The ChEMBL-og

Here's the equivalent view of drug approvals for 2011 so far - pretty similar picture in terms of the distribution of molecule classes - but remember this set of drug approvals, got their USANs assigned, on average about 3 to 4 years ago, so the sets are not strictly comparable, and of course, suffer from small absolute numbers....

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 (partial): S01LA On November 18th 2011, the FDA approved Aflibercept (trade name: Eylea ; Research Code: AVE-0005,  also known as VEGF Trap), a recombinant fusion protein indicated for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD) . AMD is an eye condition which usually occurs in older patients and affects the macula area of the retina, causing loss of vision and eventually blindness. In particular, wet AMD is characterised by an abnormal growth of new blood vessels ( neovascularisation ) behind the retina. This originates from an abnormal activation of angiogenesis, by the vascular endothelial growth factor-A (VEGF-A; ChEMBL: CHEMBL1783 ; Uniprot: P15692 ) and the placenta growth factor (PlGF; ChEMBL: CHEMBL1697671 ; Uniprot: P49763 ), of the vascular endothelial growth factor receptors VEGFR-1 (ChEMBL: CHEMBL1868 ; Uniprot: P17948 ) and VEGFR-2 (ChEMBL: CHEMBL279 ; Uniprot: P35968 ), two receptor tyrosi...

ATC Code: L01XE18 Wikipedia: Ruxolitinib On November 16th 2011, the FDA approved ruxolitinib phosphate (Tradename: Jakafi ™ Research Code: INCB-018424), a JAK1/JAK2 inhibitor for the treatment of patients with intermediate or high-risk myelofibrosis , including primary myelofibrosis, post-polycythemia vera myelofibrosis and post-essential thrombocythemia myelofibrosis. Myelofibrosis is a disorder of the bone marrow, in which the marrow is replaced by scar (fibrous) tissue. Scarring of the bone marrow reduces its ability to blood cells, and can lead to anemia, bleeding problems, and a higher risk of infections due to reduced white blood cells. It is also associated with engorgement of organs suchs as the spleen and liver. Primary myelofibrosis may develop to secondary myelofibrosis - including leukemia and lymphoma. Myelofibrosis is associated with dysregulated Janus kinases JAK1 and JAK2, and some with a somatic mutation in JAK2 (JAK2V617F) ( OMIM ). JAK signalin...

ATC Code: N05BA09 Wikipedia: Clobazam On October 24 th , the FDA approved Clobazam (Tradename: Onfi TM ; Research Code: RU-4723), a GABA A receptor agonist, for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome ( LGS ) in patients aged two years or older. Lenox-Gastaut syndrome is a rare and severe form of epilepsy that is typically diagnosed in childhood and often persists into adulthood. LGS accounts for 1-4% of childhood epilepsies, and it is associated with multiple types of seizures, as well as, daily periods of frequent seizures. Clobazam decreases the frequency of the LGS seizures by potentiating GABAergic neurotransmission, trough the binding of the GABA A receptor at the benzodiazepine site. GABA A receptor is a protein complex of five subunits (mainly α2β2γ) located in the synapses of neurons. All GABA A receptors contain an ion channel that conducts chloride ions across neuronal cell membranes and two binding sites fo...

  ATC code  V03AC02   Wikipedia Deferiprone On October 14th, 2011 FDA announced the approval of Deferiprone ( trade name : Ferriprox TM ) for the treatment of iron overload which is potentially fatal in patients with thalassemia . Deferiprone is an oral iron chelating agent, binding excess iron in the blood and thus making it available to excretion from the body. Thalassaemia is a inherited (mostly autosomal recessive) blood disease that can lead to anemia by causing the formation of abnormal hemoglobin molecules not able to properly bind and release oxygen. Thalassaemia (OMIM: 141800 (α-) / 141900 (β-)) is sub-classified according to which of the subunits of the hetero-tetrameric (2α/2β, UniProt: P69905 / P68871 ) hemoglobin is affected, contrary to sickle-cell anaemia (OMIM: 603903 ) which results exclusively from a specific mutation in the β subunit. The primary treatment of thalassaemia major, the severe form of β-thalassaemia, requires frequent blood...

ATCC: C01EB19 Wikipedia: Icatibant On the August 25th 2011, the FDA approved Icatibant (trade name: Firazyr TM ), a bradykinin B2 receptor (B2R) antagonist indicated for the treatment of acute attacks of hereditary angioedema (HAE) in patients aged 18 or older. HAE is a rare genetic disease and is caused by low levels of C1-esterase inhibitor (C1-INH) , the major endogenous inhibitor and regulator of the protease plasma kallikrein and the key regulator of the Factor XII/kallikrein cascade. One component this cascade is the production of bradykinin by plasma kallikrein. During HAE attacks, disregulated activity of plasma kallikrein leads to excessive bradykinin production; bradykinin is a potent vasodilator, which s thought to be responsible for the characteristic HAE symptoms of localised swelling, inflammation and pain. Icatibant treats the clinical symptoms of HAE attack by selective- and competitively binding, as an antagonist, to the B2 bradykinin receptor (B2...

ATCC: L01XE15 Wikipedia: Crizotinib On the August 26th 2011, the FDA approved crizotinib (trade name: Xalkori ® Research code: PF-02341066), an anaplastic lymphoma kinase (ALK) inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer ( NSCLC ) that is ALK-positive as detected by an approved FDA-approved test. Non-small cell lung carcinomas (NSCLC) are cancers of the epithelial cells in the lung and describe all types of lung carcinomas other than small cell carcinomas. NSCLCs make up 88% of all lung carcinomas (see Cancer Research UK pages ) and comprise genetically distinct classes of cancer, the most common are: Lung adenocarcinoma, large cell carcinoma and squamous cell carcinoma. Across the NSCLC types, some tumors harbour an ALK fusion protein. The EML4-ALK fusion gene has been shown to be affect the outcome of drug response and cells show resistance to EGFR inhibitors. C rizotinib is an orally-dosed recep...

ATC code:  L01XE15 Wikipedia : Vemurafenib On the August 17th 2011, the FDA approved Vemurafenib (trade name: Zelboraf TM Research code: PLX-4032, RG-7204 and RO-5185426), a BRAF kinase inhibitor for the treatment of patients with unresectable or metastatic melanoma carrying the mutant BRAF V600E . Melanoma is a malignant tumor of melanocytes (skin cells that produce melanin) and is an aggressive disease responsible for an estimated 50,000 deaths worldwide. Over 50% of patients with advanced melanoma carry an activating mutation in the Serine/Theronine protein kinase: BRAF (V600E). The MAPK signal transduction pathway is an important and frequently mutated pathway in cancer. A wide variety of growth factors signal through this pathway, via RAS and RAF proteins to cause cell proliferation. The activating mutation in BRAF causes activation of this pathway downstream of BRAF regardless of the presence of growth factor (the signalling pathway is 'dysregulated...

ATC code:L01XC12 On 19th August 2011, the FDA approved Brentuximab vedotin (trade name Adcetris TM , ATC code:L01XC12, research code:SGN-35, aAC10-vcMMAE), a  antibody drug conjugate (ADC) targeting CD-30, indicated for the treatment of patients with Hodgkin's lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates (1.1); and the treatment of patients with systemic anapaestic large-cell lymphoma after failure of at least one prior multi-agent chemotherapy regimen. Hodgkin's lymphoma is a cancer of cells derived from white blood cells called lymphocytes . In Hodgkin's lymphoma, the disease spreads from one lymph node group to another, and then leads to more systemic effects. Hodgkin's lymphoma can be treated with radiation therapy, chemotherapy or autologous hematopoietic stem cell transplantation. The occurrence of the disease shows tw...

ATC Code: B01AC24 Wikipedia: Ticagrelor On July 20 th , the FDA approved Ticagrelor (Tradename: Brilinta ; Research Code: AZD-6140, NDA 022433), a purinergic receptor P2Y12 platelet antagonist indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) . Acute coronary syndrome is often the initial presentation of an individual manifesting coronary artery disease (CAD). ACS can present as unstable angina , non-ST elevation myocardial infarction , or ST elevation myocardial infarction . Typically, ACS begins with the rupture or erosion of a vulnerable plaque in a coronary artery, which results in the exposure of elements under the endothelial layer, such as collagen or von Willebrand factor, to circulating blood. These ligands trigger a series of responses, including platelet adhesion, activation, and aggregation. Ticagrelor reduces the thrombotic risk in ACS by blocking the P2Y12 receptor on the platelet surface...

ATC Code: R03 AC18 On July 1, the FDA approved indacaterol maleate (NDA 022383) for the long-term treatment of patients with chronic obstructive pulmonary disease ( COPD ) a chronic and serious disease involving restriction of full lung function. The narrowing of airways of COPD is irreversible, and follows inflammation in the lung, believed to be linked to environmental pollutants such as tobacco smoke, workplace dusts and urban air pollution. Indacaterol maleate is administered as an aerosol through a dry powder inhaler and carries a boxed warning for asthma-related death and is not indicated for the treatment of asthma. The active ingredient of indacaterol maleate is indacaterol (ChEMBL: 1095777 ) an agonist of the beta-2 adrenergic receptor (Uniprot: P07550 , ChEMBL: 210 ) with measured EC50 of 11nM. Indacaterol exerts its effect through activation of the beta-2 adrenergic receptor, leading to smooth muscle relaxation and a widening of bronchioli in t...

ATC code:   B01AX06 On July 1st, FDA approved Rivaroxaban (trade name:  Xarelto , Research code: BA-59-7939, NDA 022406), an anti-coagulant to prevent deep vein thrombosis (DVT) in patients with knee or hip replacement surgery. Rivaroxaban is the first orally applied direct inhibitor of Factor Xa (FXa), a key regulatory of the coagulation cascade . In DVT, a blood clot is formed which can dislodge and travel to the lungs, causing pulmonary embolism which can be potentially fatal. Factor Xa (EC number 3.4.21.6 , UniProt ID P00742 , OMIM 613872 ) is a serine endopeptidase , cleaving prothrombin into its active form, thrombin , which then activates further downstream factors which ultimately lead to platelet activation and fibrin formation, clotting the damaged blood vessels. The sequence of Factor X is >Factor X MGRPLHLVLLSASLAGLLLLGESLFIRREQANNILARVTRANSFLEEMKKGHLERECMEE TCSYEEAREVFEDSDKTNEFWNKYKDGDQCETSPCQNQGKCKDGLGEYTCTCLEGFEGKN CELFTRKLCSLD...