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).

PF-477736 is a selective, potent and ATP-competitive Chk1 inhibitor. Compound was tested in combination with gembcitabine in phase I clinical trials in patients with advanced solid tumors.

CX-5461 represents an innovative-targeted agent with numerous differentiating features when compared to current options for treatment of hematologic cancers. CX-5461 is a first-in-class small molecule inhibitor of RNA polymerase I (Pol I) that triggers the nucleolar stress surveillance pathways to activate p53, without causing direct DNA damage. Molecular studies demonstrate that CX-5461 inhibits the initiation stage of rRNA synthesis and induces both senescence and autophagy, but not apoptosis, through a p53-independent process in solid tumor cell lines. Currently, CX-5461 is in clinical trial for patients with advanced hematological malignancies.