The ChEMBL-og

ATC Code: A06AH03 Wikipedia:  Naloxegol ChEMBL:  CHEMBL2219418 On September 16th  FDA approved  Movantik (naloxegol, AZ-13337019 ), as an oral treatment for patients with opioid-induced constipation and chronic non-cancer pain. Naloxegol Naloxegol is an opioid receptor antagonist .  Due to its similarity to noroxymorphone, a main metabolite of oxycodone , naloxegol is classed as a controlled substance. However, the FDA analysed its abuse potential and concluded that there was no risk of dependency. Mode of Action Opioids are a class of drugs which are used to manage pain, but have a common side effect of reducing the motility of the gastrointestinal tract, making bowel movements difficult.  Opioids work by binding to the mu-receptors ( CHEMBL233 , UniProt:P35372 ) in the central nervous system, thereby reducing pain. However, they are also able to bind to the mu-receptors in the gastrointestinal tract, hence causing op...

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:  Unavailable Wikipedia:   Droxidopa ChEMBL:  CHEMBL2103827 On February 18th the  FDA approved  Droxidopa (tarde name Northera™) for the treatment of neurogenic orthostatic hypotension (NOH). NOH is a rare, chronic and often debilitating drop in blood pressure upon standing, and is associated with Parkinson's disease, multiple-system atrophy, and pure autonomic failure. Symptoms of NOH include dizziness, light-headedness, blurred vision, fatigue and fainting when a person stands.  Target(s) Droxidopa (also known as L-DOPS, L-threo-dihydroxyphenylserine, and SM-5688) is a prodrug which can be converted to norepinephrine (noradrenaline) by  Aromatic L-amino acid decarboxylase  ( Uniprot P20711  ;  EC 4.1.1.28 ). Norepinephrine in turn can be converted to epinephrine by  Phenylethanolamine N-methyltransferase  ( Uniprot P11086  ). Droxidopa can cross the blood brain barrier, contrary to e...

ATC code :  R03AL03 Wikipedia :  Umeclidinium bromide  (and  vilanterol ) ChEMBL :  CHEMBL1187833  (and  CHEMBL1198857 ) On December 18, 2013, the FDA approved Anoro Ellipta for the once-daily, long-term maintenance treatment of airflow obstruction in patients with obstructive pulmonary disease (COPD). Anoro is a combination of umeclidinium (62.5 mcg - more details below) and vilanterol inhalation powder (25 mcg -  already approved in a different formulation ). Ellipta is the single inhaler device: The majority of COPD cases are due to cigarette smoking and this lung disease is a leading cause of death in the United States. Patients affected by COPD experience breathing difficulties worsening with the time as well as chronic cough and chest tightness. Umeclidinium Umeclidinium (also known as umeclidinium bromide, GSK573719A and GSK573719) is a small molecule with a molecular weight of ...

ATC Code: N05CH Wikipedia: Tasimelteon On January 31 st  2014, the FDA approved Tasimelteon (Tradename: Hetlioz ; Research Code(s): VEC-162, BMS-214778), a melatonin receptor agonist , for the treatment of Non-24-hour sleep-wake disorder (Non-24). Non-24-hour sleep–wake disorder (Non-24) is a chronic circadian rhythm sleep disorder, mostly affecting blind people. It is characterised by insomnia or excessive sleepiness related to abnormal synchronization between the 24-hour light–dark cycle and the endogenous circadian cycle (slightly longer than 24 hours). This deviation can be corrected by exposure to solar light, which resets the internal clock, however, the loss of photic input, and the absence of light perception in the majority of patients, prevents them from drifting back into normal alignment. Tasimelteon is an agonist at melatonin MT1 and MT2 receptors , with a relative greater affinity for MT2. These receptors are thought to be involved in the control...

ATC code (stem): J05AB Wikipedia: Sofosbuvir ChEMBL: CHEMBL1259059 On December 6, 2013, the FDA approved sofosbuvir for the treatment of patients with chronic hepatitis C infection. Sofosbuvir is intended for use as a component in combination treatments, depending on the type of hepatitis C either alongside Ribavirin alone, or in combination with both Ribavirin and peginterferon-alpha . Earlier in 2013, the FDA had already approved Simeprevir for the treatment of this condition. Hepatitis C is an infectious disease that affects primarily the liver and is caused by the hepatitis C virus (HCV), which belongs to the family of Flaviviridae and has a positive sense single stranded RNA genome of 9,600 nucleotides . Infection is mainly by blood-to-blood contact, through sharing or reuse of syringes or unsterilized medical equipment. Initially, the infection progresses without symptoms, and only becomes apparent in the chronic stages when liver damage leads to symptom...

    wikipedia:   bazedoxifene              ATC code:   G03XC02 On 3 October 2013, FDA approved  a new drug,   bazedoxifene in combination with estrogen (trade name  DUAVEE™ ), for treatment of moderate-to-sever vasomotor symptoms (hot flashes) associated with menopause and the prevention of postmenopausal osteoporosis in women. Bazedoxifene reduces the risk of excessive growth of the uterus (endothermetrial hyperplasia) that can be caused by estrogen. Bazedoxifene (IUPAC name: 1-{4-[2-(Azepan-1-yl)ethoxy]benzy}-2-(4-hydroxyphenyl}-3-methyl-1H-indole-5-ol)  is an  indole based small molecule of molecular weight of 470.6 g/mol, polar surface area of 57.9, seven rotatable bonds, four hydrogen bond acceptors and one hydrogen bond donor. The compound is lipophilic with alogP 7.22, ApKa 10.12 and logD of 5.17.  The compound  is also known as WAY-140424, Bazedoxifene...

Wikipedia: Eslicarbazepine Acetate On November 8th 2013, FDA approved Eslicarbazepine Acetate (tradename: Aptiom ; research codes: Sep-0002093, BIA 2-093; ChEMBL: CHEMBL87992 ), a prodrug indicated as adjunctive treatment of partial-onset seizures associated with epilepsy . Epilepsy is neurological disorder characterised by abnormal neuronal activity in the brain. Partial-onset seizures, as opposed to generalised seizures , affect initially only one part of the brain and, depending on the part of the brain that is affected, these seizures will present different symptoms. Eslicarbazepine (ChEMBL: CHEMBL315985 ), the bioactive ingredient of the prodrug Eslicarbazepine Acetate, exerts its anticonvulsant activity by blocking the voltage-gated sodium channel (VGSC) . VGSC has 3 distinctive states: the resting state, during which the VGSC is closed but responsive to a depolarisation impulse, the open state, during which the channel is open allowing the sodium ion to enter the cel...

ATC Code: J05AE14 Wikipedia: Simeprevir On November 22 th  2013, the FDA approved simeprevir (Tradename: Olysio ; Research Code(s): TMC-435; TMC435350), a Hepatitis C virus NS3/NS4A protease  (HCV NS3/NS4A) inhibitor, for the treatment of chronic hepatitis C virus genotype 1  infection, in combination with peginterferon alfa and ribavirin . Chronic hepatitis C is a prolonged infection that affects the liver and is caused by a small single-stranded RNA virus , which is transmitted by blood-to-blood contact. Chronic hepatitis C is normally asymptomatic, but may lead to liver fibrosis, and thus liver failure. Simeprevir is an inhibitor of the hepatitis C virus (HCV) serine protease NS3/NS4A (ChEMBLID: CHEMBL2095231 ; Uniprot ID: A3EZI9 , D2K2A8 ; Pfam: PF02907 ), a viral protein complex required for the proteolytic cleavage of the HCV encoded polyprotein (UniProt: P27958 ) into mature forms of the NS4B, NS5A and NS5B proteins. These proteins are involved...

ATC Code:  C02KX   (incomplete) Wikipedia:   Macitentan ChEMBL:  CHEMBL2103873 On October 13th the  FDA approved   Macitentan  (trade name Opsumit  ® ) for the treatment of pulmonary arterial hypertension (PAH). Macitentan is an endothelin receptor antagonist (with affinities to both Endothelin ET-A (ETA) and Endothelin ET-B (ETB) receptor subtypes, similar in mechanism of action to the previously licensed drug Bosentan , CHEMBLID957 ). Target(s) The Endothelin receptor ET-A (ETA, CHEMBLID252  ; Uniprot P25101 ) and Endothelin receptor ET-B (ETB, CHEMBLID1785  ; Uniprot P24530 ) receptors mediate a number of physiological effects via the natural peptide agonist Endothelin-1 (ET1 , CHEMBL437472  ; Uniprot P05305 ). In addition to normal roles in supporting homeostasis, these effects can include pathologies such as inflammation, vasoconstriction, fibrosis and hypertrophy. Macitentan acts as an antagoni...

ATC code: not yet assigned Wikipedia: Riociguat On October 8, 2013, the FDA approved riociguat for the treatment of patients suffering from two forms of pulmonary hypertension - chronic thromboembolic pulmonary hypertension (CTEPH), and pulmonary arterial hypertension (PAH). Pulmonary hypertension (PH) is a disease characterized by abnormally high blood pressure in the lungs, which increases the workload for the right ventricle of the heart. Some of the symptoms of PH are dizziness, shortness of breath and water deposits in the legs and joints. PH progresses slowly and can lead to severe and often fatal circulatory and respiratory complications. CTEPH is a form of PH caused by blood clots obstructing the passage of blood through the vessels in the lung, often after a pulmonary embolism has occurred. PAH on the other hand is caused by a chronic tightening or constriction of blood vessels. Riociguat ( CHEMBL2107834 ) is a stimulator of soluble guanylate cyclase (sGC),...

ATC Code: N06AX26 Wikipedia: Vortioxetine On September 30th 2013, FDA approved Vortioxetine (as the hydrobromide salt; tradename: Britellix ; research code: Lu AA21004 (Lu AA21004 (HBR) for the hydrobromide salt); ChEMBL: CHEMBL2104993 ), a multimodal antidepressant indicated for the treatment of major depressive disorder (MDD) . MDD is a mental disorder characterised by low mood and/or loss of pleasure in most activities, and by symptoms or signs such as increased fatigue, change in appetite or weight, insomnia or excessive sleeping and suicide attempts or thoughts of suicide. MDD is believed to arise from low levels of neurotransmitters (primarily serotonin (5-HT), norepinepherine (NE) and dopamine(DA)) in the synaptic cleft between neurons in the brain. Several antidepressants for the treatment of MDD are already available in the market and its choice depends on which symptoms need to be tackled. The most important classes of antidepressants include the Selective Serotonin ...

ATC code: J05AX12 On 12 August, the FDA approved a further drug for the treatment of HIV-1 infection, Dolutegravir (Tradename: Tivicay). Dolutegravir also known as S/GSK-1349575, is an HIV-1 integrase inhibitor. The drug has been approved for treatment of treatment-naïve as well as treatment-experienced HIV-infected adults including those who have been treated with other integrase inhibitors. In addition, Dolutegravir can be used for the treatment of children aged 12 years or older and weighing at least 40kg who have not been treated with integrase inhibitors, but are either treatment-naïve or treatment –experienced. HIV, a lentivirus , infects vital cells in the human immune system such as helper T. cells (CD4+ T cells) and macrophages. The disease is responsible for millions of death every year, especially in Sub-Saharan Africa where treatment complications are enhanced by co-infection with tuberculosis and poverty. The approval of a new antiviral agent like Dolutegr...

ATC Code:  N07XX09   (2014) Wikipedia:   Dimethyl Fumerate ChEMBL:  CHEMBL2107333 On March 27th the  FDA approved   Dimethyl Fumarate  (DMF, trade name  TECFIDERA ™) for the treatment of adults with relapsing forms of multiple sclerosis (MS). DMF and the metabolite, monomethyl fumerate (MMF), activate the Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway via inhibition of Kelch-like ECH-associated protein 1 (KEAP1, cytosolic inhibitor of Nrf2).  Target(s) The KEAP1 ( CHEMBL2069156 ) is a naturally occuring cytosolic inhibitor of Nrf2 and DMF/MMF acts through chemical modification of KEAP1. The NrF2 pathway is the primary cellular defence against the cytotoxic effects of oxidative stress . After translocation to the nucleus, Nrf2 heterodimerizes with MafF, MafG, and MafK . The combined heterodimer binds to antioxidant/electrophile response element ( ARE/EpRE ) and subsequently initiates transcription o...