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Showing posts from July, 2011

Meetings: SMR Recent Disclosures of Clinical Candidates

One of the best UK meetings I try to go to is the annual Society of Medicines Research (SMR) meeting on recent clinical candidates. This year, it is being held on Thursday 8th December 2011, the the NHLI in London, further details are here. Compounds covered include: OSI-906, AZD-4547, fostamatinib, POL-7080, and AFQ-056, amongst others.

Internship - Scientific Data Visualisation

New Drug Approvals 2011 - Pt. XXIII Ticagrelor (BrilintaTM)

ATC Code:B01AC24
Wikipedia:Ticagrelor

On July 20th, 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. This drug is the first reversi…

New Drug Approvals 2011 - Pt. XXII Indacaterol Maleate (ArcaptaTM)

ATC Code:R03AC18
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 the lungs. Activation of the beta…

New Drug Approvals 2011 - Pt. XXI Rivaroxaban (XareltoTM)

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 CELFTRKLCSLDNGDCDQFCHEEQNSVVCSCARGYTLADNGKACIPTGPYPCGKQTLERR KRS…