HomeAt AACR meeting Nerviano Medical Sciences presents new evidences on its own FLT3/KIT/CSF1R inhibitor and its activities on the identification and characterization of ATP-mimetic choline kinase inhibitors.

At AACR meeting Nerviano Medical Sciences presents new evidences on its own FLT3/KIT/CSF1R inhibitor and its activities on the identification and characterization of ATP-mimetic choline kinase inhibitors.

Nerviano, 03.04.2019

Nerviano Medical Sciences presents two posters at the American Association for Cancer Research (AACR) Annual Meeting in, Atlanta, Georgia, USA regarding preclinical efficacy and safety of NMS-P088, a potent FLT3, KIT and CSF-1R inhibitor with in vitro and in vivo activity also in presence of the gatekeeper mutation, and about the Identification and characterization of ATP-mimetic choline kinase inhibitors.

During the event  researchers describe new in vitro and in vivo data regarding the activity of NMS-P088 against CSF-1R. The inhibitory effect of NMS-P088 on blast samples of CMML patients, that show high expression of CSF-1R, is also presented. Based on NMS-P088 original kinase targets profile, including FLT3 and KIT gatekeeper resistance mutations as well as CSF1R, preclinical efficacy and safety, a Phase I/II clinical trial was started to potentially address unmet medical needs in AML and CMML.

The second presentation regards identification and characterization of ATP-mimetic choline kinase inhibitors. The chemical expansion of ATP-mimetic quinazoline class allowed identification of potent compounds, both in biochemical and in cellular assay, with selectivity against ChoKß and a panel of 60 tyrosine and serine/threonine kinases. Preliminary genomic analysis identified genes differentially expressed in sensitive versus resistant cell lines. Further studies are ongoing to confirm these genes as predictive biomarkers of sensitivity to compounds and to identify other sensitive cancer cell lines. A structure-based drug design optimization program is ongoing with the aim of further improving biological and ADME properties.

Both NMS-P088 and the new choline kinase inhibitors are the results of the Kinase platform in Nerviano Medical Sciences. It represents an integrated system of know-how, technologies and intellectual property developed over the years by the Campus and based on protein kinases as molecular targets. The use of this platform allows the Nerviano research Campus a conspicuous synergy in the efficient development of innovative anticancer drugs.

 

Presentation title: NMS-P088, a novel FLT3, KIT and CSF1R inhibitor, is a promising clinical candidate for AML and CMML treatment. Marina Ciomei et Al.
Meeting: American Association for Cancer Research (AACR) Annual Meeting March 29 - Apr 3, 2019, Atlanta, Georgia, USA (Abs. 1324)

Presentation title: Identification and characterization of ATP-mimetic choline kinase inhibitors. Paola Gnocchi et al
Meeting: American Association for Cancer Research (AACR) Annual Meeting March 29 - Apr 3, 2019, Atlanta, Georgia, USA (Abs. 4790)

The full posters can be found on the conference website.