The ChEMBL-og

ATC Code: L01XX47 Wikipedia: Idelalisib ChEMBL: CHEMBL2216870 On July 23rd the FDA approved Zydelig ( idelalisib , GS-1101), as an orally-delivered drug to treat patients with three types of blood cancers. • Relapsed chronic lymphocytic leukemia (CLL) • Relapsed follicular B-cell, non-Hodgkin lymphoma  (FL) • Relapsed small lymphocytic lymphoma (SLL) Blood cancer The three main categories of blood cancer are leukemia , lymphoma and myeloma . Lymphoma is also split into two types: Hodgkin lymphoma and non-Hodgkin lymphoma . Both leukemia and myeloma occur in the bone marrow , whilst lymphoma is a cancer that is isolated to the lymphatic system. Acute leukemia is where there is an abundance of underdeveloped white blood cells that can’t function properly and chronic leukemia is where there are just far too many white blood cells, which is just as bad as having too few. Myeloma is where the plasma cells form tumours in the bone marrow. ...

  ATC code: A16AB12 ChEMBL: CHEMBL2108676 On February 14, 2014, the FDA approved elosulfase alfa for the treatment of Mucopolysaccharidosis Type IVA (Morquio A syndrome). Elosulfase alfa is intended to replace the missing GALNS enzyme involved in an important metabolic pathway. Absence of this enzyme leads to problems with bone development, growth and mobility. Mucopolysaccharidoses comprise a group of lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAG). Mucopolysaccharidosis IVA (MPS IVA, Morquio A Syndrome) is characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The sulfatase activity deficiency resultsin the accumulation of the GAG substrates, KS and C6S, in the lysosomal compartment of cells throughout the body. The accumulation leads to widespread cellular, tissue, and organ dysfunction. It is a rare autosomal recessive disea...

On October 17, the FDA approved Ocriplasmin (tradename: Jetrea ; Research Code: Microplasmin), a proteolytic enzyme indicated for the treatment of symptomatic vitreomacular adhesion (VMA) . VMA is a condition of the eye that results from the liquefaction of the vitreous gel within the human eye and consequent adhesion to the retina . As the eye ages, the vitreous humor can naturally separate from the retina. However, if the separation is not complete, areas of adhesion can occur. The traction from these adhesion areas on the retinal surface is the underlying pathology of symptomatic VMA, which can lead to ocular damage. Ocriplasmin is the first drug approved to treat this condition and it exherts its therapeutic action by selectively breaking down the three major protein components, fibronectin , laminin and collagen , of the vitreous body and vitreoretinal interface, and thereby dissolving the protein matrix responsible for VMA. The only alternative treatment is a surgica...

ATC code :   A16AB11 Wikipedia : Taliglucerase alfa   On May 1, the FDA approved taliglucerase alfa for the treatment of Type I Gaucher's disease. Gaucher's disease is the most common of the lysosomal storage diseases . It is a hereditary disease caused by a deficiency of the enzyme β- glucocerebrosidase (Uniprot: P04062 ), also called β-Glucosidase. Gaucher's disease is a rare genetic disease with an incidence of 1 in 50,000 births and is considered an orphan disease. Type I Gaucher's disease is about 100 times more common in people of Ashkenazi jewish descent compared a north American population. Symptoms of type I Gaucher's disease begin typically in early adulthood and include enlarged liver and grossly enlarged spleen, impaired bone structure, anemia and low platelet levels, leading to prolonged bleeding and easy bruising. If enzyme replacement therapy (ERT) is available, the prognosis for patients with type I Gaucher's disease is good. ...

ATC code: V03AF09 The first FDA new drug approval of 2012 is Glucarpidase, approved on Jan 17th 2012. Glucarpidase (tradename: Voraxaze ; formerly known as carboxypeptidase-G2 or CPG2) is a carboxypeptidase enzyme indicated for the treatment of toxic plasma methotrexate (MTX) concentrations ( > 1 umol/L) in patients with delayed MTX clearance due to impaired renal function. MTX (ChEMBL: CHEMBL426 ) is an antifolate drug and is one of the most widely used anticancer agents. Unlike other anticancer agents, MTX can be safely administrated over a wide dose range. However, during treatment with high doses of MTX, patients may develop renal dysfunction. Since MTX is primarily cleared by renal excretion, this will lead to toxic levels of MTX. Glucarpidase acts by converting MTX to its inactive metabolites 2,4-diamino-N 10 -methylpteroic acid (DAMPA) and gluta mic acid, providing thus an alternate route of elimination to renal excretion. Glucarpidase (Unipr...

ATC code : L01XX02 On November 18, the FDA approved asparaginase from  Erwinia chrysanthemi for the treatment of patient with acute lymphoblastic leukemia (ALL) who have become allergic to the E. coli asparaginase that is conventionally used for the treatment of ALL patients. ALL is a cancer of the white blood cells and can be fatal within weeks from the onset of the disease if it is left untreated. In ALL, there is an unproportional increase in the population of immature white blood cells, which crowd out functional immune cells as well as red blood cells and platelets, and in advanced stages of the disease infiltrate into tissues and organs, most frequently liver, spleen and lymph nodes. The symptoms of ALL in its initial stages are fatigue, anemia, frequent infections and fever as well as breathlessness and prolonged bleeding. ALL is caused by DNA damage and associated with exposure to radiation and cancerogenic chemicals. There are a number of typical chromosoma...

ATC code : B02BD07 On February 17 th 2011, the FDA approved human coagulation Factor XIII (FXIII) Concentrate as an orphan drug under the trade name Corifact (ATC code B02BD07 ) to treat congenital Factor XIII deficiency  (OMIM: 134570  and OMIM: 134580 , ICD-10:D68.2). The incidence of this rare condition is 1 in 1 to 5 million, making it the rarest form of hemophilia . The genetic deficiency leads to defective fibrin crosslinking, the terminal step of the coagulation cascade which leads to blood forming clots to deplete its loss from damaged vessels. Prior to US approval, FXIII Concentrate had already been marketed in Europe, as Fibrogammin P ,  developed by CSL Behring of Marburg, Germany. Recently, recombinant FXIII (rFXIII, Novo Nordisk, Bagsværd, Denmark) has completed phase 3 clinical trials. FXIII exists naturally as a secreted, tetrameric protein (with composition A2B2) with a molecular weight of ca. 320 kDa. The tetramer consists of twice...

ATCC:  M04AX02 On September 14th 2010, the FDA approved Pegloticase under the trade name Krystexxa. Pegloticase is a recombinant enzyme for the treatment of gout and can replace xanthine oxidase (XO) inhibitors for patients who do not respond to or cannot tolerate treatment with xanthine oxidase inhibitors.  Gout is a painful affliction caused by microscopic needle-shaped crystals of sodium urate which precipitate in joints and tendons and stimulate a local inflammatory response. These attacks of inflammatory arthritis not only cause pain and stiffness of the joint, but, if left untreated for years, also damage the cartilage and surrounding tissue. Hard, non-painful deposits of crystalline uric acid known as tophi occur in the joints and sometimes the kidney.  Gout is generally associated with obesity, hypertension, insulin resistance and hyperlipidaemia. In more than half of the cases of diagnosed gout, patients have elevated blood levels of uric acid. Conve...

ATC code: A16AB10 On 26th February, FDA has approved Velaglucerase Alfa, under the trade name VPRIV. Velaglucerase Alfa, is a hydrolytic lysosomal glucocerebroside-specific enzyme indicated for long-term enzyme replacement therapy (ERT) for patients with type 1 Gaucher disease . Gaucher's disease is an autosomal recessive disorder characterized by a deficiency of the lysosomal enzyme beta-glucocerebrosidase (UniProt: P04062 ) ( E.C. 3.2.1.45 ) (this enzyme is also known as glucosylceramidase, β-glucosidase, and D-glucosyl-N-acylsphingosine glucohydrolase). Velaglucerase Alfa ATC code is A16AB10. Glucocerebrosidase catalyses the hydrolysis of the glycolipid glucocerebroside , which is an intermediate in the glycolipid metabolism. Deficiency in this enzyme causes accumulation in the liver, spleen, bones, bone marrow and nervous system and can prevent cells and organs from working properly. Velaglucerase Alfa works by catalysing the hydrolysis of glucocerebroside, reducing...