LABRADIMIL, a synthetic bradykinin analog, is a potent bradykinin B2 receptor agonist. It increases vascular permeability by the activation of B2 receptors on the vascular endothelium. It also selectively increases uptake of molecular tracers in brain tumors.

HM-30181 is a highly selective and potent inhibitor of Multi-drug resistance 1 (MDR1, ABCB1), also known as P-glycoprotein (P-gp). Co-administration of HM30181 greatly increased oral bioavailability of tubulin-stabilizing chemotherapeutic agent paclitaxel. Oraxol is an oral dosage form of paclitaxel administered orally with the HM30181A molecule. Oraxol offers patients with paclitaxel-responsive tumors the possibility of oral therapy without the requirement for premedication to prevent infusion-related hypersensitivity-type reactions. Current clinical data suggests the promising potential of a better clinical response and tolerability profile, which can likely to be attributed to the better pharmacokinetic profile achieved. Oraxol is presently in a Phase 3 trial in metastatic breast cancer and poised to enter into a combination study for treatment of advanced gastric cancer with ramucirumab through a clinical trial collaboration with Eli Lilly and Company.

Caricotamide is a synthetic co-substrate that activates the human endogenous enzyme NRH:quinone oxidoreductase 2 (NQO2) with potential chemoadjuvant activity. When caricotamide is administered simultaneously with the prodrug tretazicar, NQO2 converts tretazicar to the bifunctional alkylating agent dinitrobenzamide, which is capable of forming a high degree of DNAinterstrand cross-links, resulting in the inhibition of DNA replication and the induction of apoptosis. NQO2 has been found to be over-expressed in cancers such as hepatocellular carcinoma (HCC), colorectal and ovarian cancers.

Salclobuzate sodium was developed as an oral absorption promoter. This compound had to “chaperone” poorly permeable payloads across the intestine. Information about the current use of this compound is not available.

Salcaprozate sodium (SNAC), an oral absorption promoter that was discovered as part of a screen to identify carrier-based permeation enhancers (Pes) that could “chaperone” poorly permeable payloads across the intestine. Its potential therapeutic application as a delivery agent was tested in many formats: taste-masked liquids, tablets, and soft gelatin capsules. SNAC is the most extensively tested carrier and the only PE approved in an oral formulation designed to improve oral bioavailabilities. The mechanism of action of this compound is not clear. However, Novo Nordisk offered a mechanism of action for SNAC in its non-enteric coated tablet of the glucagon-like peptide 1 analog, semaglutide. SNAC formed a complex around the semaglutide in the stomach and caused a transient increase in local pH around the molecule. It is claimed that semaglutide is protected against pepsin by SNAC and that solubility was increased, resulting in an increased concentration-dependent flux of semaglutide across the gastric mucosa, using a transcellular mechanism as the tablet comes in intimate contact with the epithelium. Clinical trials for patients with Type 2 Diabetes have shown that the oral semaglutide co-formulated with 300 mg SNAC could be used for further clinical development.

LAUROCAPRAM is a percutaneous permeation enhancer facilitating absorption of different chemicals upon their application to the skin. Its enhancing effect is associated with different mechanisms: incorporation of its dodecyl group into the lipid bilayer, an increase of the motion of the alkylic chains of lipids, and lipid fluidization.

Cridanimod (Virexxa) is a small-molecule immunomodulator and interferon inducer, which, in preliminary studies, has been shown to increase progesterone receptor expression in endometrial tissue. Restoration of progesterone receptor expression may re-sensitize endometrial tumor tissue to progestin therapy in previously unresponsive tumors. Cridanimod was originally developed by Polysan and Pharmsynthez and licensed to Xenetic Biosciences. Virexxa is currently being studied in an ongoing Phase 2 multi-national study in conjunction with progestin therapy for the treatment of endometrial cancer in women with the recurrent or persistent disease who have failed progestin monotherapy.

Salclobuzate sodium was developed as an oral absorption promoter. This compound had to “chaperone” poorly permeable payloads across the intestine. Information about the current use of this compound is not available.