AZ-1080 (AZD-1080) is an inhibitor of GSK-beta which was developed by AstraZeneca and initially tested in patients with Alzheimer’s disease (phase I). The drug was discontinued for the aforementioned condition, but now it is being investigated as a potential therapy for ovarina cancer and emdometrial carcinoma (basic research).

JTC 801 was developed by Japan Tobacco as a novel opioid receptor-like1 (ORL(1)) receptor antagonist. It was found, that JTC-801 completely antagonized the suppression of nociceptin on the forskolin-induced accumulation of cyclic AMP using ORL(1) receptor expressing HeLa cells in vitro. JTC 801 produced analgesic effects and was studied in phase II of a clinical trial for the treatment of neuropathic, cancer and postoperative pain. Nevertheless, that studies were discontinued.

SB-271046 is one of the first selective 5-HT6 receptor antagonists to be discovered. SB-271046 is a potent, selective and orally active 5-HT6 receptor antagonist with a pKi value of 8.9. This compound provides a useful tool for further elucidating the physiological function of 5-HT6 receptors in vivo. SB-271046 was found to increase levels of the excitatory amino acid neurotransmitters glutamate and aspartate, as well as dopamine and noradrenaline in the frontal cortex and hippocampus of rats, and 5-HT6 antagonists have been shown to produce nootropic effects in a variety of animal studies. Suggested applications of SB-271046 included treatment of schizophrenia and other psychiatric disorders. A phase I clinical development of SB-271046 by GlaxoSmithKline (GSK) was discontinued due to a poor BBB permeability.

PD-153035 is a potent and selective ATP-competitive inhibitor of the epidermal growth factor receptor tyrosine kinase EGFR. PD 153035 shows a potent and selective inhibitory effect on tyrosine phosphorylation induced by EGF in Swiss 3T3 fibroblast and A-431 human epidermoid carcinoma cells. PD153035 shows dose-dependent growth inhibitory effects in cultures of EGF receptor-overexpressing human cancer cell lines (A431, Difi, DU145, MDA-MB-468, and ME180) and in nasopharyngeal carcinoma (NPC) cell lines (NPC-TW01, NPC-TW04, and HONE1). Pretreatment of EGFR inhibitors by 24 hours significantly enhances the cytotoxic effect of doxorubicin, paclitaxel, cisplatin, and 5-fluorouracil in NPCTW04 cells. PD153035 abolishes COX-2 expression induced by the PAR(2)-activating peptide 2-furoyl-LIGRLO-NH(2) (2fLI) in Caco-2 colon cancer cells. In A431 human epidermoid tumors grown as xenografts in immunodeficient nude mice, PD153035 at 80 mg/kg i.p. inhibit EGF receptor tyrosine kinase activity. PD153035 improves glucose tolerance, insulin sensitivity, and signaling and reduces subclinical inflammation in HFD-fed mice.

Omidenepag isopropyl, a prodrug, is hydrolyzed in the eye to the active form (Omidenepag) which functions as a selective, nonprostaglandin, prostanoid EP2 agonist, has been developed by Ube Industries and Santen Pharmaceutical as an ophthalmic solution (EYBELIS®) for the treatment of glaucoma and ocular hypertension. Omidenepag isopropyl increases the outfow of aqueous humor via both the uveoscleral outfow and the trabecular outfow pathways, resulting in potent and stable reduction in intraocular pressure (IOP). In September 2018, omidenepag isopropyl ophthalmic solution 0.002% was approved in Japan for the treatment of glaucoma and ocular hypertension. On September 22, 2022, the FDA approved Santen’s Omlonti (omidenepag isopropyl), for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.

Mobocertinib (EXKIVITY™) is a first-in-class EGFR tyrosine kinase inhibitor being developed for the treatment of EGFR exon 20 insertion (EGFRex20ins) -positive non-small cell lung cancer (NSCLC). Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR exon 20 insertion mutations at lower concentrations than wild type (WT) EGFR. Two pharmacologically-active metabolites (AP32960 and AP32914) with similar inhibitory profiles to mobocertinib have been identified in the plasma after oral administration of mobocertinib. In vitro, mobocertinib also inhibited the activity of other EGFR family members (HER2 and HER4) and one additional kinase (BLK) at clinically relevant concentrations (IC50 values <2 nM). Based on efficacy in patients whose disease had progressed on or after platinum-based therapy in a phase I/II trial, mobocertinib was recently granted accelerated approval in the USA in this indication. The drug is also being assessed for marketing approval in various other countries and territories including the EU and China.

Umbralisib (Ukoniq, TG Therapeutics) is an orally available PI3K delta inhibitor, targeting the delta isoform with nanomolar potency and several fold selectivity over the alpha, beta, and gamma isoforms of PI3K. The delta isoform of PI3K is strongly expressed in cells of hematopoietic origin and is believed to be important in the proliferation and survival of B-cell lymphocytes. On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib for the following indications: adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen; adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy. However, on June 1, 2022, the FDA withdrew its approval for the cancer medicine Ukoniq due to safety concerns.

Rifamycin SV is a derivative of antibiotic rifamycin B (the natural fermentation product of S. mediterranei broths). The primary target of rifampicin on whole bacteria is the synthesis of RNA. Rifamycin belongs to the ansamycin class of antibacterial drugs and acts by inhibiting the beta subunit of the bacterial DNA-dependent RNA polymerase, blocking one of the steps in DNA transcription. This results in inhibition of bacterial synthesis and consequently growth of bacteria. Rifampicin exhibits bactericidal activity on Gram-positive and Gram-negative bacteria and on mycobacteria. Rifamycin SV MMX® (AEMCOLO), a non-absorbable rifamycin antibiotic formulated using the multi-matrix system, was designed to exhibit its pharmacological action on the distal small intestine and colon. AEMCOLO is indicated for the treatment of travelers’ diarrhea (TD) caused by non-invasive strains of Escherichia coli in adults.

Betrixaban is an anticoagulant drug which acts as a direct factor Xa inhibitor. Betrixaban is now being developed by Portola Pharmaceuticals. Oral, once-daily Factor Xa inhibitor anticoagulant that directly inhibits the activity of Factor Xa, an important validated target in the blood coagulation pathway, to prevent life-threatening thrombosis. U.S. Food and Drug Administration granted Fast Track designation to betrixaban for extended-duration prevention of venous thromboembolism (VTE; blood clots) in acute medically ill patients (i.e., those who are hospitalized for serious medical conditions, such as heart failure, stroke, infection and pulmonary disease). Has the potential to become the first oral Factor Xa inhibitor anticoagulant approved for hospital-to-home prevention of VTE in acute medically ill patients.

Copanlisib, developed by Bayer, is a phosphoinositide 3-kinase (PI3K) inhibitor with potential antineoplastic activity. Copanlisib inhibits the activation of the PI3K signaling pathway, which may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis and dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents. Copanlisib is currently under Phase II/III clinical trials for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia.