GSK2879552 – is an orally available, irreversible, inhibitor of lysine specific demethylase 1 (LSD1), with potential antineoplastic activity. Upon administration, GSK2879552 binds to and inhibits LSD1, a demethylase that suppresses the expression of target genes by converting the dimethylated form of lysine at position 4 of histone H3 (H3K4) to mono- and unmethylated H3K4. LSD1 inhibition enhances H3K4 methylation and increases the expression of tumor-suppressor genes. This may lead to an inhibition of cell growth in LSD1-overexpressing tumor cells. LSD1, overexpressed in certain tumor cells, plays a key role in tumor cell growth and survival. On October 2016 GlaxoSmithKline plans a phase I/II trial for Myelodysplastic syndromes (Monotherapy, Combination therapy, Second-line therapy or greater) in USA, Canada and Europe (PO) (NCT02929498).

MK-0359 (L-454560) is a selective and potent type 4 phosphodiesterases (PDE4) inhibitor, which binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. This compound successfully has passed the phase II clinical trial for the treatment of asthma, Pulmonary Disease, Chronic Obstructive (COPD) and Rheumatoid Arthritis. However, there is no information about the further research of this drug.

ASC-J9, also known dimethylcurcumin, is an androgen receptor (AR) degradation enhancer, it suppresses AR function via selective interruption between androgen receptors (ARs) and its selective co-activators (ARA55 or ARA70). This drug was successfully passed phase II clinical trial for topical application to treat the facial acne. In addition, ASC-J9 participated in the preclinical experiments to suppress prostatitis by altering the autoimmune response induced by CD4 T cell recruitment. In combination with sorafenib was shown, that ASC-J9 suppressed the hepatocellular carcinoma (HCC) progression via altering the pSTAT3-CCL2/Bcl2 signals.

Taladegib (LY2940680) is an orally bioavailable small molecule antagonist of the Hedgehog (Hh)-ligand cell surface receptor smoothened (Smo) with potential antineoplastic activity. Taladegib inhibits signaling that is mediated by the Hh pathway protein Smo, which may result in a suppression of the Hh signaling pathway and may lead to the inhibition of the proliferation of tumor cells in which this pathway is abnormally activated. The Hh signaling pathway plays an important role in cellular growth, differentiation and repair; constitutive activation of this pathway is associated with uncontrolled cellular proliferation and has been observed in a variety of cancers. Taladegib has excellent pharmacokinetic properties in rodent and non-rodent species. Taladegib administrated orally treats Ptch+/- p53-/- transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. Taladegib reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and Taladegib induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. Taladegib inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity. Taladegib is currently in phase I clinical trials for ovarian cancer and solid tumours and in phase I/II for esophageal cancer. Ignyta exclusively licensed Taladegib from Eli Lilly and Company in November 2015.

COTI-2 is an orally available small molecule targeting p53, a tumor suppressor gene that is mutated in over 50% of all cancers. The drug was developed by Clinical Outcome Technologies Inc (now Cotinga Pharmaceuticals) and is believed to act by reactivating mutant p53 and inhibiting the phosphatidylinositol 3-kinase (PI3K)/Akt. The drug is being evaluated in phase I clinical trials for the treatment of gynecologic cancers and head and neck squamous cell carcinoma.

Altiratinib, a novel c-MET/TIE-2/VEGFR inhibitor, was able to effectively reduce tumor burden in vivo and block c-MET signaling, cell growth and migration. Altiratinib inhibits not only mechanisms of tumor initiation and progression, but also drug resistance mechanisms in the tumor and microenvironment. Altiratinib durably inhibits MET, both wild-type and mutated forms, in vitro and in vivo. Altiratinib exhibits properties amenable to oral administration and exhibits substantial blood-brain barrier penetration, an attribute of significance for eventual treatment of brain cancers and brain metastases. It is currently in Phase 1 clinical development for the treatment of solid tumors.

DL-Kynurenine is a racemic mixture of D-kynurenine and L-kynurenine. Kynurenine is the precursor of kynurenic acid, an endogenous antagonist of the glycine site of the NMDA (N-methyl-D-aspartate) receptor. Kynurenine has been identified as an endogenous ligand of the aryl hydrocarbon receptor (AhR), a receptor known to be activated by various environmental toxicants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Corticosterone is an adrenocortical steroid, the major glucocorticoid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. Corticosterone is of minor importance in humans but is known, that it has a profound effect on the structure and function of the hippocampus. Brain corticosterone may involve memory storage and emotional stress might cause increases in plasma corticosterone.