Calcium lactate is the salt that consists of two lactate anions for each calcium cation (Ca2+); this salt is used as a calcium supplement to treat hypocalcemia. However, as a source of free calcium, this salt is less convenient than calcium citrate. Calcium lactate inhalation powder also called as PUR118 participated in phase I clinical trials to determine whether this formulation was safe and tolerable in a population of subjects with Cystic Fibrosis (CF). PUR118 also was used in another clinical trials to evaluate its effect on ozone-induced airway Inflammation in healthy normal volunteers in case of Chronic Obstructive Pulmonary Disease (COPD). The obtained results revealed that PUR118 reduced the severity of acute exacerbations in COPD and CF and had the beneficial impacts on mortality, morbidity, and quality of life in affected individuals. However, both studies were discontinued.

Glycine (Cly) is a natural amino acid neurotransmitter that acts as a co-agonist at Glutamate [NMDA] receptors in the brain and is an activator of glycine receptors, GLRA1-3, GLRB. The abnormal Gly levels have been implicated in neuropsychiatric disorders. Alterations in Gly levels are implicated in several diseases of the central nervous system. Glycine was studied in phase II of clinical trials in patients with schizophrenia. The results have shown that using of glycine was associated with reduced symptoms with promising effect sizes and a possibility of improvement in cognitive function. Besides, glycine was also studied in clinical trials phase II in children with cystic fibrosis. The clinical, spirometric and inflammatory status of subjects with cystic fibrosis improved after just 8 weeks of glycine intake, suggesting that this amino acid might constitute a novel therapeutic tool for these patients. In addition, Gly was proposed as a biomarker for brain tumor malignancy. Glycine is a component of a nutrients mixture for peripheral administration to well-nourished mildly catabolic adult patients who require only short-term parenteral nutrition.

Seliciclib (CYC202, R-roscovitine) is a second-generation orally available cyclin-dependent kinases (CDKs) inhibitor that competes for ATP binding sites on these kinases. It is a direct inhibitor of cyclin CDK2/E, CDK2/A and it has inhibitory effects on cyclin H/CDK7, CDK5, and CDK9. CDKs are enzymes that are central to the process of cell division and cell cycle control and play pivotal roles in cancer cell growth and DNA damage repair. Seliciclib exerts an anti-proliferative effect via several key mechanisms: selective downregulation of proliferative and survival proteins and upregulation of p53, leading to growth arrest or apoptosis. The second one is decreasing phosphorylation of Rb and modulating E2F transcriptional activity leading to growth arrest or apoptosis. Seliciclib is currently in phase II clinical trial as a drug candidate for the treatment of Cushing's disease and as a potential therapeutic agent for the treatment of cystic fibrosis (CF). In addition, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Amelubant, its metabolite BIIL 260 (formed by removal of the ethoxycarbonyl protecting group), and its major metabolite BIIL 315 (formed by removal of the protecting group and glucuronidation) had potent in vitro and in vivo Leukotriene B4 receptor antagonistic properties. Amelubant has been in phase II clinical trials by Boehringer Ingelheim for the treatment of cystic fibrosis, chronic obstructive pulmonay disease, bronchial asthma and rheumatoid arthritis. However, this research has been discontinued. In 2002, orphan drug designation was received in E.U. for the treatment of cystic fibrosis. Serious adverse events of Amelubant were characterized by increased presentation of respiratory signs and/or symptoms associated with pulmonary exacerbation and resulted in admission to a hospital and/or administration of IV antibiotics.

N6022 is a novel, first-in-class drug with potent reversible inhibitory activity against S-nitrosoglutathione reductase (GSNOR) and a potential agent for the treatment of acute asthma and cystic fibrosis (CF). Decreased levels of GSNO in the lungs of asthmatics and cystic fibrosis patients have been attributed to increased GSNO catabolism via GSNO reductase (GSNOR) leading to loss of GSNO- and NO- mediated bronchodilatory and anti-inflammatory actions. N6022 restore GSNO levels by inhibiting GSNOR. Inhibition of GSNOR by N6022 has shown safety and efficacy in animal models of asthma, chronic obstructive pulmonary disease, and inflammatory bowel disease. N6022 reduced bronchoconstriction and pulmonary inflammation in a mouse model of asthma. The significant bronchodilatory and anti-inflammatory actions of N6022 in the airways are consistent with restoration of GSNO levels through GSNOR inhibition.

Avelestat, also known as AZD9668, is a novel, oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms, and disease progression in NE-driven respiratory diseases such as bronchiectasis, Cystic Fibrosis and chronic obstructive pulmonary disease via its role in the inflammatory process, mucus overproduction, and lung tissue damage. Its development was discontinued due to unknown reasons. Nevertheless, this drug in the phase II of clinical trial as adjunctive therapy in improving insulin sensitivity of insulin-resistant type 2 diabetic subjects. The drug's clinical profile suggests that it will be well tolerated with few, if any, side effects, and the existence of simple methods that can indirectly measure its activity in vivo.

DMP-777 (also termed L-694458) a cell permeant b-lactam inhibitor of a human leukocyte elastase was developed for treatment cystic fibrosis, juvenile rheumatoid arthritis.

Benzamil is a derivative of amiloride, a potassium sparing diuretic, and is an inhibitor of Na /H and Na /Ca channels. Amiloride works by directly blocking the epithelial sodium channel (ENaC) thereby inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys (this mechanism is the same for triamterene). This promotes the loss of sodium and water from the body, but without depleting potassium. Benzamil has being shown to attenuate the development of hypertension in Dahl salt-sensitive rats. Benzamil has been studied as a possible treatment for cystic fibrosis. Benzamil was suggested to be a useful sodium channel blocker for the long-term treatment of the biochemical defect in the lungs of patients with cystic fibrosis.

Ferric picolinate and ferric acetohydroxamate are effective anti-biofilm compounds against both lab and clinical strains of P. aeruginosa and are readily nebulized into particles of suitable size for lung delivery.

Auraptene (7-Geranyloxycoumarin) is the best known and most abundant prenyloxycoumarin present in nature. It is synthesized by various plant species, mainly those of the Rutaceae and Umbelliferae (Apiaceae) families, comprising many edible fruits and vegetables such as lemons, grapefruit, and orange. Auraptene has shown a remarkable effect in the prevention of degenerative diseases, in particular, it has been reported to be one the most promising known natural chemopreventive agents against several types of cancer. The effect in humans is not yet known.