GDC-0994 (RG7842) is a selective inhibitor of ERK1/2, also known as extracellular-signal-regulated kinases. Daily, oral dosing of GDC-0994 results in significant single-agent activity in multiple in vivo cancer models, including KRAS-mutant and BRAF-mutant human xenograft tumors in mice. GDC-0994 neither increases nor decreases phospho-ERK, suggesting that different ERK inhibitors have alternative mechanisms of action with respect to feedback signaling. GDC-0994 is currently advancing in a Phase 1 trial in patients with solid tumors.

Vivolux developed VLX-1570 as a small molecule proteasome 19S proteasome deubiquitinase (DUB) inhibitor. In addition, VLX1570 shows selectivity for ubiquitin-specific protease-14 and induces apoptosis of multiple myeloma cells. VLX-1570 participated in phase I/II clinical trial in patients with myeloma. However, this study was terminated because of the dose-limiting toxicity was observed. Thus, the full clinical trial was put on hold. VLX1570 also inhibits ubiquitin carboxyl-terminal hydrolase isozyme L5 (UCHL5). Besides, was shown that VLX1570 modulated bio-cellular pathways that were essential for Waldenstrom macroglobulinemia (WM) cell survival. Thus, VLX1570 can be further studied for clinical use in patients with WM.

Echinomycin is a cyclic peptide of the family of quinoxaline antibiotics that was originally isolated from Streptomyces echinatus. It is thought to act as a bifunctional DNA intercalator. Echinomycin has a binding site size of four base pairs. The strong binding sites for echinomycin contain the central two-base-pair sequence 5'-CG-3'. Echinomycin interferes with HIF-1 DNA binding in a sequence-specific fashion. It was brought into clinical trials by the NCI 20 years ago based on its antitumor activity. It has been extensively tested in phase I-II clinical trials. Nausea, vomiting, reversible liver enzyme abnormalities, and allergic reactions were the most common toxicities encountered. However, minimal or no antitumor activity was found in phase II clinical trials.

EW-7197 is an orally bioavailable inhibitor of the serine/threonine kinase, transforming growth factor (TGF)-beta receptor type 1 (TGFBR1), also known as activin receptor-like kinase 5 (ALK5), with potential antineoplastic activity. EW-7197 is in phase I clinical trials for the treatment of solid tumors. Also, EW-7197 has a strong potential as an anti-fibrosis therapeutic agent.

Praziquantel, (-)- is oxopyrazinoisoquinoline derivative and a levorotated isomer of Praziquantel patented by Merck Patent G.m.b.H. as anthelmintics agent. In rabbits infested with S. japonicum, the therapeutic effect of Praziquantel, (-)-was greater than that of dl-praziquantel as rated by the number of the worms in tissues and by liver damage. Histopathological examination showed that liver egg granulomas in the levo-praziquantel group were fewer in no. and smaller in size and were predominantly composed of Pseudotubercles instead of eosinophilic abscesses. Levo-praziquantel is therapeutically superior to praziquantel, while dextro-praziquantel is almost ineffective.

5-(hydroxymethyl)-2-furaldehyde (5-Hydroxymethyl-2-furancarboxaldehyde, 5‐hydroxymethyl‐2‐furfural) is found in garden onion. It is obtainable from various carbohydrates. 5-Hydroxymethyl-2-furancarboxaldehyde is present in tomatoes, tobacco oil etc. It is a constituent of numerous plant species. 5-Hydroxymethyl-2-furancarboxaldehyde is used as an index of heat treatment and deterioration in food such as tomato paste, honey and fruit juices. Also an indicator of adulteration with acid-converted invert sugars. The heterocyclic aldehyde 5‐hydroxymethyl‐2‐furfural (5HMF, Aes‐103, BAX 555) interacts allosterically with the abnormal form of haemoglobin (Hb), HbS, in red blood cells (RBCs) from patients with sickle cell disease (SCD), thereby increasing oxygen affinity and decreasing HbS polymerization and RBC sickling during hypoxia. 5HMF markedly reduced the deoxygenation-induced dehydration of RBCs whether in response to maintained deoxygenation or to cyclical deoxygenation/re-oxygenation. 5HMF was found to inhibit Psickle, an effect which correlated with its effects on sickling. Deoxygenation-induced activation of the Gardos channel and exposure of phosphatidylserine were also inhibited, probably indirectly via reduced entry of Ca(2+) through the Psickle pathway. Effects of 5HMF on KCC were more modest with a slight inhibition in N-ethylmaleimide (NEM, 1 mm)-treated RBCs and stimulation in RBCs untreated with NEM. These findings support the hypothesis that 5HMF may also be beneficial through effects on RBC ion and water homeostasis. AesRx is developing Aes-103 as an orally bioavailable, chronic therapy for SCD. Aes‐103 is currently in phase II clinical trials in SCD patients in the USA and UK. Aes-103 has received orphan designation from the US Food and Drug Administration and is eligible for orphan status in Europe.

Inspyr Therapeutics (formerly GenSpera) developed mipsagargin (previously known as G-202), as a novel thapsigargin-based targeted prodrug that is activated by prostate-specific membrane antigen (PSMA)-mediated cleavage of an inert masking peptide. The active moiety is an inhibitor of the sarcoplasmic/endoplasmic reticulum calcium adenosine triphosphatase (SERCA) pump protein that is necessary for cellular viability. Mipsagargin was granted Orphan Drug designation by the U.S. Food and Drug Administration (FDA) in 2013 for evaluation in patients with hepatocellular carcinoma. In addition, mipsagargin has been studied in phase 2 clinical trial in patients with recurrent or progressive glioblastoma, in patients with clear cell renal cell carcinoma that expresses PSMA. Mipsagargin is expected to be launched on the market in the coming years.

p53 is a critical tumor suppressor and is the most frequently inactivated gene in human cancer. Inhibition of the interaction of p53 with its negative regulator MDM2 represents a promising clinical strategy to treat p53 wild-type tumors. AMG 232 is a potential best-in-class inhibitor of the MDM2-p53 interaction and is currently in clinical trials. Based on X-ray cocrystal structures a model of AMG 232 bound to MDM2 was developed. The model shows that the m-chlorophenyl, the p-chlorophenyl, and C-linked isopropyl fragments of AMG 232 bind to the Leu 26(p53), Trp 23(p53), and Phe 19(p53) pockets of MDM2, respectively. The carboxylic acid forms a salt bridge with His 96 and the isopropyl sulfone forms a novel interaction with the glycine shelf region of MDM2. AMG 232 in phase II in combination with trametinib and dabrafenib in subjects with metastatic melanoma; in phase I for the treatment of solid tumors, multiple myeloma and Acute Myeloid Leukemia.