Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. Enzastaurin (LY317615) is a potent PKCβ selective inhibitor. Enzastaurin suppresses angiogenesis and was advanced for clinical development based upon this antiangiogenic activity. Enzastaurin suppresses tumor growth through multiple mechanisms: direct suppression of tumor cell proliferation and the induction of tumor cell death coupled to the indirect effect of suppressing tumor-induced angiogenesis. Enzastaurin is an orally administered drug that was intended for the treatment of solid and haematological cancers. Enzastaurin had shown encouraging preclinical results for the prevention of angiogenesis, inhibition of proliferation and induction of apoptosis as well as showing limited cytotoxicity within phase I clinical trials. However, during its assessment in phase II and III clinical trials the efficacy of enzastaurin was poor both in combination with other drugs and as a single agent. Eli Lilly discontinued development of enzastaurin after top-line data from the double-blind, international Phase III PRELUDE trial in 758 DLBCL patients showed that enzastaurin missed the primary endpoint of improving DFS vs. placebo.

Etiocholanone is an androstane neurosteroid. Etiocholanone potentiates GABA-A receptor currents and exerts anticolvunsant properties in rodents. Etiocholanolone demostrates pyrogenic properties.

Pregnanediol is a chief steroid metabolite of progesterone that is biologically inactive and occurs as pregnanediol glucuronate in the urine. Pregnanediol has two hydroxyl groups, at 3-alpha and 20-alpha. A test can be done to measure the amount of pregnanediol in urine. The urine test offers an indirect way to measure progesterone levels in the body. It is a standard in the colorimetric determination of urinary pregnanediol in clinical laboratories.

Halofuginone is a low molecular weight quinazolinone alkaloid, and a potent inhibitor of collagen alpha1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also effectively suppresses tumor progression and metastasis in mice. Halofuginone is a potent inhibitor of collagen a1(I) and matrix metalloproteinase 2 (MMP-2) gene expression. Halofuginone also suppresses extracellular matrix deposition and cell proliferation. Also was shown that halofuginone increased apoptosis in α smooth muscle actin- and prolyl 4-hydroxylase β-expressing cells in mdx diaphragm and in myofibroblasts, the major source of extracellular matrix. The profound antitumoral effect of halofuginone is attributed to its combined inhibition of tumour-stromal support, vascularization, invasiveness, and cell proliferation. HT-100 (delayed-release halofuginone), currently in clinical phase 1b/2a in five U.S. hospitals, is a small molecule drug candidate taken orally for the treatment of Duchenne muscular dystrophy (DMD) patients primarily through its ability to reduce fibrosis and inflammation and promote muscle fiber regeneration. The medicine candidate has been granted orphan drug designation in the U.S. and the EU — meaning it has been commercially undeveloped due to its limited profitability — and fast-track designation in the U.S. — an FDA process that aims to facilitate the development and patients’ reach to novel therapies for unmet medical needs.

Tributyrin is a prodrug of natural butyrate. It is a neutral short-chain fatty acid triglyceride that is likely to overcome the pharmacokinetic drawbacks of natural butyrate as a drug. Tributyrin has potent antiproliferative, proapoptotic and differentiation-inducing effects in neoplastic cells. Compared with butyrate, tributyrin has more favorable pharmacokinetics and is well tolerated. Because it is rapidly absorbed and chemically stable in plasma, tributyrin diffuses through biological membranes and is metabolized by intracellular lipases, releasing therapeutically effective butyrate over time directly into the cell. Tributyrin may, at least in part, exert its growth-reducing and differentiation-inducing effect in Caco-2 cells by an upregulation of the vitamin D receptor; this may provide a useful therapeutic approach in chemoprevention and treatment of colorectal cancer. In phase I study of the orally administered tributyrin there was no consistent increase in hemoglobin F. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose. Development of tributyrin as an anticancer agent was discontinued.

Bentiamine (also known as dibenzoyl thiamine), a derivative of thiamine, is rapidly absorbed and converted to thiamine. Experiments on rodent have shown that this compound had low toxicity and absence of carcinogenicity.

Corticosterone is an adrenocortical steroid, the major glucocorticoid that has modest but significant activities as a mineralocorticoid and a glucocorticoid. Corticosterone is of minor importance in humans but is known, that it has a profound effect on the structure and function of the hippocampus. Brain corticosterone may involve memory storage and emotional stress might cause increases in plasma corticosterone.

Androsterone, a neurosteroid, acts as a positive allosteric modulator of GABA(A) receptors, that can cross into the brain and could have effects on brain function. It was discovered, that the association of beta subunits with alpha subunits GABA(A) receptor affects the sensitivity of glycine receptors to androsterone. In spite of that, androsteron is considered as an inactive metabolite of testosterone. In addition, was studied that androsterone possessed anticonvulsant properties. Although of low potency, the androsterone was present in high abundance and was able to represent endogenous modulator of seizure susceptibility.

11-Deoxycortisol (also known as cortodoxone) is the predominant deoxycorticosteroid and is the immediate precursor of cortisol, which is formed by the enzymatic action of 11beta-hydrozylase (P450). Deficiency of this enzyme causes congenital adrenal hyperplasia, which is characterized by hypertension. 11-deoxycortisol is measured as part of the Metyrapone Test. Metyrapone blocks the formation of cortisol, resulting in increased secretion of Adrenocorticotropic hormone (ACTH) and 11-deoxycortisol in normal individuals.