Provide the optimal solution for your chemistry.
Provide the optimal solution for your chemistry.
In response to Novartis’ publication of TNO155, the Institute for Applied Cancer Science (IACS) at the University of Texas MD Anderson Cancer Center made a significant scientific contribution by unveiling their SHP2 inhibitor, designated as IACS-15414. By employing in silico screening techniques, they utilized the crystal structure of the SHP2 mutant T468 protein (4OHL) as […]
The Discovery of IACS-15414 Read More »
The pharmaceutical market experienced robust growth in 2022, with a total valuation of $758,195 million. This reflects an impressive 8.71% increase compared to the previous year’s market value of $697,430 million. To gain insights into the market leaders based on revenue, an analysis of the top 30 pharmaceutical companies would be showcased as follows. The
The Pharmaceutical Market in 2022 Read More »
Although the rule of 5 has served as a guiding principle for medicinal discovery scientists over the course of decades, it does not confine their exploration to molecules within the physicochemical property space. Protein degraders known as PROTACs, for instance, often possess properties that deviate from Lipinski’s rule, which characterizes molecules considered suitable for drug
Protein Degraders in Clinical Trials Read More »
The first clinical-stage SHP2 (Src homology-2 domain-containing protein tyrosine phosphatase-2) inhibitor TNO155 was discovered by Novartis. The intriguing details of this discovery were documented in two consecutive papers, namely J. Med. Chem. 2016, 59, 7773−7782 and J. Med. Chem. 2020, 63, 13578−13594. During a high-throughput screening process, a known ion channel inhibitor SHP836 was identified
A significant number of interventional and observational clinical trial records, totaling more than 790, are associated with either KRAS itself or the pathway in which KRAS is involved. These meticulously designed interventional studies serve the purpose of evaluating potential treatments for cancers, including vaccines, monoclonal antibodies, and small molecules. Notably, there exist more than 22
Synthesis/Isolation of Atropisomers Read More »
There are 790+ interventional and observational clinical trial records associated with either KRAS itself or the pathway that KRAS is part of. The interventional studies are designed to evaluate the potential treatments including small vaccines, monoclonal antibodies and small molecules. More than 22 small molecule inhibitors with varied specificity against distinct KRAS mutants.
Since Novartis published the first SHP2 allosteric inhibitor SHP099 in 2016, the discovery of other SHP2 inhibitors has ignited explosively. By May 2023, more than 14 SHP2 inhibitors are under clinical trials. The disclosed structures of several SHP2 inhibitors, besides Novartis’ clinical candidate TNO155, indicate that they have adopted SHP099 as the lead compound.
SHP2 Inhibitors in Clinical Trials Read More »
TNO155, a clinical-stage SHP2 inhibitor, was synthesized using a divergent approach employing building blocks 11 and 12 with the longest linear sequence of 9 steps. The chiral methyl group in the spiro-ring of 11 was obtained from a chiral pool starting material, L-Lactide 3, while the chiral amine was generated through diastereoselective hydrogenation of oxime
The Process Chemistry of TNO155 Read More »