2-Iminobiotin (2-IB) is a cyclic guanidino analog of biotin (Vitamin B7) and combined neuronal and inducible (but not endothelial) nitric oxide synthase inhibitor that has been demonstrated to improve neuroprotection in animal models of hypoxic-ischemic Brain Injury. While the exact mechanism of action has yet to be defined, 2-Iminobiotin potentially protects against hypoxic-ischemic brain damage by preventing nitric oxide or peroxynitrite-induced mitochondrial damage. In preclinical models, 2-Iminobiotin provides gender-specific neuroprotection against hypoxia-ischemia in neonatal rats by a NO-independent mechanism.

Tracazolate (ICI 136,753), a pyrazolopyridine, is a non-benzodiazepine with anxiolytic-like activity in animal models. It is known to interact with gamma-aminobutyric acid (GABA)(A) receptors, adenosine receptors, and phosphodiesterases. Its intrinsic efficacy, potentiation, or inhibition is determined by the nature of the third subunit (gamma1-3, delta, or epsilon) within the GABA(A) receptor complex.

CUDC-101 is a multi-targeted agent designed to inhibit epidermal growth factor receptor (EGFR), human epidermal growth factor receptor Type 2 (Her2) and histone deacetylase (HDAC). This drug synergistically blocked key regulators of EGFR/HER2 signaling pathways, also attenuating multiple compensatory pathways, such as AKT, HER3, and MET, which enable cancer cells to escape the effects of conventional EGFR/HER2 inhibitors. Thus, a single compound may offer greater therapeutic benefits, which is verified in clinical trial phase I for the treatment patients with advanced head and neck, gastric, breast, liver, and non-small cell lung cancer tumors. In April 2013, CURIS, INC determined that they would discontinue enrolling patients in phase 1 expansion trial of the intravenous formulation of CUDC-101, and that the future development of CUDC-101 would be dependent on our ability to successfully develop an oral formulation of CUDC-101. However, the efforts to develop an effective oral formulation with improved bioavailability have not resulted in significant improvements when compared to the intravenous formulation of CUDC-101. As a result, at this time CURIS no longer plan to make material investments in this program.

Belnacasan (VX-765), and its active metabolite VRT- 043198, is a novel and irreversible IL-converting enzyme/ caspase-1 inhibitor. VRT-043198 exhibits 100- to 10,000-fold selectivity against other caspase-3, -6 and -9. It exhibited potent inhibition against ICE/caspase-1 and caspase-4 with Ki of 0.8 nM and less than 0.6 nM, respectively. And VRT-043198 also inhibits IL-1β release from both PBMCs and whole blood with IC50 of 0.67 uM and 1.9 uM, respectively. Belnacasan inhibits the release of IL-1, IL-18 and IL-33. Belnacasan has shown to inhibit acute partial seizures in preclinical models and has shown activity in preclinical models of chronic partial epilepsy that do not respond to currently available compounds for epilepsy. In addition, it seems to reduce disease severity and the expression of inflammatory mediators in models of rheumatoid arthritis and skin inflammation. Belnacasan had been in phase II clinical trials by Vertex for the treatment of epilepsy. However, this study has been terminated later.

Dimesone is a synthetic glucocorticoid with anti-inflammatory and anti-allergic activity.

Inflazyme Pharmaceuticals initially developed HT-0712 as a phosphodiesterase IV (PDE4) inhibitor with anti-inflammatory properties. Now the rights on this drug are wholly owned by Dart NeuroScience. January 2015, Dart NeuroScience completed a phase II trial of HT-0712 for the memory disorders, where were evaluated the efficacy in improving memory and cognitive performance.

NPV-LEQ506 is an orally bioavailable small-molecule Smoothened (Smo) antagonist with potential antineoplastic activity. NPV-LEQ506 selectively binds to the Hedgehog (Hh)-ligand cell surface receptor Smo, which may result in the suppression of the Hh signaling pathway, thereby inhibiting tumor cell growth. NPV-LEQ506 is a second-generation inhibitor of smoothened (Smo) with IC50s of 2 and 4 nM in human and mouse, respectively. NPV-LEQ506 has been in clinical trials with Novartis studying the treatment of advanced solid tumors, recurrent or refractory medulloblastoma, and locally advanced or metastatic basal cell carcinoma.

Bristol-Myers Squibb developed BMS-641988 as a nonsteroidal androgen receptor antagonist for the treatment of prostate cancer. BMS-641988 participated in phase I clinical trials in patients with castration-resistant prostate cancer in Japan and in the USA. However, further information is not available.