Lorlatinib is an investigational medicine that inhibits the anaplastic lymphoma kinase (ALK) and ROS1 proto-oncogene. Lorlatinib was specifically designed to inhibit tumor mutations that drive resistance to other ALK inhibitors. Lorlatinib has in vitro activity against ALK and number of other tyrosine kinase receptor related targets including ROS1, TYK1, FER, FPS, TRKA, TRKB, TRKC, FAK, FAK2, and ACK. Lorlatinib demonstrated in vitro activity against multiple mutant forms of the ALK enzyme, including some mutations detected in tumors at the time of disease progression on crizotinib and other ALK inhibitors. Moreover, lorlatinib possesses the capability to cross the blood-brain barrier, allowing it to reach and treat progressive or worsening brain metastases as well. Lorlatinib is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) indicated for the treatment of patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on a) the prior use of crizotinib and at least one other ALK inhibitor for metastatic disease, or b) the prior use of alectinib as the first ALK inhibitor therapy for metastatic disease, or c) the prior use of certinib as the first ALK inhibitor therapy for metastatic disease.

Glutamine is a non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed. Glutamine is used for nutritional supplementation, also for treating dietary shortage or imbalance.

Sodium phenylbutyrate is a salt of an aromatic fatty acid. The compound is used to treat urea cycle disorders, because its metabolites offer an alternative pathway to the urea cycle to allow excretion of excess nitrogen. Sodium phenylbutyrate is also a histone deacetylase inhibitor and chemical chaperone, leading respectively to research into its use as an anti-cancer agent and in protein misfolding diseases such as cystic fibrosis. It is used as adjunctive therapy for the management of chronic urea cycle disorders due to deficiencies in carbamylphosphate (CPS), ornithine transcarbamylase (OTC), or argininosuccinic acid synthetase. It is indicated in all neonatal- onset efficiency presenting within the first 28 days of life. Also indicated in patients with late-onset, presenting after the first month of life with a history of hyperammonemic encephalopathy. Sodium phenylbutyrate is a pro-drug and is rapidly metabolized to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine. The kidneys then excrete Phenylacetylglutamine. PBA (phenylbutyric acid) is absorbed from the intestine and converted by way of β-oxidation to the active moiety, phenylacetic acid (PAA). PAA is conjugated with glutamine in the liver and kidney by way of N-acyl coenzyme A-l-glutamine N-acyltransferase to form phenylacetylglutamine (PAGN). Like urea, PAGN incorporates two waste nitrogens and is excreted in the urine. On a molar basis, it is comparable to urea (each containing two moles of nitrogen). Therefore, phenylacetylglutamine provides an alternate vehicle for waste nitrogen excretion.

Budesonide is a glucocorticoid used in the management of asthma, the treatment of various skin disorders, allergic rhinitis and ulcerative colitis. The precise mechanism of corticosteroid actions on inflammation in asthma is not well known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory activities against multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic- and non-allergic-mediated inflammation. The anti-inflammatory actions of corticosteroids may contribute to their efficacy in asthma. Commonly reported side effects of budesonide include: acne vulgaris, moon face, and bruise. Other side effects include: ankle edema, hirsutism, weakness, arthralgia, nausea, and rhinitis. Ketoconazole, a potent inhibitor of cytochrome P450 (CYP) isoenzyme 3A4 (CYP3A4), the main metabolic enzyme for corticosteroids, increased plasma levels of orally ingested budesonide.

Phenylacetic acid (abr. PAA and synonyms are: α-toluic acid, benzeneacetic acid, alpha tolylic acid, 2-phenylacetic acid, β-phenylacetic acid) is an organic compound containing a phenyl functional group and acarboxylic acid functional group. Because it is used in the illicit production of phenylacetone (used in the manufacture of substituted amphetamines), it is subject to controls in countries including the United States and China Phenylacetic acid is used in some perfumes, possessing a honey-like odor in low concentrations, and is also used in penicillin G production. It is also employed to treat type II hyperammonemia to help reduce the amounts of ammonia in a patient's bloodstream by forming phenylacetyl-CoA, which then reacts with nitrogen-rich glutamine to form phenylacetylglutamine. This compound is then secreted by the patient's body. In Phase 2 of clinical research it investigated in the treatment of Brain and Central Nervous System Tumors.

