Discovery and biological evaluation of phthalazines as novel non-kinase TGFβ pathway inhibitors was written by Kharbanda, Anupreet;Zhang, Lingtian;Saha, Debasmita;Tran, Phuc;Xu, Ke;Li, Ming O.;Leung, Yuet-Kin;Frett, Brendan;Li, Hong-yu. And the article was included in European Journal of Medicinal Chemistry in 2021.COA of Formula: C3H9NO The following contents are mentioned in the article:
TGFβ is crucial for the homeostasis of epithelial and neural tissues, wound repair, and regulating immune responses. Its dysregulation is associated with a vast number of diseases, of which modifying the tumor microenvironment is one of vital clin. interest. Despite various attempts, there is still no FDA-approved therapy to inhibit the TGFβ pathway. Major mainstream approaches involve impairment of the TGFβ pathway via inhibition of the TGFβRI kinase. With the purpose to identify non-receptor kinase-based inhibitors to impair TGFβ signaling, an inhouse chem. library was enriched, through a computational study, to eliminate TGFβRI kinase activity. Selected compounds were screened against a cell line engineered with a firefly luciferase gene under TGFβ-Smad-dependent transcriptional control. Results indicated moderate potency for a mol. with phthalazine core against TGFβ-Smad signaling. A series of phthalazine compounds were synthesized and evaluated for potency. The most promising compound I exhibited an IC50 of 0.11 ± 0.02μM and was confirmed to be non-cytotoxic up to 12μM, with a selectivity index of approx. 112-fold. Simultaneously, I was confirmed to reduce the Smad phosphorylation using Western blot without exhibiting inhibition on the TGFβRI enzyme. This study identified a novel small-mol. scaffold that targets the TGFβ pathway via a non-receptor-kinase mechanism. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3COA of Formula: C3H9NO).
2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Because of their lack of hydrogen-bond-donating ability, esters do not self-associate. Consequently, esters are more volatile than carboxylic acids of similar molecular weight.COA of Formula: C3H9NO
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem