Hansen, Joshua D.; Correa, Matthew; Nagy, Mark A.; Alexander, Matt; Plantevin, Veronique; Grant, Virginia; Whitefield, Brandon; Huang, Dehua; Kercher, Timothy; Harris, Roy; Narla, Rama Krishna; Leisten, Jim; Tang, Yang; Moghaddam, Mehran; Ebinger, Katalin; Piccotti, Joseph; Havens, Courtney G.; Cathers, Brian; Carmichael, James; Daniel, Thomas; Vessey, Rupert; Hamann, Lawrence G.; Leftheris, Katerina; Mendy, Derek; Baculi, Frans; LeBrun, Laurie A.; Khambatta, Gody; Lopez-Girona, Antonia published an article in Journal of Medicinal Chemistry. The title of the article was 《Discovery of CRBN E3 Ligase Modulator CC-92480 for the Treatment of Relapsed and Refractory Multiple Myeloma》.Synthetic Route of C6H13ClN2O3 The author mentioned the following in the article:
Many patients with multiple myeloma (MM) initially respond to treatment with modern combination regimens including immunomodulatory agents (lenalidomide and pomalidomide) and proteasome inhibitors. However, some patients lack an initial response to therapy (i.e., are refractory), and although the mean survival of MM patients has more than doubled in recent years, most patients will eventually relapse. To address this need, we explored the potential of novel cereblon E3 ligase modulators (CELMoDs) for the treatment of patients with relapsed or refractory multiple myeloma (RRMM). We found that optimization beyond potency of degradation, including degradation efficiency and kinetics, could provide efficacy in a lenalidomide-resistant setting. Guided by both phenotypic and protein degradation data, we describe a series of CELMoDs for the treatment of RRMM, culminating in the discovery of CC-92480, a novel protein degrader and the first CELMoD to enter clin. development that was specifically designed for efficient and rapid protein degradation kinetics. In the experiment, the researchers used Methyl 4,5-diamino-5-oxopentanoate hydrochloride(cas: 1323290-64-7Synthetic Route of C6H13ClN2O3)
Methyl 4,5-diamino-5-oxopentanoate hydrochloride(cas: 1323290-64-7) belongs to anime. Reaction with nitrous acid (HNO2), which functions as an acylating agent that is a source of the nitrosyl group (―NO), converts aliphatic primary amines to nitrogen and mixtures of alkenes and alcohols corresponding to the alkyl group in a complex process. This reaction has been used for analytical determination of primary amino groups in a procedure known as the Van Slyke method.Synthetic Route of C6H13ClN2O3
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