Emetine Hydrochloride is the chloride salt of a white crystalline bitter alkaloid isolated from the root of the plant Psychotria Ipecacuanha (ipecac root)Uragoga (or Cephaelis) ipecacuanha or U. acuminata, of the Rubiaceae with antiemetic and anthelminthic properties. Emetine inhibits protein synthesis in eukaryotic (but not prokaryotic) cells. It inhibits SARS-CoV2, Zika and Ebola virus replication. Agents that cause vomiting isolated ein 1817 par Pelletier and Magendie. The structure elucidated in 1948. Emetine hydrochloride CAS-14198-59-5 (CID 6603320) ML081 represents the first non-covalent, selective RBBP9 inhibitor but moderate IC50 8 microM
The retinoblastoma (RB) tumor suppressor protein controls cell cycle progression by regulating the activity of the transcription factor E2F, which activates genes essential for DNA replication. Thus, factors that bind and regulate RB activity are considered valuable targets for preventing tumorigenesis. The enzyme RB binding protein 9 (RBBP9) is widely expressed in different tissues and upregulated in certain tumors. As a result, the identification of compounds that selectively inhibit RBBP9 activity would serve as potentially valuable probes for the study of apoptosis, cell cycle, and tumorigenesis. We previously reported a modestly potent, RBBP9 reversible inhibitor, ML081 (CID-6603320). However, ML081 exhibits high cytotoxicity. We, therefore, have now identified a newer probe, ML114 (CID-5934766), which is 10-fold more potent than ML081, exhibits no cytotoxicity, and is from an entirely different structural and mechanistic class of compounds that covalently inhibit RBBP9. This new probe will be useful for in vitro assays in which it is desirable to specifically block RBBP9 activity for primary research purposes.
The retinoblastoma (RB) tumor suppressor protein controls cell cycle progression by regulating the activity of the transcription factor E2F, which in turn activates genes essential for DNA replication. Thus, factors that bind and regulate RB activity provide for valuable targets for preventing tumorigenesis. The enzyme, RB binding protein 9 (RBBP9), is widely expressed in a number of different tissues and is upregulated in certain tumors. As a result, the identification of compounds that selectively inhibit RBBP9 activity would serve as potentially valuable probes for the study of apoptosis, cell cycle, and tumorigenesis. The probe ML081 (CID- 6603320; emetine hydrochloride) represents the first non-covalent, selective RBBP9 inhibitor, and will be useful for exploring the enzymatic functions of RBBP9 in biological systems. Moreover, the tight structure-activity relationship of the emetine-RBBP9 interaction suggests that only minor modifications to the emetine structure will improve its activity. As a result, future studies will involve semi-synthetic addition of small moieties to the emetine and cephaeline scaffolds.
