SN38 (7-ethyl-10-hydroxy camptothecin) is a prominent and efficacious anticancer agent. It is poorly soluble in both water and pharmaceutically approved solvents; therefore, the direct formulation of SN38 in solution form is limited. SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1. Currently, the water soluble prodrug of SN38, irinotecan (CPT-11), is formulated as a low pH solution and is approved for chemotherapy. SN38 causes the strongest inhibition of DNA topoisomerase I, followed by CPT and then CPT-11. CPT-11 dose dependently shifts the position of relaxed DNA in the direction of nicked DNA, but SN38 and CPT shows no effect on the position of relaxed DNA. SN38 dose-dependently and time-dependently inhibit DNA synthesis. Respective IC50 values of SN38, in DNA synthesis is 0.077 uM.

Elacridar is an oral bioenhancer that targets multiple drug resistance in tumors. Elacridar is a strong and relatively specific inhibitor of P-gp and BCRP, two main efflux transporters. Development of elacridar is assumed to have been discontinued.

JNJ-38877605 is an orally available, small molecule inhibitor of the proto-oncogene c-Met (hepatocyte growth factor receptor [HGFR]) with potential antineoplastic activity. c-Met inhibitor JNJ-38877605 selectively binds to c-Met, thereby inhibiting c-Met phosphorylation and disrupting c-Met signal transduction pathways. JNJ-38877605 was in Phase I clinical trials. Combined clinical and correlative preclinical studies suggest that renal toxicity of JNJ-38877605 is caused by the formation of species-specific insoluble metabolites. These observations preclude further clinical development of JNJ-38877605.

Isopropyl β-D-1-thiogalactopyranoside (IPTG) is a molecular biology reagent that induces β-galactosidase activity in many bacteria. This compound is a molecular mimic of allolactose, a lactose metabolite that triggers transcription of the lac operon, and it is therefore used to induce protein expression where the gene is under the control of the lac operator. Like allolactose, IPTG binds to the lac repressor and releases the tetrameric repressor from the lac operator in an allosteric manner, thereby allowing the transcription of genes in the lac operon, such as the gene coding for beta-galactosidase, a hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides. But unlike allolactose, the sulfur atom creates a chemical bond which is non-hydrolyzable by the cell, preventing the cell from metabolizing or degrading the inducer.

AMG-151 [AMG 151, ARRY-403] was under development with Amgen for the treatment of type 2 diabetes mellitus (T2DM). AMG 151 binds to glucose-bound glucokinase distinctly from glucose- or adenosine triphosphate–binding sites to activate glucokinase selectively. AMG 151 was in a phase I trial for the treatment of Type 2 diabetes. AMG 151 in a twice-daily dosing regimen decreased fasting and postprandial glucose in patients with type 2 diabetes inadequately controlled with metformin. In all AMG 151 once-daily dose groups and in the AMG 151 200-mg twice-daily dose group, significant reductions were observed in glucose AUC0–240 in after a MTT from baseline to day 28 compared with placebo. However, Amgen disconinued the development of AMG-151.