China
Africa
Explore chapters and articles related to this topic
Naturally Occurring Histone Deacetylase (HDAC) Inhibitors in the Treatment of Cancers
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Sujatha Puttalingaiah, Murthy V. Greeshma, Mahadevaswamy G. Kuruburu, Venugopal R. Bovilla, SubbaRao V. Madhunapantula
Benzamides are another class of HDAC inhibitors synthesized and tested against several carcinomas (Eckschlager et al., 2017). Although benzamides are primarily produced by chemical synthesis, a brief note on this group is provided as a part of this chapter to highlight the importance of this class of HDAC inhibitors in developing potent anti-cancer agents. Earlier studies have demonstrated that benzamide type HDAC inhibitors are relatively non-toxic (compared to hydroxamates) and more specifically target a particular class of HDAC enzymes (Chou et al., 2008). For example, a study showed that pimelic diphenylamide specifically inhibits Class I HDAC, with no demonstrated activity against Class II HDACs (Chou et al., 2008). Among Class I HDACs, benzamide inhibitor R106 inhibited HDAC3 with 15 times lower inhibitor constant compared to HDAC1 (Chou et al., 2008). Similarly, many other benzamide type inhibitors were synthesized and tested against multiple cancers (Abdizadeh et al., 2017).
Electrophysiological Studies of 5-Hydroxytryptamine Receptors on Enteric Neurons
Published in T.S. Gaginella, J.J. Galligan, SEROTONIN and GASTROINTESTINAL FUNCTION, 2020
The substituted benzamides cisapride and renzapride can block depolarizations caused by 5-HT acting at 5-HT1P receptors and have been reported to be antagonists of the 5-HT1P receptor.40,41 However, there are limitations to the use of the substituted benzamides as selective 5-HT1P receptor antagonists. Cisapride blocks fast and slow depolarizations caused by 5-HT in myenteric AH neurons, but the specificity of cisapride for 5-HT responses was not established in this study.40 Furthermore, it was also shown that cisapride blocks presumably cholinergic fEPSPs recorded from myenteric neurons, an effect attributed to a presynaptic action of cisapride.40 Renzapride (1 μM) also blocks slow depolarizations caused by 5-HT, but even 10-fold higher concentrations of renzapride have little effect on the fast 5-HT response.41 Depolarizations caused by ACh or substance P are not affected by renzapride, indicating renzapride does not block ACh or substance P receptors or the effector ion channels or intracellular signal transduction processes mediating slow depolarizations. These data suggest that renzapride may be an effective 5-HT1P receptor antagonist. However, in radioligand binding studies, renzapride does not displace 5-HT or 3H-5-HTP-DP from enteric membranes, indicating that renzapride does not interact with the 5-HT binding site directly but may act at a “benzamide” binding site associated with the 5-HT1P receptor.41
Psychopharmacology EMIs
Published in Michael Reilly, Bangaru Raju, Extended Matching Items for the MRCPsych Part 1, 2018
Each option may be used once, more than once or not at all.For each of the following statements about adverse effects of antipsychotics, choose the drug above that is most likely to be implicated.A common side-effect of this thienobenzodiazepine atypical antipsychotic is weight gain.This dibenzothiazepine atypical antipsychotic is not associated with any significant increase in serum prolactin levels.This substituted benzamide antipsychotic is thought to have a dose-dependant action at presynaptic dopamine sites.This diphenylbutylpiperidine is the longest-acting per oral administered antipsychotic.
Development and characterisation of levosulpiride-loaded suppositories with improved bioavailability in vivo
Published in Pharmaceutical Development and Technology, 2019
Levosulpiride is a derivative of benzamide group which is potentially used for the treatment of depression and psychiatric problems. It selectively blocks D2 receptors in submucosal and myoenteric plexus (Kim et al. 2016a; Fotaki et al. 2005). Levosulpiride enhances gastric evacuation and digestive signs in patients with functional dyspepsia and diabetic gastroparesis. Moreover, it has been successfully investigated for the treatment of premature ejaculation (Greco et al. 2002; Hussain et al. 2010). Beside all the related efficacy of levosulpiride, its poorly water solubility and low permeability (BCS Class IV drug) is a big challenge in developing various formulations, including oral and injectable formulations, for its therapeutic use (Ibrahim et al. 2013). Furthermore, because of its low pKa, various excipients are required for the development of injectable formulations, which sometimes results in severe pain to the patient leading to discomfort, after injection.
HDAC inhibitors: a 2013–2017 patent survey
Published in Expert Opinion on Therapeutic Patents, 2018
Micaela Faria Freitas, Muriel Cuendet, Philippe Bertrand
Despite these limitations, most of the 105 clinical trials published during the last four years (clinicaltrials.gov website portal with keywords HDAC inhibitors and (industry, others)) involved hydroxamates such as vorinostat (22% of this patent review) or panobinostat (18%). Benzamides are also still used such as entinostat (18%), mocetinostat (6%), and chidamide (5%). Only few clinical trials involve new compounds with undisclosed structures, such as ‘FRM-0334’ or ‘KA2507’. The most important therapeutic application remains cancer (43%), with specific forms such as leukemia (9%), lymphoma (15%), and multiple myeloma (9%). Infectious diseases represent 10% of the trials (HIV, mycosis) and neurological disorders only 4%. The majority of clinical studies are in Phase 1 (33%) and Phase 2 (34%) and 22% involving both Phase 1 and Phase 2. Phase 3 trials represent 4% and Phase 4 only 1%, implying that Phase 3 studies seem currently difficult to reach.
Zinc binding groups for histone deacetylase inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Lei Zhang, Jian Zhang, Qixiao Jiang, Li Zhang, Weiguo Song
Benzamide derivatives are a big class of HDACIs with superior class I selectivity compared with hydroxamic acid HDACIs. The crystal structure analysis revealed chelation of the zinc ion by the amino group in the benzamide. Additionally, the distance between the carbonyl oxygen and zinc is more than 2.5 Å, indicating weak interactions. Chidamide (Epidaza)27 is a benzamide HDACI approved by Chinese Food and Drug Administration (CFDA) for the treatment of relapsed or refractory PTCL (Figure 4). MS-27528–31 (HDAC1 selective) and MGCD010332–36 (HDAC1, 2 selective) are two benzamide HDACIs designed for the treatment of both hematologic malignancies and solid cancers, which are currently in clinical trial as mono therapies or in combination with other drugs. Good performances in clinical trials were also observed for another benzamide derivative, CI99437–40.