MK-8031 (also known as Atogepant) is piperidinonylcarboxamideazaindane derivative patented by Merck Sharp & Dohme Corp as CGRP receptor antagonist useful for prevention and treatment of Migraine. A press release in June 2018 announced positive results for MK-8031, in a Phase 2 trial of daily use for episodic migraine prevention. MK-8031appeared to show good efficacy in migraine prevention and no significant liver toxicity signal at any dose despite daily dosing for 3 months. Phase III clinical trial was initiated in 2019 and currently in progress.

Ibrexafungerp (BREXAFEMME®) is an orally active triterpenoid antifungal drug being developed by SCYNEXIS, Inc. for the treatment of fungal infections. The inhibition of β-1,3-D glucan synthetase by ibrexafungerp compromises the integrity of fungal cell walls. Ibrexafungerp has been recently approved for the treatment of vulvovaginal candidiasis (VVC), and it is the first novel antifungal drug class to be approved in more than 20 years. Food and Drug Administration's decision was based on positive results from two pivotal phase III studies in which oral ibrexafungerp proved both safe and effective in patients with vulvovaginal candidiasis. Development for the treatment of recurrent VVC and invasive fungal infections is ongoing.

Cabotegravir is an investigational drug that is being studied for the treatment and prevention of HIV infection. Cabotegravir belongs to a class (group) of HIV drugs called integrase inhibitors. Integrase inhibitors block an HIV enzyme called integrase. (An enzyme is a protein that starts or increases the speed of a chemical reaction.) By blocking integrase, integrase inhibitors prevent HIV from multiplying and can reduce the amount of HIV in the body. Cabotegravir does not require boosting with an additional drug. Two forms of cabotegravir are being studied: tablets that are taken by mouth (known as oral cabotegravir or oral CAB) and a long-acting injectable form that is injected into the muscle (known as cabotegravir LA or CAB LA; LA stands for "long-acting"). (A long-acting drug formulation works over a long period of time. Using this type of drug might mean that the drug could be taken less often, making a treatment or prevention regimen simpler to take.) Cabotegravir is in Phase-III clinical trials for HIV infections.

KD025 is an orally available, selective small molecule inhibitor of ROCK2 (Rho-associated coiled-coil kinase 2), a molecular target in multiple autoimmune, fibrotic and neurodegenerative diseases. KD025 is the only ROCK2-specific inhibitor in the clinical trials. KD025 down-regulates the IL-17 and IL-21 secretion in human PBMCs, and leads to down-regulation of STAT3 phosphorylation, IRF4, and RORγt expression in CD4+ T cells. Kadmon Pharmaceuticals initiated phase II clinical trials of KD025 for the treatment of Graft-versus-host disease; Idiopathic pulmonary fibrosis; Plaque psoriasis.

AVAPRITINIB (Blu-285) is a potent and selective inhibitor for hematologic malignancies with KIT Exon 17 Mutations. BLU-285 has demonstrated biochemical in vitro activity on the KIT exon-17 mutant enzyme, KIT D816V. Cellular activity of BLU-285 on KIT D816 mutants was measured by autophosphorylation in the human mast cell leukemia cell line HMC1.2, and the P815 mouse mastocytoma cell line with IC50= 4 and 22 nM, respectively. In vivo BLU-285 was well tolerated and has demonstrated dose-dependent antitumor efficacy. Complete tumor growth inhibition and ≥ 75% KIT kinase inhibition was observed with 10 mg/kg once daily, oral dosing of BLU-285 in the aggressive KIT exon 17 mutant driven P815 mastocytoma model grown as a solid tumor allograft as well as in a disseminated model of the disease. BLU-285 was also well tolerated in this in vivo model and had no adverse effects on body weight at either dose.

Lonafarnib is a well-characterized, late-stage, orally active inhibitor of farnesyl transferase, an enzyme involved in modification of proteins through a process called prenylation. It is Investigated for use/treatment in Progeria, Cancer, Hepatitis D. Lonafarnib completely inhibits Rheb prenylation and phosphorylation of S6 ribosomal protein in cell culture, indicating a lack of alternative Rheb prenylation. Other groups have demonstrated that inhibition of protein synthesis via inactivation of eukaryotic elongation factor (eEF2) could be an alternate mechanism of lonafarnib induced growth inhibition that is independent of RAS/p70S6K eEF. Adverse effects included fatigue, diarrhea, dyspnea and neutropenia and respiratory insufficiency.

Relugolix (TAK-385) is an orally active nonpeptide gonadotropin-releasing hormone (GnRH) that binds to human GnRH receptors with subnanomolar affinity. Relugolix was demonstrated to act as a classic competitive antagonist of GnRH binding, but the exact molecular mechanism of that antagonism remains unknown. This drug is being developed as a treatment for various sex hormone related disorders. Based on the phase III HERO trial results, relugolix (Orgovyx) received Food and Drug Administration approval for adult patients with advanced prostate cancer. An oral fixed-dose combination of relugolix/estradiol/norethisterone (also known as norethindrone) acetate (Ryeqo®; Myfembree®) has been approved for the management of heavy menstrual bleeding associated with uterine fibroids in the USA and management of moderate to severe symptoms of uterine fibroids in the EU.

Opicapone (Ongentys®), a potent, oral, third-generation, long-acting, peripheral catechol-O-methyltransferase (COMT) inhibitor, is approved as the adjunctive treatment to levodopa (L-Dopa)/dopa-decarboxylase inhibitor (DDCI) therapy in adults with Parkinson's disease (PD) and end-of-dose motor fluctuations who cannot be stabilized on those combinations. Opicapone is a hydrophilic 1,2,4-oxadiazole analog with a pyridine N-oxide at position 3, with these modifications enhancing its potency and extending its duration of action, whilst avoiding cell toxicity. In preclinical animal studies, Opicapone-induced inhibition of peripheral (but not central) COMT activity was associated with a prolonged increase in systemic and central exposure to L-Dopa, with a corresponding reduction in 3-OMD exposure. Following single or multiple doses of Opicapone (5–1200 mg) in healthy adult volunteers or patients with PD, Opicapone inhibited COMT activity in ex vivo erythrocyte assays in a reversible dose-dependent manner, with the duration of Opicapone-induced COMT inhibition independent of dose. Adjunctive Opicapone was generally well tolerated during more than a year of treatment in BIPARK I and BIPARK II (double-blind plus extension phases). The recommended dosage is 50 mg once daily, which should be taken at bedtime at least 1 h before or after L-Dopa combinations.

Selumetinib (AZD6244 or ARRY-142886) is a potent, selective, and ATP-uncompetitive inhibitor of Ras-Raf-mitogen-activated protein kinase kinase (MEK1/2). This inhibition can prevent ERK activation, disrupt downstream signal transduction, and inhibit cancer cell proliferation and survival. Selumetinib has shown tumour suppressive activity in multiple rodent models of human cancer including melanoma, pancreatic, colon, lung, and breast cancers. AstraZeneca is responsible for development and commercialization of selumetinib.