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.

Pafuramidine or DB289, [2,5-bis-(4-amidinophenyl)furan bis-O-methylamidoxime] is a pro-drug of DB75, [2,5-bis(4-amidinophenyl)furan] also known as furamidine. The biotransformation process of DB289 to DB75 in the human liver consists of three O-demethylation reactions catalyzed by the Cyp4F enzyme subfamily and three N-dehydroxylation reactions catalyzed by cytrochrome b5 and NADH-cytochrome b5 reductase. DB289 was studied for therapeutic treatment against human African trypanosomiasis, Pneumocystis pneumonia and malaria. In November 2006, Immtech Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) had granted orphan drug designation for pafuramidine (DB289) to treat Pneumocystis jiroveci pneumonia (PCP), a common life-threatening opportunistic infection in HIV/AIDS and other immunosuppressed patients. Despite the high efficacy of DB289 in patients, the mechanism of action of DB75 is unknown. The mechanism of antimicrobial activity of diamidine compounds is incompletely understood. They undergo active uptake by purine transporter systems in trypanosomes and their mechanism of action may involve interference with DNA-associated enzymes inhibition of heme crystallization11 or/and collapse of the transmitochondrial membrane potential.

CBL0137 (also known as Curaxin CBL0137) is a metabolically stable curaxin and belongs to the class of small molecules with anti-cancer activity. CBL0137 is in Phase I clinical trials to treat hematological malignancies and solid tumors. CBL0137 binds to Facilitates Chromatin Transcription (FACT) and sequesters the FACT complex on chromatin, which inhibits its activity. This prevents transcription of certain genes involved in cancer-associated signaling pathways; it specifically inhibits the transcription of both NF-kappa β and heat shock transcription factor 1 (HSF1) and simultaneously activates p53. In addition, CBL0137 was investigated in vitro and in models mice for pancreatic ductal adenocarcinoma (PDA) and the obtained data suggested testing of CBL0137 efficacy in Phase II trial in PDA patients alone and in combination with gemcitabine.

Pinocembrin (5,7-dihydroxyflavanone) is one of the primary flavonoids isolated from the variety of plants, mainly from Pinus heartwood, Eucalyptus, Populus, Euphorbia, and Sparattosperma leucanthum. Pinocembrin is a major flavonoid molecule incorporated as multifunctional in the pharmaceutical industry. Its vast range of pharmacological activities has been well researched including antimicrobial, anti-inflammatory, antioxidant, and anticancer activities. In addition, pinocembrin can be used as neuroprotective against cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antiexcitotoxic effects.