Rimiducid (AP1903) is a lipid-permeable tacrolimus analogue with homodimerizing activity. Rimiducid homodimerizes an analogue of human protein FKBP12 (Fv) which contains a single acid substitution (Phe36Val). This agent is used to homodimerize the Fv-containing drug-binding domains of genetically engineered proteins such as the iCD40 receptor, Fas intracellular domain or iCaspase 9 resulting in downstream signaling activation during cell therapy. Orphan designation was granted for rimiducid (AP1903) for the treatment of graft-versus-host disease.

D-aspartic acid is an essential amino acid and a key ingredient in various testosterone boosting anti-estrogen supplements. D-aspartic acid is not used to build proteins; instead, it plays a role in making and releasing hormones in the body. It is an endogenous NMDA receptor agonist with similar activity to the L-isomer. D-aspartic acid also enhances the release of luteinizing hormone (LH) and testosterone. This action is mediated in the pituitary by cGMP and in the testis by cAMP, which acts as the second messengers in the signal transduction in the pituitary and testes respectively. The pituitary and testis possess a D-Aspartate racemase, which provides the necessary production of this isomer.

Pfizer was developing PF-04991532, a potent and selective hepatoselective glucokinase activator. PF-04991532 ameliorates hyperglycemia without causing hepatic steatosis in diabetic rats. F-04991532 reduced plasma glucose concentrations independent of changes in insulin concentrations in a dose-dependent manner both acutely and after 28 days of sub-chronic treatment. PF-04991532 may offer glycemic control without inducing hepatic steatosis supporting the evaluation of tissue specific activators in clinical trials. In 2012, Pfizer discontinued the development of the compound.

Puerarin (7, 4’-dihydroxyisolavone-8-β-glucopyranoside) is an active isoflavone extracted from the roots of Pueraria lobata (Willd.) Ohwi. Puerarin is widely used in traditional Chinese medicine, and is clinically used in China for the treatment of coronary artery disease, heart failure, hypertension and myocardial infarction. It has been reported that puerarin had therapeutic effects on diabetes mellitus, arteriosclerosis and myocardial ischemia in animals. Puerarin demonstrated beta-adrenergic receptor blocking effect. On the other hand, puerarin stimulated alpha1-adrenoreceptor to increase glucose uptake into cultured C2C12 cells of mice. Puerarin has been investigated for the treatment (phase II clinical trials) of Alcohol Abuse, Rheumatoid Arthritis and Hypertension.

Dihydromyricetin is a flavonoid component from the Ampelopsis species japonica, megalophylla, and grossedentata; Cercidiphyllum japonicum; Hovenia dulcis; Rhododendron cinnabarinum; some Pinus species; and some Cedrus species, as well as Salix sachalinensis. Dihydromyricetin exerts a more rapid antidepressant-like effect than does a typical antidepressant, in association with enhancement of BDNF expression and inhibition of neuroinflammation. Dihydromyricetin inhibited the proliferative potential of fibroblasts in the lung cancer cells through targeting the activation of Erk1/2 and Akt. Therefore, there is scope for dihydromyricetin to be evaluated further for the treatment of lung cancer. Dihydromyricetin supplementation improves glucose and lipid metabolism as well as various biochemical parameters in patients with nonalcoholic fatty liver disease, and the therapeutic effects of dihydromyricetin are likely attributable to improved insulin resistance and decreases in the serum levels of tumor necrosis factor-alpha, cytokeratin-18, and fibroblast growth factor 21.

Tirasemtiv is a fast skeletal troponin activator and is a candidate amyotrophic lateral sclerosis (AML) therapeutic. It is a small molecule that enhances the signals between motor neurons and neuromuscular junctions. Tirasemtiv increases muscle strength by amplifying the response of muscle when neuromuscular input is diminished secondary to a neuromuscular disease. Tirasemtiv selectively binds to the fast skeletal troponin complex, thus slowing down the rate of calcium release from troponin C and sensitizing muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards as does the force-frequency relationship of a nerve-muscle pair.

SRT2104, also known as GSK2245840, is a novel, first in class, highly selective small molecule activator of the NAD + dependent deacetylase SIRT1. SIRT1 has been suggested as putative therapeutic target in multiple age-related diseases including type 2 diabetes and dyslipidemias. SRT2104 in the phase II of clinical trial to treat type 2 diabetes mellitus and psoriasis also in the phase I for its use in case of colitis. Also was reported, that we report that SRT2104, penetrated the blood-brain barrier, attenuated brain atrophy, improved motor function, and extended survival in a mouse model of Huntington's disease.

Galactitol (dulcitol) is a sugar alcohol, the reduction product of galactose. Galactitol is known to be the major toxic metabolites of galactose. Deficiency of any one of three possible enzymes involved in the metabolism of galactose: galactokinase, transferase or epimerase results in galactosemia. Any single deficient enzyme can result in cataract through the accumulation of galactitol in the lens. Accumulation of galactose and galactitol within the lens cells leads to an increase in intracellular osmotic pressure and an influx of fluid in the lens. Kinoshita was the first to demonstrate the hyperosmotic effects of intracellular sorbitol or galactitol accumulation and to postulate that the resulting cellular swelling can lead to increased membrane permeability and a series of complex biochemical changes associated with sugar cataract formation. The excretion of abnormal quantities of galactitol in the urine of galactosemia patients is characteristic of this disorder. A patent claims galactitol as carrier for the therapeutic agent since galactitol enhances the chemical and physical stability of the drug and allows faster reconstitution of the formulation in water than mannitol.