IPI-549 is an orally bioavailable, highly selective small molecule inhibitor of the gamma isoform of phosphoinositide-3 kinase (PI3K-gamma) with potential immunomodulating and antineoplastic activities. Upon administration, IPI-549 prevents the activation of the PI3K-gamma-mediated signaling pathways, which may lead to a reduction in cellular proliferation in PI3K-gamma-expressing tumor cells. In addition, this agent is able to modulate anti-tumor immune responses and inhibit tumor-mediated immunosuppression. Unlike other isoforms of PI3K, the gamma isoform is overexpressed in certain tumor cell types and immune cells; its expression increases tumor cell proliferation and survival. By selectively targeting the gamma isoform, PI3K signaling in normal, non-neoplastic cells is minimally or not affected, which results in a reduced side effect profile. Preclinical data in multiple solid tumor models have demonstrated that IPI-549 targets immune cells and alters the immune-suppressive microenvironment, promoting an anti-tumor immune response that leads to tumor growth inhibition. A Phase 1 study of IPI-549 in patients with advanced solid tumors is ongoing.

Teprotide, a nonapeptide isolated from the venom of a Brazilian pit viper, Bothrops jararaca, was the first angiotensin converting enzyme (ACE) inhibitor to be discovered and tested. It was found to be an effective, non-toxic antihypertensive agent as well as an afterload-reducing agent for patients with congestive heart failure (CHF). The primary activity of teprotide resulted from blockade of the angiotensin I converting enzyme--the pivotal step in the renin-angiotensin-aldosterone system (RAAS), and consequent reductions in angiotensin II levels. There was limited clinical testing for teprotide because of: its scarcity; the need for parenteral administration; and the subsequent discovery and synthesis of captopril, the first orally active angiotensin converting enzyme inhibitor.

N-acetylmannosamine (ManNAc), a hexosamine monosaccharide, is the first committed biological precursor of Neu5Ac. N-acetylmannosamine is being investigated as a potential treatment for GNE myopathy. N-acetylmannosamine has being reported to improve the cognitive function in aged animals. It has potential therapeutic application for cognitive dysfunction. N-acetylmannosamine is under investigation for GNE myopathy.

Ceralasertib, previously known as AZD6738, a potent and selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase was developed as an anticancer agent. Prevention of ATR-mediated signaling leads to the inhibition of DNA damage checkpoint activation, disruption of DNA damage repair, and the induction of tumor cell apoptosis. AZD6738 as a combination therapy participates in phase II clinical trials for the treatment of gastric adenocarcinoma and malignant melanoma (in combination with durvalumab). For the treatment of gastric and breast cancer in combination with carboplatin, or with olaparib or with MEDI4736. Combination of acalabrutinib and AZ6738 is used in phase II trials for patients with chronic lymphocytic Leukemia. Besides, AZD6738 participates in umbrella Phase II study in patients with metastatic non-small cell lung cancer (NSCLC) who have progressed on an anti-programmed cell death-1/anti-programmed cell death ligand 1 (anti-PD-1/PD-L1) containing therapy.

GNE0877, aminopyrazole derivative, is a highly potent, selective, brain-penetrable LRRK2 inhibitor and an investigational drug for Parkinson's disease therapy. It inhibits LRRK2 Ser1292 autophosphorylation in BAC transgenic mice expressing human LRRK2 protein with the G2019S Parkinson’s disease mutation with an IC50 value of 3 nM in vivo. GNE0877 demonstrated metabolic stability, good oral bioavailability (88%) and brain penetration across multiple species.