduction of tumor growth, leading to a significant increase of animal survival. The unique properties of CR13626 warrant its further investigation as a potential new drug candidate in glioblastoma.

项与 CR-13626 相关的新闻（医药）

2019-09-18

·rottapharmbiotech

Rottapharm Biotech to present at EANO 2019 the key preclinical results of its selective multikinase inhibitor for glioblastoma

Highlights include the unique ability of CR13626 to enter (and remain in) the brain, to selectively inhibit multiple tyrosine kinases (EGFR, VEGFR2, FYN and YES) that specifically fuel tumour growth, and to increase survival in a mouse model of glioblastoma Monza (Italy), 18 September 2019 Rottapharm Biotech, an R&D company dedicated to innovative drug discovery and development, today announced that the key preclinical data of CR13626, its novel small molecule candidate for the treatment of glioblastoma, will be released at the 14th Meeting of the European Association of Neuro-Oncology (EANO) in Lyon, France, September 19-22, 2019. The presentation “CR13626, an oral tyrosine kinase inhibitor crossing the blood brain barrier, reduces tumour growth and prolongs survival in a mouse model of glioblastoma”, will take place on 20 September. “Glioblastoma is the most malignant form of primary brain cancer, and treatment options are still far from being optimal. Tumour heterogeneity and the inability of molecules to reach and stay in the brain, are among the main causes of therapeutic failure” said Dr. Lucio Rovati, CEO and CSO of Rottapharm Biotech. “CR13626 emerged from our large research program on kinase inhibitors as a product with the right characteristics for targeting glioblastoma”. Dr. Gianfranco Caselli, director of Pharmacology and Toxicology at Rottapharm Biotech added “CR13626 selectively blocks multiple kinases relevant to glioblastoma and crosses the blood-brain barrier without being a substrate of the efflux transporters that push drugs out of the brain, thus contributing to tumour resistance. The present findings prove our original hypothesis: the unique ability of CR13626 to work efficiently in the brain tumour and surrounding microenvironment translates into a marked inhibition of cancer growth and a significantly increased survival of mice orthotopically implanted with human glioblastoma cells”. The abstract is published in the Journal Neuro-Oncology and available online at http://academic.oup.com.libproxy1.nus.edu.sg/neuro-oncology. About glioblastoma Glioblastoma is a tumour characterized by high grade of cellular proliferation, invasiveness, cellular atypia and angiogenesis, all of which contribute to its poor prognosis (with a patient median survival of approximately 15 months from diagnosis, and only 5% of patients with a five-year survival). About Rottapharm Biotech Rottapharm Biotech is an R&D company dedicated to innovative drug discovery and development. Rottapharm Biotech operates with a mixed discovery model that includes new chemical entities (small molecules) and a proprietary technology platform for the generation and selection of monoclonal antibodies. The R&D expertise embraces medicinal/computational chemistry, new target validation, pharmacological and pharmacokinetic characterization of new drug candidates, and design and conduct of innovative clinical trials. The company pipeline covers different therapeutic areas with focus on rheumatology (rheumatoid arthritis and osteoarthritis), pain and inflammation, immunomodulation and immuno-oncology, and selected oncology areas. The company strategy is to look for partnership at an early stage of development, ranging from preclinical significant stages to phase II proof-of-concept trials. For additional information about the company, please visit www.rottapharmbiotech.com. Rottapharm Biotech contacts Federica Girolami (Scientific Liaisons and Business Development Director) federica.girolami@rottapharmbiotech.com

100 项与 CR-13626 相关的药物交易

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