Setmelanotide (IMCIVREE™) is a melanocortin-4 (MC4) receptor agonist developed by Rhythm Pharmaceuticals (Rhythm) for the treatment of ultrarare genetic disorders of obesity. Setmelanotide was approved on 27 November 2020 in the USA as a subcutaneous (SC) injectable formulation for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency confirmed by genetic testing demonstrating variants in POMC, PCSK1, or LEPR genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). Rhythm are also developing the drug for the treatment of obesity associated with other rare genetic disorders including Bardet–Biedl Syndrome, Alström Syndrome, POMC and other MC4R pathway heterozygous defciency obesities, and POMC epigenetic disorders.

NEO 212 is novel DNA alkylating agent exhibiting superior activity against breast cancer cells in vitro and intracranial triple-negative tumor growth in vivo. NEO212 is a conjugate of temozolomide (TMZ,) with the natural product perillyl alcohol (POH). NEO 212 causes DNA damage and cell death much more efficiently than TMZ because linkage with POH increased it's biological half-life and thus provided greater opportunity for placement of cytotoxic DNA lesions.

Sodium lactate is primarily indicated as a source of bicarbonate for prevention or control of mild to moderate metabolic acidosis in patients with restricted oral intake whose oxidative processes are not seriously impaired. Sodium Lactate is most commonly associated with an E number of “E325” Sodium Lactate blends are commonly used in meat and poultry products to extend shelf life and increase food safety. They have a broad antimicrobial action and are effective at inhibiting most spoilage and pathogenic bacteria. In addition sodium lactate is used in cosmetics as a humectant, providing moisture.

Alcohols exhibit rapid broad-spectrum antimicrobial activity against vegetative bacteria (including mycobacteria), viruses, and fungi but are not sporicidal. They are, however, known to inhibit sporulation and spore germination, but this effect is reversible. Because of the lack of sporicidal activity, alcohols are not recommended for sterilization but are widely used for both hard-surface disinfection and skin antisepsis. Lower concentrations may also be used as preservatives and to potentiate the activity of other biocides. Many alcohol products include low levels of other biocides (in particular chlorhexidine), which remain on the skin following evaporation of the alcohol, or excipients (including emollients), which decrease the evaporation time of the alcohol and can significantly increase product efficacy. Ethanol in combination with: chlorhexidine gluconate 1% was approved to use in surgical hand antiseptic. It significantly reduces the number of microorganisms on the hands and forearms prior to surgery or patient care. Ethanol is also used as a co-solvent to dissolve many insoluble drugs and to serve as a mild sedative in some medicinal formulations. Ethanol is metabolized by the hepatic enzyme alcohol dehydrogenase. Ethanol affects the brain’s neurons in several ways. It alters their membranes as well as their ion channels, enzymes, and receptors. Alcohol also binds directly to the receptors for acetylcholine, serotonin, GABA, and the NMDA receptors for glutamate. The sedative effects of ethanol are mediated through binding to GABA receptors and glycine receptors (alpha 1 and alpha 2 subunits). It also inhibits NMDA receptor functioning. In its role as an anti-infective, ethanol acts as an osmolyte or dehydrating agent that disrupts the osmotic balance across cell membranes.

CG-200745 is a novel inhibitor of histone deacetylases (HDACs), initially developed by CrystalGenomics, Inc for treatment of various hematological and solid cancers. Combinations of CG-200745 with SN38 (the active form of irinotecan), or oxaliplatin were more effective than the agents alone when used to inhibit the growth of HCT116 cells. The protein expressions of acetyl-H3, p21, caspase-3, -8, and -9, PARP, and XIAP were affected in a time- and dose-dependent manner in HCT116 cells treated with the CG-200745 alone or combined CG-200745 and SN-38. In HCT116 xenografts, the HDACI CG-200745 in combination with irinotecan dramatically inhibited tumor growth without showing additive toxicity.

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.

Amuvatinib (formerly known as MP470) is an oral multi-targeted tyrosine kinase inhibitor, which play critical roles in transducing growth signals to cancer cells. It suppresses c-MET, c-RET and the mutant forms of cKIT, PDGFR and FLT3. It also disrupts DNA repair likely through suppression of homologous recombination protein Rad51, an important survival pathway in many human cancers. In vitro and in vivo data have demonstrated amuvatinib synergy with DNA damaging agents including etoposide and doxorubicin. Overall, in the amuvatinib clinical development program, over 200 subjects were exposed to at least one dose of amuvatinib. In the Phase 1b clinical study in combination with carboplatin and etoposide, responses in small cell lung cancer (SCLC), neuroendocrine as well as other tumor types were observed. Human pharmacokinetic data suggest that co-administration of amuvatinib did not alter exposures of standard of care agents including carboplatin, etoposide, doxorubicin, paclitaxel, topotecan or erlotinib as measured by overall exposure. In the first-in-human study, durable clinical benefit was observed in the gastrointestinal stromal tumors (GIST) with modulation of Rad51 observed in skin punch biopsies. In clinical trials, amuvatinib has demonstrated a wide therapeutic window and shows minimal toxicity in the expected therapeutic dose range, despite suppressing several signaling pathways within cells. However, in spite of this, this drug was discontinued, because it was not pre-specified primary endpoints in the clinical proof of concept (cPOC) stage. But the combination of MP470 and Erlotinib, which target the HER family/PI3K/Akt pathway may represent a novel therapeutic strategy for prostate cancer.