Synthetic molecules for disruption of the MYC protein-protein interface was written by Jacob, Nicholas T.;Miranda, Pedro O.;Shirey, Ryan J.;Gautam, Ritika;Zhou, Bin;de Orbe Izquierdo, M. Elena;Hixon, Mark S.;Hart, Jonathan R.;Ueno, Lynn;Vogt, Peter K.;Janda, Kim D.. And the article was included in Bioorganic & Medicinal Chemistry in 2018.Synthetic Route of C6H8N2O This article mentions the following:
MYC is a key transcriptional regulator involved in cellular proliferation and has established roles in transcriptional elongation and initiation, microRNA regulation, apoptosis, and pluripotency. Despite this prevalence, functional chem. probes of MYC function at the protein level have been limited. Previously, we discovered 5a, that binds to MYC with potency and specificity, downregulates the transcriptional activities of MYC and shows efficacy in vivo. However, this scaffold posed intrinsic pharmacokinetic liabilities, namely, poor solubility that precluded biophys. interrogation. Here, we developed a screening platform based on field-effect transistor anal. (Bio-FET), surface plasmon resonance (SPR), and a microtumor formation assay to analyze a series of new compounds aimed at improving these properties. This blind SAR campaign has produced a new lead compound of significantly increased in vivo stability and solubility for a 40-fold increase in exposure. This probe represents a significant advancement that will not only enable biophys. characterization of this interaction and further SAR, but also contribute to advances in understanding of MYC biol. In the experiment, the researchers used many compounds, for example, 1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1Synthetic Route of C6H8N2O).
1-(1-Methyl-1H-imidazol-2-yl)ethanone (cas: 85692-37-1) belongs to imidazole derivatives. Imidazole is a heterocyclic compound with a five-membered planar ring. It is amphoteric and highly polar. The pharmacophore of imidazole exists in bioactive compounds including amino acids, plant growth regulators and therapeutic agents.n increase of the alkyl chain length of the alcohols. Synthetic Route of C6H8N2O
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem