Published a study about Activation-Free Sulfonyl Fluoride Probes for Fragment Screening

30/03/2023 Publications Published a study about Activation-Free Sulfonyl Fluoride Probes for Fragment Screening In Molecules journal was published the research about synthesis and characterization of a small sulfonyl fluoride library for tagging tractable targets at nucleophilic residues. Based on the results, it was propose that coupling diverse fragments to this warhead would result in a library of sulfonyl fluoride bits (SuFBits), available for screening against protein targets. After in-depth characterization at the surrogate level, SuFBits was successfully applied in labelling of the KRasG12D oncogene mutant, where also was confirmed the functional consequences of the covalent binding. The study was performed by KINETO Lab and collaborative labs in the frame of KRAS Consortium. The publication can be accessed under the following link. PreviousNext

Publication in European Journal of Medicinal Chemistry on covalent fragment mapping of KRasG12C which reveals novel chemotypes with in vivo potency

20/02/2023 Publications Publication in European Journal of Medicinal Chemistry on covalent fragment mapping of KRasG12C which reveals novel chemotypes with in vivo potency As a member of KRAS Consortium, KINETO Lab was big part of the research to identify fragments as suitable starting points targeting KRasG12C, pre-selected in covalent fragment screening of the electrophilic fragment library. Two hits, CFL-120 and CFL-137, confirming their cellular activity against a number of homozygous and heterozygous KRasG12C tumor cells, in comparison to wild type Kras cancerous and non-cancerous cells, were finally tested in vivo using a mouse xenograft model of human lung carcinoma. The fragments demonstrated comparable in vivo efficacy to ARS-1620, the optimized KRasG12C inhibitor which served as a prototype for those molecules that reached the clinic. Our results suggest that CFL-120 and CFL-137 being new specific KRasG12C inhibitor chemotypes demonstrating promising cellular and in vivo efficacy that nominates them for further optimization. The publication can be accessed under the following link. PreviousNext

Published a new study on Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy

10/02/2023 Publications Published a new study on Targeting the Gastrin-Releasing Peptide Receptor (GRP-R) in Cancer Therapy KINETO Lab took a part in development of Bombesin-Based Peptide–Drug Conjugates, acting as drug delivery systems to safely reach the tumour environment. Two of bioconjugates revealed remarkable anti-proliferative activity, an efficient uptake by all three tested human breast and prostate cancer cell lines, high stability in plasma and a prompt release of the drug-containing metabolite by lysosomal enzymes. Moreover, they revealed a safe profile and a consistent reduction of the tumour volume in vivo. The publication can be accessed under the following link. PreviousNext

Published a new study on Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer’s Disease: From In Silico to In Vivo

07/11/2022 Publications Published a new study on Dual Inhibitors of AChE and BACE-1 for Reducing Aβ in Alzheimer’s Disease: From In Silico to In Vivo By applying the computational methods in order to search for dual-inhibitors that could prevent the production of hazardous Aβ42 peptides and avoid their aggregation, it was developed molecules which inhibit AChE and BACE-1 enzymes, while the most potent molecule shows a reduction in brain tissue of soluble Aβ42 in mice. The publication can be accessed under the following link. PreviousNext

Announced publication in Vaccines (Basel) on A Novel C-Type Lectin Receptor-Targeted α-Synuclein-Based Parkinson Vaccine

07/09/2022 Publications Announced publication in Vaccines (Basel) on A Novel C-Type Lectin Receptor-Targeted α-Synuclein-Based Parkinson Vaccine We are pleased to announce that our newest paper in the journal Vaccines (Basel) is now published online. This study provides proof-of-concept for the efficacy of the ‘Win the Skin Immune System Trick’ (WISIT) vaccine technology platform, which induces potent immune responses and therapeutic efficacy in mice, and support further preclinical and clinical development of this vaccine candidate. The publication can be accessed under the following link. PreviousNext