AZD3839 is a potent and selective BACE1 inhibitor with about 14-fold selectivity over BACE2. In SH-SY5Y cells, AZD3839 efficiently decreases the Aβ40 levels and decreases the formation of sAPPβ. AZD3839 also decreases the Aβ40 levels secreted from C57BL/6 mouse primary cortical neurons, N2A cells, and Dunkin-Hartley guinea pig primary cortical neurons. AZD3839 causes in vitro BACE1 inhibition in the cell assay with the IC50 value of 16.7 nM. In C57BL/6 mice, AZD3839 (69 mg/kg, p.o.) causes a dose- and time-dependent reduction of plasma and brain Aβ. In guinea pig and non-human primates, AZD3839 also inhibits Aβ generation. AZD3839 has been used in phase I clinical trials studying the basic science of Safety and Tolerability. However future development has been discontinued.

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).

LY2584702 is a potent, highly selective adenosine triphosphate (ATP) competitive inhibitor against p70 S6 kinase, a downstream component of the phosphatidylinositol-3-kinase signalling pathway which regulates cell proliferation and survival. LY2584702 underwent clinical trials against solid tumors both as a monotherapy and in combination with erlotinib or everolimus. No responses were observed for treatment as a single agent. LY2584702 was not well tolerated when administered with erlotinib, therefore this combination is not feasible. The combination with everolimus was better tolerated but yielded very limited clinical benefit.

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.

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.

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.

PTX-008 (OTX008) is a calixarene-based compound and galectin-1 (Gal-1) inhibitor with potential anti-angiogenic and antineoplastic activities. Upon subcutaneous administration, galectin-1 inhibitor OTX008 binds Gal-1 which leads to Gal-1 oxidation and proteosomal degradation through a not yet fully elucidated mechanism, and eventually downregulates Gal-1. This decreases tumor cell growth and inhibits angiogenesis. Gal-1, a multifunctional carbohydrate-binding protein, is often overexpressed on tumor cells and plays a key role in cancer cell proliferation, apoptosis, tumor angiogenesis and evasion of immune responses. PTX-008 had been in phase I clinical trials for the treatment of solid tumours. This compound was originally discovered by University of Minnesota and PepTx, then licensed to OncoEthix (acquired by Merck Sharp & Dohme in 2014). However, no recent developments has been reported.

Pexmetinib (ARRY-614) is a potent, orally bioavailable, dual p38 MAPK/Tie-2 inhibitor with potential antineoplastic, anti-inflammatory and antiangiogenic activities. Pexmetinib inhibited leukemic proliferation, prevented activation of downstream effector kinases and abrogated the effects of TNF-alpha on healthy hematopoietic stem cells. In ex vivo stimulated human whole blood, LPS-induced cytokines was inhibited by Pexmetinib with an IC50 value ranging from 50-120 nM. ARRY-614 inhibited the release of IL-6 from SEA- or LPS-challenged mice with an ED50 value less than 10 mg/kg. Combining Pexmetinib with lenalidomide inhibited both pro-inflammatory cytokines and tumor growth in vivo with higher potency, compared with either agent alone. In dose escalation or expansion cohorts, treatment with Pexmetinib either once daily or twice daily was applied to forty-five patients. Pexmetinib reduced the levels of circulating biomarkers and the p38 MAPK activation of bone marrow.

SP-420 is iron chelator developed by University Of Florida Research Foundation for the treatment of iron overload disease