Recently I am researching about P53; INHIBITORS; P53-MDM2; POTENT; DESIGN; ANTAGONISTS; BINDING; DOMAIN; MDMX; CHEMISTRY, Saw an article supported by the National Institute of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) – USA [2R01GM097082-05]; European Lead Factory (IMI) [115489]; Qatar National Research Foundation [NPRP6-065-3-012]; ITN Accelerated Early stage drug dIScovery (AEGIS) [675555]; COFUND ALERT [665250]; Hartstichting (ESCAPE-HF) [2018B012]; KWF Kankerbestrijding grantKWF Kankerbestrijding [10504]; National Science Centre, PolandNational Science Centre, Poland [UMO-2014/12/W/NZ1/00457, UMO-2016/21/D/NZ7/00596]; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) – USANIH National Institute of General Medical Sciences (NIGMS) [R01GM097082] Funding Source: NIH RePORTER. Published in ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER in ISSY-LES-MOULINEAUX ,Authors: Neochoritis, CG; Atmaj, J; Twarda-Clapa, A; Surmiak, E; Skalniak, L; Kohler, LM; Muszak, D; Kurpiewska, K; Kalinowska-Tluscik, J; Beck, B; Holak, TA; Domling, A. The CAS is 100-51-6. Through research, I have a further understanding and discovery of Benzyl Alcohol. Computed Properties of C7H8O
Intrinsically disordered proteins are an emerging class of proteins without a folded structure and currently disorder-based drug targeting remains a challenge. p53 is the principal regulator of cell division and growth whereas MDM2 consists its main negative regulator. The MDM2-p53 recognition is a dynamic and multistage process that amongst other, employs the dissociation of a transient alpha-helical N-terminal lid segment of MDM2 from the proximity of the p53-complementary interface. Several small molecule inhibitors have been reported to inhibit the formation of the p53-MDM2 complex with the vast majority mimicking the p53 residues Phe19, Trp23 and Leu26. Recently, we have described the transit from the 3-point to 4-point pharmacophore model stabilizing this intrinsically disordered N-terminus by increasing the binding affinity by a factor of 3. Therefore, we performed a thorough SAR analysis, including chiral separation of key compound which was evaluated by FP and 2D NMR. Finally, p53-specific anti-cancer activity towards p53-wild-type cancer cells was observed for several representative compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.
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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles