CPI-0610 is a small molecule inhibitor of the Bromodomain and Extra-Terminal (BET) family of proteins, with potential antineoplastic activity. Upon administration, the BET inhibitor CPI-0610 binds to the acetylated lysine recognition motifs on the bromodomain of BET proteins, thereby preventing the interaction between the BET proteins and acetylated histone peptides. This disrupts chromatin remodeling and gene expression. Prevention of the expression of certain growth-promoting genes may lead to an inhibition of tumor cell growth. CPI-0610 is currently being evaluated in three Phase 1 clinical trials in the U.S.

CRS-3123, also known as REP-3123, is a methionyl-tRNA synthetase inhibitor potentially for the treatment of enteric infections. CRS-3123 is in Phase 1 clinical development for the treatment of Clostridium difficile Infection (CDI). CRS-3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). REP-3123 has been shown to be active in vitro against clinical isolates of C. difficile including epidemic strains such as B1/ NAP1/027; MIC values of REP-3123 for C. difficile are typically 0.5 -- 1.0 mg/l. REP-3123 is also active against a range of clinically important aerobic Gram-positive bacteria including methicillin-susceptible and -resistant Staphylococcus aureus (MIC90 values of 0.06 and 0.25 mg/l, respectively), Streptococcus pyogenes (MIC90 0.5 mg/l) and enterococci (MIC90 32 mg/l). CRS-3123 has numerous potential advantages over current CDI therapies. In addition to being highly potent against all clinical isolates of C. difficile tested, CRS-3123 has several desirable qualities for the treatment of CDI which include: Narrow spectrum for C. difficile, which may substantially reduce the disruption of normal intestinal flora compared to current therapies; Inhibition of toxin production, potentially leading to lower morbidity and mortality; Inhibition of sporulation, potentially leading to lower rates of transmission and recurrence; A novel mechanism of action, which means that its use will not compromise the utility of systemic antibiotics while maintaining activity against pre-existing resistance mechanisms.

JNJ-40411813 (aka ADX71149) is a metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator (PAM) that has the potential to be the first oral non-dopaminergic drug that may address both the positive and negative symptoms of schizophrenia and other indications, such as anxiety. ADX71149 is differentiated from marketed antipsychotics in that it may also show efficacy on negative symptoms and avoid compliance-limiting side effects such as weight gain, hyperprolactinemia and extrapyramidal symptoms, which are associated with the use of dopamine antagonists. The development of ADX71149 is part of a worldwide research collaboration and license agreement between Addex and Janssen Pharmaceuticals, Inc. This drug was also investigated for use as an adjunctive treatment for major depressive disorder (MDD), however, these studies were discontinued. JNJ-40411813 is now in phase II clinical trial for the treatment of epilepsy.

OTS-167 is a maternal embryonic leucine zipper kinase (MELK) inhibitor which demonstrated antitumor properties in laboratory tests. It is being developed as an anti-cancer drug. The compound has been shown to suppress the growth of breast, lung, pancreatic and prostate cancer cells that express high levels of the MELK protein. OTS167 reached phase II clinical trials in patients with AML, ALL, advanced MDSs, advanced MPNs, or advanced CML and phase I in patients with breast cancer.

LY2300559 is a dual metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulator and cysteinyl leukotriene receptor 1 (CysLTR1) antagonist. Eli Lilly was developing LY2300559 for the prevention of migraine. LY2300559 development has been discontinued.

CHF6001 is a phosphodiesterase 4 (PDE4) inhibitor optimised for inhaled delivery and tolerability, for the treatment of Asthma and Chronic Obstructive Pulmonary Disease. CHF6001 was 7- and 923-fold more potent than roflumilast and cilomilast, respectively, in inhibiting PDE4 enzymatic activity. CHF6001 inhibited PDE4 isoforms A-D with equal potency, showed an elevated ratio of high-affinity rolipram binding site versus low-affinity rolipram binding site and displayed >20,000-fold selectivity versus PDE4 compared with a panel of phosphodiesterases. CHF6001 effectively inhibited the release of tumor necrosis factor-α from human peripheral blood mononuclear cells, human acute monocytic leukemia cell line macrophages (THP-1), and rodent macrophages (RAW264.7 and NR8383). CHF6001 has the potential to be an effective topical treatment of conditions associated with pulmonary inflammation, including asthma and chronic obstructive pulmonary disease.

MG-516 (Sitravatinib) is a receptor tyrosine kinase (RTK) inhibitor shown in preclinical models to inhibit a closely related spectrum of RTKs including MET, AXL, MER, and members of the VEGFR, PDGFR, DDR2, TRK and Eph families. Broad-spectrum inhibition of multiple RTK signaling pathways by MGCD516 both in vitro and in vivo results in superior activity compared to imatinib and crizotinib. Clinical trials with MGCD516 is currently undergoing.

PF-3274167 (Cligosiban) is a potent, selective, brain penetrant oxytocin receptor antagonist. Cligosiban interrupts the expulsion phase of ejaculation by reducing the normal bulbospongiosum burst pattern and reducing the expulsions that accompany bursts. Cligosiban represents a promising compound to test the clinical hypothesis that antagonism of central oxytocin receptors may be of therapeutic benefit in the treatment of premature ejaculation. [11C]PF-3274167 is not a suitable tracer for imaging of OTR in rat brain, probably because of a too low affinity for this receptor in addition to a poor brain penetration. PF-3274167 had been in phase I clinical trial for the treatment of sexual function disorders and urinary incontinence. However, this research has been discontinued.

Tirabrutinib (also known as ONO-4059 or GS-4059), a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor that demonstrated antitumor activity in preclinical models. Tirabrutinib participated in phase I clinical trial in patients with relapsed or refractory B-cell malignancies, where it was well tolerated and showed promising efficacy. In addition, tirabrutinib is involved in phase II clinical trials to study safety and efficacy in adults with Active Sjogren's syndrome and in adults with chronic lymphocytic leukemia. Besides the drug was studied for the treatment of Waldenstrom's macroglobulinemia and patients with refractory pemphigus.