Rimiducid (AP1903) is a lipid-permeable tacrolimus analogue with homodimerizing activity. Rimiducid homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val). This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered proteins such as the iCD40 receptor, Fas intracellular domain or iCaspase 9 resulting in downstream signaling activation during cell therapy. Orphan designation was granted for rimiducid (AP1903) for the treatment of graft-versus-host disease.

Rapastinel (formerly known as GLYX-13) is an investigational intravenous formulation of a novel NMDA receptor partial agonist, which is being evaluated for adjunctive treatment of Major depressive disorder, and has shown a rapid onset of antidepressant efficacy 1 day after a single dose in a Phase 2 clinical trial of patients with Major depressive disorder who had an inadequate response to one or more antidepressants. No psychotomimetic or hallucinogenic side effects were observed with rapastinel. Few adverse events were reported by 5% or more of subjects and these were rated as mild or moderate. These included headache, somnolence, dizziness, dysgeusia, and fatigue. On January 29, 2016, Allergan (who acquired Naurex in July 2015) announced that rapastinel had received Breakthrough Therapy designation from the U.S. FDA for adjunctive treatment of major depressive disorder.

Rigosertib sodium (ON 01910.Na) is a small molecule inhibitor of critical pathways important in the growth and survival of cancer cells, being developed by Onconova Therapeutics ("Onconova") for the treatment of hematologic malignancies and solid tumors. Rigosertib (ON-01910) is a non-ATP-competitive inhibitor of PLK1 with IC50 of 9 nM in a cell-free assay. It shows 30-fold greater selectivity against Plk2 and no activity to Plk3. Extensive Phase I and Phase II studies with rigosertib have been conducted at leading institutions in the U.S. and abroad in more than 450 patients with solid tumors and hematological cancers, including MDS and AML. MDS and AML are blood disorders widely recognized as difficult to manage, with limited therapeutic options available for patients, especially those with drug-resistant disease. The multi-site Phase III ONTIME trial in MDS patients is under a Special Protocol Assessment (SPA) from the U.S. FDA and is being supported by an award from the Therapeutics Acceleration Program (TAP) of the Leukemia and Lymphoma Society (LLS). FDA has granted Orphan Drug Designation for the use of rigosertib in MDS. The clinical program in solid tumors is also advancing with initiation of the Phase II/III combination ONTRAC trial (ON 01910.Na TRial in Patients with Advanced Pancreatic Cancer) and Phase II single agent trial in ovarian cancer. In Japan, SymBio is developing rigosertib for the treatment of refractory/relapsed HR-MDS (IV form) and first-line LR-MDS (oral form).

Rebastinib (DCC-20) is a TIE2 kinase inhibitor currently in Phase 1 clinical development to treat breast cancer and Chronic Myeloid Leukemia. Rebastinib potently inhibited TIE2 kinase in cellular assays and blocked primary tumor growth by 75% as a single agent and by 90% in combination with the standard chemotherapeutic agent paclitaxel. Furthermore, rebastinib therapy significantly reduced the presence of tumor-promoting macrophages in tumor biopsies by 80%. This blockade of tumor macrophages correlated with inhibition of breast cancer lung metastases.

Miransertib (ARQ 092) is a selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms. Miransertib binds inactive AKT, preventing membrane localization and subsequent AKT activation, and binds active AKT, resulting in direct inhibition. Miransertib participates in Phase 1/2 of clinical trials to treat patients at least 2 years of age with PIK3CA-related Overgrowth Spectrum (PROS) and Proteus syndrome (PS). In addition, the drug is involved in the phase I trial in patients with lymphoma, endometrial cancer, and AKT1 E17K mutations. Recently was shown that miransertib could be an excellent lead compound for the development of new oral drug therapy for visceral and cutaneous leishmaniasis.

PF-04531083 is selective Nav1.8 blocker. It has been investigated for the treatment of chronic pain, heart pain, post-surgical dental pain. However, these trials were discontinued.

AZD-4547 is an orally bioavailable inhibitor of the fibroblast growth factor receptor (FGFR) with potential antineoplastic activity. FGFR inhibitor AZD4547 binds to and inhibits FGFR, which may result in the inhibition of FGFR-related signal transduction pathways, and, so, the inhibition of tumor cell proliferation and tumor cell death. FGFR, up-regulated in many tumor cell types, is a receptor tyrosine kinase essential to tumor cellular proliferation, differentiation and survival. AZD-4547 is a selective FGFR inhibitor targeting FGFR1/2/3 with IC50 of 0.2 nM/2.5 nM/1.8 nM in cell-free assays, weaker activity against FGFR4, VEGFR2 (KDR), and little activity observed against IGFR, CDK2, and p38. Compared to FGFR1-3, AZD-4547 displays weaker activity against FGFR4 with IC50 of 165 nM. AZD-4547 only inhibits recombinant VEGFR2 (KDR) kinase activity with IC50 of 24 nM, in the in vitro selectivity test against a diverse panel of representative human kinases. AZD-4547 is under clinical investigation for the treatment of FGFR-dependent tumors. It is in phase II clinical studies for the treatment of breast cancer; gastric cancer; lung cancer; oesophageal cancer and in phase II/III clinical studies for the treatment of non-small cell lung cancer.

GKT137831, a novel pyrazolopyridinedione derivative, a dual inhibitor of NADPH oxidases (NOX) 1 and NOX4, reduces inflammation in the ischemic retina by dampening the pro-inflammatory phenotype of retinal immune cells as well as macroglial Müller cells and neurons. In patients with diabetic kidney disease, GKT137831 demonstrated an excellent safety profile and statistically significant reduction in both liver enzyme and inflammatory marker levels in multiple phase I and phase II clinical studies. GKT137831 may be of significant benefit for patients with systemic sclerosis as studies in experimental models show that the compound may reduce the abnormal growth of connective tissue (fibrosis) and improve survival. GKT137831 was granted Orphan Drug designation for the treatment of systemic sclerosis from the FDA and the EMA. GKT-137831 acts as a Nox4 and Nox1 inhibitor ((Ki 100–150 nM). GKT-137831 attenuates hypoxia-induced pulmonary vascular cell proliferation. Also a potent inhibitor of fibrosis and hepatocyte apoptosis.