The World Health Organization's ATC classification organizes medical drugs based on therapeutic properties, chemical composition, and anatomy. It helps make essential medicines readily available globally and is widely used in the pharmaceutical industry.
Ademetionine is a naturally occurring amino acid present in virtually all body tissues and fluids. Ademetionine functions primarily as a co-enzyme and donor transfer of the methyl group (transmethylation) is an essential metabolic process in humans and animals. Ademetionine is also a precursor in the formation of physiological sulfurated compounds (cysteine, taurine, glutathione, CoA, etc.) via transsulfuration. It is used for the treatment of intrahepatic cholestasis.
Agalsidase alfa catalyses the hydrolysis of Gb3, cleaving a terminal galactose residue from the molecule. Treatment with the enzyme has been shown to reduce accumulation of Gb3 in many cell types including endothelial and parenchymal cells. Agalsidase alfa has been produced in a human cell line to provide for a human glycosylation profile that can influence uptake by mannose-6-phosphate receptors on the surface of target cells.
Agalsidase beta is a recombinant form of human α-galactosidase A and is produced by recombinant DNA technology using a mammalian Chinese Hamster Ovary (CHO) cell culture. The amino acid sequence of the recombinant form, as well as the nucleotide sequence which encoded it, are identical to the natural form of α-galactosidase.
Alglucerase was a biopharmaceutical drug for the treatment of Gaucher’s disease. It was a modified form of human β-glucocerebrosidase enzyme, where the non-reducing ends of the oligosaccharide chains have been terminated with mannose residues.
Alglucosidase alfa is an enzyme replacement therapy orphan drug for treatment of Pompe disease (Glycogen storage disease type II), a rare lysosomal storage disorder (LSD). It is postulated that alglucosidase alfa will restore lysosomal GAA activity resulting in stabilisation or restoration of cardiac and skeletal muscle function (including respiratory muscles). Due to the bloodbrain barrier effect and the enzyme’s size, uptake of alglucosidase alfa in the central nervous system is unlikely.
Anethole trithione is a bile secretion-stimulating drug that restores salivation and relieves the discomfort of dry mouth in chemotherapy-induced xerostomia. In addition, this agent has exhibited chemopreventive properties. The mechanism of action to these activities have yet to be formally elucidated.
Asfotase alfa, a human recombinant tissue-nonspecific alkaline phosphatase-Fc-deca-aspartate fusion protein with enzymatic activity, promotes mineralisation of the skeleton in patients with hypophosphatasia.
Atidarsagene autotemcel is an ex vivo genetically modified autologous CD34+ hematopoietic stem and progenitor cell (HSPC) gene therapy. Autologous CD34+ HSPCs are collected from patient bone marrow (BM) harvest or from mobilised peripheral blood (mPB) and transduced with a lentiviral vector (ARSA LVV), which inserts one or more copies of the human ARSA complementary deoxyribonucleic acid (cDNA) into the cell’s genome, so that genetically modified cells become capable of expressing the functional ARSA enzyme.
Avalglucosidase alfa is a recombinant human acid α-glucosidase (rhGAA) that provides an exogenous source of GAA. Binding to M6P receptors on the cell surface has been shown to occur via carbohydrate groups on the GAA molecule, after which it is internalised and transported into lysosomes, where it undergoes proteolytic cleavage that results in increased enzymatic activity to degrade glycogen.
Betaine is a methyl derivative of glycine first isolated from the juice of sugar beets. Betaine participates in the methionine cycle, which produces vital biomolecules including proteins, hormones, phospholipids, polyamines, and nutrients. Betaine is used as a dietary supplement and has a beneficial effect on the human health. The drug acts as a methyl group donor in the remethylation of homocysteine to methionine.
Carglumic acid is a carbamoyl phosphate synthetase 1 (CPS 1) allosteric modulator. CPS1 is found in the mitochondria and is the first enzyme of the urea cycle, which converts ammonia into urea. Carglumic acid acts as a replacement for N-acetylglutamate (NAG) in N-acetylglutamate synthase (NAGS) deficiency patients by activating CPS1 but it does not help to regulate the urea cycle. Carglumic acid indicated as adjunctive therapy for the treatment of acute hyperammonemia due to the deficiency of the hepatic enzyme NAGS.
Cerliponase alfa is a recombinant form of human tripeptidyl peptidase-1 (rhTPP1). Cerliponase alfa is a proteolytic inactive proenzyme (zymogen) that is activated in the lysosome. The glycosylation profile of cerliponase alfa results in consistent cellular uptake and lysosomal targeting for activation.
Eliglustat is a potent and specific inhibitor of glucosylceramide synthase, and acts as a substrate reduction therapy (SRT) for GD1.
Elivaldogene autotemcel is indicated for the treatment of early cerebral adrenoleukodystrophy in patients less than 18 years of age, with an ABCD1 genetic mutation. Elivaldogene autotemcel adds functional copies of the ABCD1 cDNA into patients' HSCs through transduction of autologous CD34+ cells with Lenti-D LVV. Following successful engraftment with genetically modified cells, the expression of ALDP is expected to be life-long.
Elosulfase alfa is a recombinant form of human N-acetylgalactosamine-6-sulfatase (rhGALNS) used for the treatment of mucopolysaccharidosis, type IVA (Morquio A Syndrome, MPS IVA). Elosulfase alfa is intended to provide the exogenous enzyme N-acetylgalactosamine-6-sulfatase that will be taken up into the lysosomes and increase the catabolism of the GAGs KS and C6S.
Patients with MoCD Type A have mutations in the Molybdenum Cofactor Synthesis 1 (MOCS1) gene leading to deficient MOCS1A/B dependent synthesis of the intermediate substrate, cPMP. Substrate replacement therapy with fosdenopterin provides an exogenous source of cPMP, which is converted to molybdopterin. Molybdopterin is then converted to molybdenum cofactor, which is needed for the activation of molybdenum-dependent enzymes, including sulphite oxidase (SOX), an enzyme that reduces levels of neurotoxic sulphites.
Purified galsulfase, a recombinant form of human N-acetylgalactosamine 4-sulfatase, is a glycoprotein with a molecular weight of approximately 56 kD. Galsulfase is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis VI (MPS VI; N-acetylgalactosamine 4-sulfatase deficiency; Maroteaux-Lamy syndrome).
Glycerol phenylbutyrate is a nitrogen-binding medicinal product. Urea cycle disorders (UCDs) are inherited deficiencies of enzymes or transporters necessary for the synthesis of urea from ammonia (NH3, NH4+). Absence of these enzymes or transporters results in the accumulation of toxic levels of ammonia in the blood and brain of affected patients. Glycerol phenylbutyrate is indicated for use as adjunctive therapy for chronic management of patients with urea cycle disorders (UCDs).
Idursulfase (idursulfase) is a purified form of the lysosomal enzyme iduronate-2-sulfatase, produced in a human cell line providing a human glycosylation profile, which is analogous to the naturally occurring enzyme. Elaprase is indicated for the long-term treatment of patients with Hunter syndrome (Mucopolysaccharidosis II, MPS II).
Imiglucerase is a recombinant macrophage targeted acid β-glucosidase that replaces the deficient enzyme activity, hydrolysing glucosylceramide, thus correcting initial pathophysiology and preventing secondary pathology. Imiglucerase has been shown to improve both mental and physical aspects in the quality of life of Gaucher disease.
Laronidase is a recombinant form of human α-L-iduronidase and is produced by recombinant DNA technology. Laronidase is indicated for long-term enzyme replacement therapy in patients with a confirmed diagnosis of Mucopolysaccharidosis I (MPS I; α-L-iduronidase deficiency) to treat the non-neurological manifestations of the disease.
Levocarnitine as a factor is necessary in the transport of long-chain fatty acids into the mitochondria-facilitating the oxidation of fatty acids rather than their incorporation into triglycerides.
Lonafarnib is a disease modifying agent that prevents farnesylation, thereby reducing the accumulation of aberrant progerin and progerin-like proteins in the cell’s inner nuclear membrane. This results in maintaining cell integrity and normal function.
Lumasiran is a double-stranded small interfering ribonucleic acid (siRNA) that reduces levels of glycolate oxidase (GO). Decreased GO enzyme levels reduce the amount of available glyoxylate, a substrate for oxalate production. This results in reduction of urinary and plasma oxalate levels, the underlying cause of disease manifestations in patients with primary hyperoxaluria type 1 (PH1).
Mercaptamine reduces corneal cystine crystal accumulation acting as a cystine-depleting agent by converting cystine to cysteine and cysteine-cysteamine mixed disulfides.
Metreleptin mimics the physiological effects of leptin by binding to and activating the human leptin receptor, which belongs to the Class I cytokine family of receptors that signals through the JAK/STAT transduction pathway.
Migalastat is a pharmacological chaperone that is designed to selectively and reversibly bind with high affinity to the active sites of certain mutant forms of α-Gal A, the genotypes of which are referred to as amenable mutations. Migalastat binding stabilizes these mutant forms of α-Gal A in the endoplasmic reticulum and facilitates their proper trafficking to lysosomes.
Miglustat is an inhibitor of glucosylceramide synthase, the enzyme responsible for the first step in the synthesis of most glycolipids. Miglustat is indicated for the treatment of adult patients with mild to moderate type 1 Gaucher disease and for the treatment of progressive neurological manifestations in patients with Niemann-Pick type C disease.
Nitisinone is a competitive inhibitor of 4-hydroxyphenylpyruvate dioxygenase, an enzyme which precedes fumarylacetoacetate hydrolase in the tyrosine catabolic pathway. By inhibiting the normal catabolism of tyrosine in patients with hereditary tyrosinemia type 1 (HT-1), nitisinone prevents the accumulation of the toxic intermediates maleylacetoacetate and fumarylacetoacetate.
Olipudase alfa is a recombinant human acid sphingomyelinase that reduces sphingomyelin (SM) accumulation in organs of patients with Acid Sphingomyelinase Deficiency (ASMD).
Pegvaliase is a PEGylated recombinant phenylalanine ammonia lyase enzyme that converts phenylalanine to ammonia and trans-cinnamic acid that are primarily eliminated by liver metabolism. It is indicated for the treatment of patients with phenylketonuria (PKU).
Sacrosidase is a liquid enzyme preparation derived from baker’s yeast (Saccharomyces cerevisiae) used for the treatment of genetically determined sucrase deficiency, which is part of congenital sucrase-isomaltase deficiency (CSID).
Sapropterin is a synthetic version of the naturally occurring 6R-BH4, which is a cofactor of the hydroxylases for phenylalanine, tyrosine and tryptophan. The rationale for administration of sapropterin in patients with BH4-responsive PKU is to enhance the activity of the defective phenylalanine hydroxylase and thereby increase or restore the oxidative metabolism of phenylalanine. The rationale for administration of sapropterin in patients with BH4 Deficiency is to replace the deficient levels of BH4, thereby restoring the activity of phenylalanine hydroxylase.
Sebelipase alfa is a recombinant human lysosomal acid lipase (rhLAL). Replacement of LAL enzyme activity leads to reductions in liver fat content and transaminases, and enables metabolism of cholesteryl esters and triglycerides in the lysosome, leading to reductions in lowdensity lipoprotein (LDL) cholesterol and non-high-density lipoprotein (HDL) cholesterol, triglycerides, and increases in HDL cholesterol. Improvement in growth occurs as a result of substrate reduction in the intestine.
Sodium phenylbutyrate is a pro-drug and is rapidly metabolised to phenylacetate. Phenylacetate is a metabolically active compound that conjugates with glutamine via acetylation to form phenylacetylglutamine which is then excreted by the kidneys. On a molar basis, phenylacetylglutamine is comparable to urea (each containing 2 moles of nitrogen) and therefore provides an alternate vehicle for waste nitrogen excretion.
Taliglucerase alfa, a long term enzyme replacement therapy, is a recombinant analog of human lysosomal glucocerebrosidase that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide, reducing the amount of accumulated glucocerebroside. It is used for the treatment of patients with a confirmed diagnosis of Type 1 Gaucher disease.
Teduglutide is an analogue of GLP-2. The naturally occurring human glucagon-like peptide-2 (GLP-2) is a peptide secreted by L cells of the intestine which is known to increase intestinal and portal blood flow, inhibit gastric acid secretion, and decrease intestinal motility. In several nonclinical studies, teduglutide has been shown to preserve mucosal integrity by promoting repair and normal growth of the intestine through an increase of villus height and crypt depth.
Both the prodrug (telotristat ethyl) and its active metabolite (telotristat) are inhibitors of L-tryptophan hydroxylases (TPH1 and TPH2, the rate limiting steps in serotonin biosynthesis). Serotonin plays a critical role in regulating several major physiological processes, including secretion, motility, inflammation, and sensation of the gastrointestinal tract, and is over-secreted in patients with carcinoid syndrome. Through inhibition of peripheral TPH1, telotristat reduces the production of serotonin, thus alleviating symptoms associated with carcinoid syndrome.
Trientine is a copper-chelating agent whose principal mechanism of action is to eliminate absorbed copper from the body by forming a stable complex that is then eliminated through urinary excretion. Trientine may also chelate copper in the intestinal tract and so inhibit copper absorption.
Uridine triacetate is an acetylated form of uridine. Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation. It is indicated in patients with hereditary orotic aciduria who cannot synthesize adequate quantities of uridine due to a genetic defect in uridine nucleotide synthesis.
Velaglucerase alfa supplements or replaces beta-glucocerebrosidase, the enzyme that catalyzes the hydrolysis of glucocerebroside to glucose and ceramide in the lysosome, reducing the amount of accumulated glucocerebroside and correcting the pathophysiology of Gaucher disease. Velaglucerase alfa increases haemoglobin concentration and platelet counts and reduces liver and spleen volumes in patients with type 1 Gaucher disease.
Velmanase alfa is a recombinant form of human alpha-mannosidase. Velmanase alfa is intended to supplement or replace natural alpha-mannosidase, an enzyme that catalyses the sequential degradation of hybrid and complex high-mannose oligosaccharides in the lysosome, reducing the amount of accumulated mannose-rich oligosaccharides.
Vestronidase alfa is a recombinant form of human betaglucuronidase (GUS) and is intended to provide exogenous GUS enzyme for uptake into cellular lysosomes and subsequent catabolism of accumulated glycosaminoglycans (GAGs) in affected tissues.
The active moiety in zinc acetate is zinc cation, which blocks the intestinal absorption of copper from the diet and the reabsorption of endogenously secreted copper.