Saha, Debasmita; Ryan, Katie Rose; Lakkaniga, Naga Rajiv; Smith, Erica Lane; Frett, Brendan published the artcile< Pyrazoloadenine Inhibitors of the RET Lung Cancer Oncoprotein Discovered by a Fragment Optimization Approach>, Safety of 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine, the main research area is pyrazoloadenine inhibitor RET lung cancer oncoprotein fragment optimization; RET inhibitor; fragment-based drug discovery; oncoproteins; pyrazoloadenines.
A fragment-based drug-discovery approach was used on a pyrazoloadenine fragment library to uncover new mols. that target the RET (REarranged during Transfection) oncoprotein, which is a driver oncoprotein in ∼2 % of non-small-cell lung cancers. The fragment library was screened against the RET kinase and LC-2/ad (RET-driven), KM-12 (TRKA-driven matched control) and A549 (cytotoxic control) cells to identify selective scaffolds that could inhibit RET-driven growth. An unsubstituted pyrazoloadenine fragment was found to be active on RET in a biochem. assay, but reduced cell viability in non-RET-driven cell lines (EC50=1 and 3 μM, resp.). To increase selectivity for RET, the pyrazoloadenine was modeled in the RET active site, and two domains were identified that were probed with pyrazoloadenine fragment derivatives to improve RET affinity. Scaffolds at each domain were merged to generate a novel lead compound, 8 p (I), which exhibited improved activity and selectivity for the RET oncoprotein (A549 EC50=5.92 μM, LC-2/ad EC50=0.016 μM, RET IC50=0.000326 μM).
ChemMedChem published new progress about Antitumor agents. 118430-74-3 belongs to class pyrazoles-derivatives, and the molecular formula is C7H11N3, Safety of 3-Cyclopropyl-1-methyl-1H-pyrazol-5-amine.
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics