The ChEMBL-og

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...

ATC Code: D01AC   (incomplete) Wikipedia:  Not Available ChEMBL:  CHEMBL2105689 On November 14th the  FDA approved  Luliconazole (trade name Luzu  TM ) for the treatment of skin fungal infections including ringworm. Luliconazole inhibits fungal synthesis of ergosterol, required for fungal cell membranes, by inhibiting the enzyme cytochrome P450 14-alpha-demethylase (P45014DM) .   Target(s) Like all azole antifungals, Luliconazole binds and inhibits fungal 14-alpha-demethylase (e.g. CHEMBL1681624 , Uniprot Q96W81 ).  P45014DM is a cytochrome P450 that catalyses the oxidative removal of the 14α-methyl group from eburicol to ergosterol. Azoles bind to the haem in P45014DM  via the unprotonated N atom and occupy the active site as non-competitive inhibitors. Luliconazole ( CHEMBL2105689 ;  Pubchem :  144206495  ) is a small molecule drug with a molecular weight of 35...

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: Wikipedia: Ibrutinib On November 13, 2013, the FDA approved Ibrutinib (Imbruvica TM ) for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. MCL is a subtype of B-cell lymphoma and accounts for 6% of non-Hodgkin's lymphoma cases. In an open-label, multi-center, single-arm trial of 111 previously treated patients, Ibrutinib showed a 65.8% response rate. Ibrutinib is an irreversible inhibitor of the Tyrosine-protein kinase BTK (Uniprot:Q06187; ChEMBL: CHEMBL5251 ; canSAR target synopsis ) and is the first approved targeted BTK inhibitor. It forms a covalent bond with a cysteine residue via a Michael acceptor mechanism, in the BTK active site, leading to inhibition of BTK enzymatic activity Ibrutinib (ChEMBL: CHEMBL1873475 ; canSAR drug synopsis ; also known as CRA-032765 and PCI-32765) has the formula C25H24N6O2 and a molecular weight 440.50. It is absorbed after oral administration with a median Tma...

ATC Code:  L01XC15 Wikipedia: Obinutuzumab On November 1, 2013 the FDA approved obinutuzumab (Gazyva TM ) for use in combination with chlorambucil  (a nitrogen mustard alkylating agent) for the treatment of patients with previously untreated chronic lymphocytic leukemia (CLL). CLL is the most common type of Leukaemia accounting for 35% of all reported Leukaemias (See CRUK CLL page). In a randomized three-arm clinical study, the combination of obinutuzumab (in combination with chlorambucil) improved the progression-free survival (PFS) of patients to 23.0 months compared to 11.1 months for chlorambucil alone. Obinutuzumab ( CHEMBL1743048 ) is a humanized anti-CD20 monoclonal antibody of ca . 150 kDa molecular weight. Its target, the B-lymphicyte antigen CD20, is the product of the gene MS4A1 (Uniprot: P11836; ChEMBL: CHEMBL2058 ; canSAR target synopsis . The CD20 antigen is expressed on the surface of pre B- and mature B-lymphocytes. Obinutuzumab mediates B-ce...

ATC Code: V09AX04 On October 25 th , the FDA approved Flutemetamol F18 (Tradename: Vizamyl ; Research Code: [ 18 F]AH110690 ), a radioactive diagnostic agent, for intravenous (i.v.) use in Positron Emission Tomography (PET) imaging of the brain in adult patients with cognitive impairment , who are being evaluated for Alzheimer’s disease (AD) and dementia. Alzheimer's disease is a non-treatable, progressively worsening and fatal disease, characterised by a decrease in cognitive functions, such as memory, and is usually associated with an accumulation of β amyloid (Uniprot: P05067 ) plaques in several brain regions. These deposits are believed to be responsible for cellular damage and ultimately cell death. Flutemetamol F18 is the second approved diagnostic drug to estimate β-amyloid neuritic plaque density, after the approval of Florbetapir F18 in 2012. Like Florbetapir F18, Flutemetamol F18 binds to β amyloid plaques in the brain where the F-18 isotope produces...

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...

ATC code: V09IA09 On March 13th 2013, the FDA approved Technetium Tc 99m Tilmanocept (LymphoSeek TM ), a radioactive diagnostic agent indicated for lymphatic mapping with a hand-held gamma counter to assist in the localisation of lymph nodes draining a primary tumour site in patients with breast cancer or melanoma .  Melanoma is a malignant skin tumour, which, although rather uncommon, causes 75% of skin cancer related deaths.  Breast cancer accounts for almost 23% of all cancers in women and in 2008 caused 13.7% of cancer related deaths in women. Lymph nodes drain lymphatic fluid coming from tissues, if the tissues contain a tumour, the node will retain cancer cells coming from it. By removing and analysing the lymph node, precious informations can be obtained regarding the spread of the tumour. Technetium Tc 99m Tilmanocept (ChEMBL: CHEMBL2108726 ) acts by accumulating in lymphatic tissue and selectively binding to mannose binding receptor ( CD206 , ChEMBL: CHEMBL...

ATC code : L01XE13 Wikipedia : Afatinib On July 12th 2013 the FDA approved Gilotrif TM (USAN afatinib) for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) carrying EGFR exon 19 deletions or exon 21 (L858R) mutation. It is a covalent, irreversible inhibitor of EGFR, ERBB2 and ERBB3. Non small cell lung cancer (NCLS) ( CRUK NCLS ; PDQ NCLS ) accounts for 78% of lung cancer incidences in the UK and is typically resistant to chemotherapy. In clinical studies, afatinib increased the mean Progression Free Survival to 11.1 months from 6.9 months (compared to standard of care Pemetrexed/Cisplatin). Furthermore, response to treatment was observed in tumors harboring several EGFR mutant species although the duration of response varied from 6.9 months to 16.5 months depending on the mutation . Afatinib covalently binds to the kinase domains of EGFR (ErbB1, Uniprot: P00533 ; canSAR: EGFR ”), HER2 (ErbB2, Uniprot: P04626 ;...