Seviteronel (VT-464) is a 17,20-lyase selective inhibitor of CYP17A1, which plays key roles in adrenal and intratumoral de novo biosynthesis of androgens. The inhibition of 17,20-lyase activity by seviteronel (VT-464) is enough to reduce androgen levels, and its preserving of 17alpha-hydroxylase activity largely avoids interference with the production of other steroidal hormones. Seviteronel (VT-464) also has shown AR-antagonist activity independent of CYP17 enzyme inhibition. It is currently in phase 2 clinical trials as a therapeutic for castration-resistant prostate cancer patients.

BI-224436 is an HIV-1 integrase inhibitor with effective antiviral activity that acts through a mechanism that is distinct from that of integrase strand transfer inhibitors (INSTIs). This 3-quinolineacetic acid derivative series was identified using an enzymatic integrase long terminal repeat (LTR) DNA 3'-processing assay. A combination of medicinal chemistry, parallel synthesis, and structure-guided drug design led to the identification of BI 224436 as a candidate for preclinical profiling. It has antiviral 50% effective concentrations (EC50s) of <15 nM against different HIV-1 laboratory strains and cellular cytotoxicity of >90 μM. BI-224436 also retains full antiviral activity against recombinant viruses encoding INSTI resistance substitutions N155S, Q148H, and E92Q. In drug combination studies performed in cellular antiviral assays, BI-224436 displays an additive effect in combination with most approved antiretrovirals, including INSTIs. BI-224436 has drug-like in vitro absorption, distribution, metabolism, and excretion (ADME) properties, including Caco-2 cell permeability, solubility, and low cytochrome P450 inhibition. It exhibited excellent pharmacokinetic profiles in rat (clearance as a percentage of hepatic flow [CL], 0.7%; bioavailability [F], 54%), monkey (CL, 23%; F, 82%), and dog (CL, 8%; F, 81%). Based on the excellent biological and pharmacokinetic profile, BI 224436 was advanced into phase 1 clinical trials. Trials with clinical candidate BI-224436 were put on hold despite promising results.

(R)-Ibuprofen, a nonsteroidal anti-inflammatory, is the less active enantiomer of ibuprofen. (S)-enantiomer of ibuprofen has the desired therapeutic effect (160 times more active than its (R)-enantiomer) in the in vitro inhibition of prostaglandin synthesis, while the (R)- ibuprofen is inactive. The accumulation of (R)- ibuprofen can cause serious side effects to the human body such as gastrointestinal pain and production of “hybrid” triglycerides between (R)- ibuprofen and Coenzyme A, which disrupt normal lipid metabolism and membrane function. The R(-)-isomer is almost inactive in inhibiting COX-2.

Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees. Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae), also known as “kalmegh” in India, is a widely distributed plant in Asia. In many traditional formulations, the aerial parts have been used as anti-inflammatory and antipyretic drugs for the treatment of a variety of chronic and infectious diseases. Neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.

20-Hydroxyecdysone is a naturally occurring ecdysteroid hormone, which is marketed as dietary supplements that can increase strength and muscle mass during resistance training, particularly bodybuilding. It was found, that 20-hydroxyecdysone did not affect body composition or training adaptations nor did they influence the anabolic/catabolic hormone status or general markers of catabolism in resistance-trained males. Because is known, that ecdysteroids have been shown to prevent various changes in mammalian tissues after female sex hormone deprivation. 20-Hydroxyecdysone also was investigated on these properties. It was found in rats, that 20-Hydroxyecdysone had a beneficial effect on reducing blood pressure and consequently preventing dilated cardiac hypertrophy. Some in vitro experiments showed, that 20-hydroxyecdysone had effects on lymphocytes and neutrophils, and may act as an immunomodulator.

CMX-2043 is a is an α-lipoic acid analog developed by Ischemix LLC for reduction of cellular injury and organ damage due to ischemia-reperfusion injury (IRI). CMX-2043 was more effective than lipoic acid in antioxidant effect, activation of insulin receptor kinase, soluble tyrosine kinase, and Akt phosphorylation, and activated insulin-like growth factor 1 as effectively as lipoic acid. In a rat model of cardiac ischemia-reperfusion injury, treatment with CMX-2043 reduced myocardial IRI as measured by the myocardial infarction/area at risk ratio, and reduced the incidence of arrhythmia. In a 360-patient Phase 2 trial, CMX-2043 demonstrated safety but did not meet pre-specified endpoints regarding prevention of contrast-induced acute kidney injury or cardiac injury in cardiac catheterization lab subjects, and no further development of the drug was reported.

Cyproconazole is an azole fungicide, introduced to the market by Sandoz (now Syngenta). It is used to control a wide range of fungi on cereal crops, coffee, sugar beet, fruit trees, grapes, including rust on cereal crops, powdery mildew on cereal crops, fruit tree and grapes, and scab on apple. The cyproconazole structure exists in four stereoisomeric forms as two diastereoisomeric pairs of enantiomers. Cyproconazole is a 1:1 mixture of the two diastereomeric pairs, each of which is a 1:1 mixture of the enantiomers (i.e., all four stereoisomers are present in similar amounts). Cyproconazole inhibits the fungal enzyme eburicol 14-alpha-demethylase, which is involved in the biosynthesis of sterol, a component of a fungal cell wall.