Acyclovir is a synthetic antiviral nucleoside analogue. A screening program for antiviral drugs begun at Burroughs Wellcome in the 1960s resulted in the discovery of acyclovir in 1974. Preclinical investigation brought the drug to clinical trials in 1977 and the first form of the drug (topical) was available to physicians in 1982. Activity of acyclovir is greatest against herpes 1 and herpes 2, less against varicella zoster, still less against Epstein-Barr, and very little against cytomegalovirus. Acyclovir is an antiviral agent only after it is phosphorylated in infected cells by a viral-induced thymidine kinase. Acyclovir monophosphate is phosphorylated to diphosphate and triphosphate forms by cellular enzymes in the infected host cell where the drug is concentrated. Acyclovir triphosphate inactivates viral deoxyribonucleic acid polymerase.

Levodopa (L-DOPA) was first isolated from seedlings of Vicia faba by Marcus Guggenheim in 1913. Levodopa, a dopamine precursor, is an effective and well-tolerated dopamine replacement agent used to treat Parkinson's disease. Oral levodopa has been widely used for over 40 years, often in combination with a dopa-decarboxylase inhibitor carbidopa, which reduces many treatment complications, extending its half-life and increasing levodopa availability to the brain. Entacapone, a catechol-O-methyltransferase inhibitor, can also be used to improve the bioavailability of levodopa, especially when used in conjunction with a carbidopa.

Valproic acid (VPA; valproate; di-n-propylacetic acid, DPA; 2-propylpentanoic acid, or 2-propylvaleric acid) was first synthesized in 1882, by Burton. FDA approved valproic acid for the treatment of manic episodes associated with bipolar disorder, for the monotherapy and adjunctive therapy of complex partial seizures and simple and complex absence seizures and adjunctive therapy in patients with multiple seizure types that include absence seizures and for the prophylaxis of migraine headaches. The mechanisms of VPA which seem to be of clinical importance in the treatment of epilepsy include increased gamma-aminobutyric acid (GABA)-ergic activity, reduction in excitatory neurotransmission, and modification of monoamines. Recently, it was discovered that the VPA is a class I selective histone deacetylase inhibitor. This activity can be distinguished from its therapeutically exploited antiepileptic activity.

Folic Acid is a B complex vitamin containing a pteridine moiety linked by a methylene bridge to para-aminobenzoic acid, which is joined by a peptide linkage to glutamic acid. Conjugates of Folic Acid are present in a wide variety of foods, particularly liver, kidneys, yeast and leafy green vegetables. Commercially available Folic Acid is prepared synthetically. Folic Acid occurs as a yellow or yellowish-orange crystalline powder and is very slightly soluble in water and insoluble in alcohol. Aqueous solutions of Folic Acid are heat sensitive and rapidly decompose in the presence of light and/or riboflavin; solutions should be stored in a cool place protected from light. Folic Acid is effective in the treatment of megaloblastic anemias due to a deficiency of Folic Acid (as may be seen in tropical or nontropical sprue) and in anemia of nutritional origin, pregnancy, infancy, or childhood. Folic Acid is relatively nontoxic in man. Rare instances of allergic responses to Folic Acid preparations have been reported and have included erythema, skin rash, itching, general malaise, and respiratory difficulty due to bronchospasm. Endocyte is developing an intravenous (IV) formulation of folic acid, called Neocepri®, which is intended for the diagnosis of positive folate receptor-positive status in patients with ovarian cancer when administered prior to the radioactive medicine, technetium Tc99m Etarfolatide. The benefits of Neocepri® are its ability to reduce the background activity observed on single photon emission computed tomography (SPECT) imaging in most normal, nontarget tissues (e.g. intestines, liver, kidney, spleen), thereby improving the image quality of the scans. The product had been granted orphan drug designation in the EU. Endocyte had filed a conditional marketing authorization application (CMA) with the European Medicines Agency (EMA) for Neocepri®.