Amisulpride, a benzamide derivative, shows a unique therapeutic profile being atypical antipsychotic. At low doses, it enhances dopaminergic neurotransmission by preferentially blocking presynaptic dopamine D2/D3 autoreceptors. At higher doses, amisupride antagonises postsynaptic dopamine D2 and D3 receptors, preferentially in the limbic system rather than the striatum, thereby reducing dopaminergic transmission. In addition its antagonism at serotonin 5-HT7 receptors likely underlies the antidepressant actions. Amisulpride is approved for clinical use in treating schizophrenia in a number of European countries and also for treating dysthymia, a mild form of depression, in Italy.

Cedazuridine is a specific cytidine deaminase (CDA) inhibitor that was approved in combination with decitabine for the treatment of variable forms of myelodysplastic syndrome (MDS). It is known that decitabine is rapidly metabolized by CDA prior to reaching systemic circulation when administered orally. Thus, cedazuridine by inhibition of CDA increases systemic exposure of decitabine.

Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

Berotralstat (ORLADEYO™; BCX7353) is an orally administered kallikrein inhibitor, which has been developed by BioCryst Pharmaceuticals for hereditary angioedema (HAE). The inhibition of kallikrein by berotralstat decreases the production of bradykinin, which prevents the localised tissue oedema that occurs during attacks of HAE. Berotralstat has been approved in the USA, and subsequently in Japan, for prophylaxis to prevent attacks of HAE in adults and paediatric patients aged 12 years or older.

Pralsetinib (GAVRETO™, Blueprint Medicines Corporation) is an orally-administered, next-generation, small-molecule selective rearranged during transfection (RET) inhibitor being developed for the treatment of various solid tumours. RET is a well described proto-oncogene present in multiple cancers including non-small cell lung cancer (NSCLC), papillary thyroid cancer, and medullary thyroid carcinoma. Pralsetinib is a kinase inhibitor of wild-type RET and oncogenic RET fusions (CCDC6-RET) and mutations (RET V804L, RET V804M and RET M918T) with half maximal inhibitory concentrations (IC50s) less than 0.5 nM. In purified enzyme assays, pralsetinib inhibited DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1 at higher concentrations that were still clinically achievable at Cmax. In cellular assays, pralsetinib inhibited RET at approximately 14-, 40-, and 12-fold lower concentrations than VEGFR2, FGFR2, and JAK2, respectively. Pralsetinib is approved for the treatment of RET fusion-positive metastatic NSCLC. In the pivotal phase I/II ARROW trial, pralsetinib demonstrated rapid and durable anti-tumour activity in patients with advanced RET fusion-positive NSCLC who were previously treated with platinum-based chemotherapy or were treatment-naïve. Pralsetinib also showed clinical activity against intracranial metastases arising from NSCLC. Pralsetinib had a manageable tolerability profile, with the most common grade 3 treatment-related adverse events being neutropenia, hypertension, anaemia and decreased white blood cell count.

Pemigatinib, an oral kinases inhibitor, was approved under the brand name PEMAZYRE for the treatment of adults with previously treated, unresectable locally advanced, or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion. The FDA-approved indication for pemigatinib was granted under accelerated approval based on the overall response rate and duration of response in pre-marketing clinical trials. The drug inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplification and fusions that resulted in constitutive activation of FGFR signaling.

L-Acetylleucine is enantiomer of Acetylleucine that used in the treatment of vertigo and cerebellar ataxia. The N-acetyl-L-leucine isomer is the active part of the racemate component since it induces a significant acceleration of the vestibular compensation process similar and even better than that observed under treatment with the racemate component only. Acetylleucine was aggressively marketed in France for vertigo. It may act as a precursor of a peptidic neuromediator responsible for activation of vestibular afferents. It may also have ‘anticalcium’ properties on neurotransmission. Pierre Fabre conducted clinical studies of L-Acetoleusine for Vertigo and Dizzinesstherapy. However, all clinical studies were discontinued

Artenimol (dihydroartemisinin) is a derivate of antimalarial compound artemisinin. Artenimol (dihydroartemisinin) is able to reach high concentrations within the parasitized erythrocytes. Its endoperoxide bridge is thought to be essential for its antimalarial activity, causing free-radical damage to parasite membrane systems including: • Inhibition of falciparum sarcoplasmic-endoplasmic reticulum calcium ATPase, • Interference with mitochondrial electron transport • Interference with parasite transport proteins • Disruption of parasite mitochondrial function. Dihydroartemisinin in combination with piperaquine tetraphosphate (Eurartesim, EMA-approved in 2011) is indicated for the treatment of uncomplicated Plasmodium falciparum malaria. The formulation meets WHO recommendations, which advise combination treatment for Plasmodium falciparum malaria to reduce the risk of resistance development, with artemisinin-based preparations regarded as the ‘policy standard’. However, experimental testing demonstrates that, due to its intrinsic chemical instability, dihydroartemisinin is not suitable to be used in pharmaceutical formulations. In addition, data show that the currently available dihydroartemisinin preparations fail to meet the internationally accepted stability requirements.

Vibegron is a selective beta 3 adrenergic receptor (β3AR) agonist that is being developed in Japan jointly by Kyorin Pharmaceutical Co., Ltd and Kissei Pharmaceutical Co., Ltd and in other regions worldwide (except in several other Asian countries) by Urovant Sciences for the treatment of overactive bladder (OAB). Vibegron potently activates human b3AR and increases cAMP levels, with an EC50 of 1.1 nM. Based on results from Japanese phase III trials, vibegron received approval in Japan in September 2018 for this indication. Vibegron, an active ingredient of Beova® Tablets, is a novel once-daily oral treatment for overactive bladder (OAB), acts selectively on the bladder's β3-adrenergic receptor, relaxes the bladder and enhances the urine collection, and consequently improves the symptoms of urgency, urinary frequency and urge urinary incontinence associated with OAB. On December 23, 2020 the FDA approved vibegron (Gemtesa) for the treatment of adult patients with overactive bladder (OAB) with symptoms of urge urinary incontinence (UUI), urgency, and urinary frequency.

Nifurtimox is a nitrofuran derivative used as a primary agent in the treatment of American trypanosomiasis (Chagas' disease) caused by Trypanosoma cruzi, especially in the acute, early stage of the disease. The efficacy of nifurtimox in the treatment of chronic Chagas' disease varies from one country to another, possibly due to variation in the sensitivity of different strains of the organism. Nifurtimox has also been used to treat African trypanosomiasis (sleeping sickness) and is active in the second stage of the disease (central nervous system involvement). When nifurtimox is given on its own, about half of all patients will relapse, but the combination of melarsoprol with nifurtimox appears to be efficacious. Nifurtimox forms a nitro-anion radical metabolite that reacts with nucleic acids of the parasite causing significant break down of DNA. Nifurtimox undergoes reduction and creates oxygen radicals such as superoxide. These radicals are toxic to T. cruzi. Mammalian cells are protected by the presence of catalase, glutathione, peroxidases, and superoxide dismutase. Accumulation of hydrogen peroxide to cytotoxic levels results in parasite death. Side effects occur following chronic administration, particularly in elderly people. Major toxicities include immediate hypersensitivities such as anaphylaxis and delayed hypersensitivity reaction involving icterus and dermatitis. Central nervous system disturbances and peripheral neuropathy may also occur.