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...

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: not yet assigned Wikipedia: Crofelemer On December 31 2012, the FDA approved Crofelemer for the treatment of diarrhea caused by antiretroviral medication regimens taken by patients with HIV/AIDS . Diarrhea is a frequent adverse effect of antiretroviral medication - however, it can also be caused by secondary infections of the gastrointestinal tract or the virus itself. The loss of fluids incurred by diarrhea can lead to dehydration and electrolyte imbalance. As a side-effect of antiretroviral medication it also reduces patient compliance with a prescribed medication regimen. Crofelemer alleviates the symptoms of HIV-associated diarrhea by limiting the amount of chloride ions that are pumped into the intestinal lumen, thus also retaining sodium ions and water. Crofelemer is a natural product oligomer that is not orally bioavailable but acts locally on the intestinal surface. It was shown to inhibit two distinct intestinal chloride channels expressed in...

ATC code:  L01XX40 Wikipedia: Omacetaxine_mepesuccinate On October 22nd 2012 the FDA approved omacetaxine mepesuccinate (research code: CGX-635, trivial name: Homoharringtonine, trademark: Synribo TM ) for the treatment of chronic or accelerated phase chronic myeloid leukaemia ( CML ) in adults with resistance to two or more tyrosine kinase inhibitors. Omacetaxine is an old drug identified 35 years ago and known to have activity in CML, but its clinical development was previously halted due to the discovery of BCL-ABL and other targeted kinase inhibitors Pubmed: 21294709 . The rapid development of tyrosine kinase inhibitor resistant tumors has led to the need for agents that can act in these treatment-derived drug-resistant patients. Omacetaxine mepesuccinate has been approved based on observed major cytogenetic response rather than on improvement in disease-related symptoms or increased survival. Omacetaxine mepesuccinate/homoharr...

ATC code S01EE05 Wikipedia Tafluprost On Feb 13th, 2012 FDA approved Tafluprost ( trade name Zioptan) for treatment of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Tafluprost had been already available under the trade name Taflotan in Germany and Denmark from 2008, and under the trade name Saflutan in the United Kingdom and Spain from 2009. Glaucoma is an eye disease associated with increased fluid pressure in the eye, eventually causing permament damage to the optic nerve, impairing the field of vision and ultimately leading to blindness. Glaucomas can be sub-classified as open-angle glaucoma (OAG) and closed-angle glaucoma (CAG), with OAG being a slowly progressive disease responsible for ~90% of glaucoma cases in the US, and CAG being an acute disease with rapid progression. Alongside various surgical forms of treatment, management of OAG usually consists of medication to lower intraocular pressure. Taf...

On Jan 23rd 2012 the FDA approved Ingenol mebutate gel for the topical treatment of actinic keratosis (AK). Ingenol mebutate (trade name: PICATO ®, formally known as PEP-005) is a natural product derived from the euphorbia plant. Actinic, or solar keratosis ( Wikipedia ; NIH ; OMIM ) is a pre-cancerous pigmented lesion on the skin, most commonly occurring in skin that has been frequently exposed to the sun. If left untreated, about 20% of cases transform into Squamous Cell Carcinoma . Ingenol mebutate induces cell death in Actinic Keratosis. The precise targets responsible for the mechanism of action is not known, however, Ingenol derivatives (see e.g. CHEMBL346507 ) have been shown to have anticancer activities. Many of these derivatives have activity on several Protein Kinase C isoforms. Mechanistically Ingenol mebutate causes rapid lesion necrosis and also specific neutrophil-mediated, antibody-dependent cellular cytotoxicity Ingenol mebutate (IUPAC: 2-Butenoic acid, ...

ATC code (partial): A07A On May 27th 2011, the FDA approved Fidaxomicin (Tradename: Dificid ; Research Code: PAR-101, OPT-80, NDA 201699), a macrolide narrow spectrum antibacterial drug indicated for the treatment of Clostridium difficile -associated diarrhea (CDAD) in adults. Clostridium difficile ( C. difficile ) is an anaerobic, spore-forming Gram-positive bacteria , and overgrowth of this species can cause severe diarrhea and other more serious intestinal conditions, such as colitis . Fidaxomicin is a fermentation product obtained from the Actinomycete Dactylosporangium aurantiacum . It exerts its therapeutic effect by inhibiting beta subunit of the bacterial enzyme DNA-directed RNA polymerase (RNAP) (UniProt: Q890N5 ), resulting in the death of C. diffi cile . Bacterial RNA polymerase is a large (~400 kDa) five subunit protein, and is the target of the already approved antibiotic rifampicin . Other treatments for CDAD already in the market include anti...

ATC code (partial): G03   On 28th April 2011, the FDA approved Abiraterone acetate (Brand name Zytiga TM , NDA 202379) for the treatment of castrate-resistant prostate cancer (CRPC). Specifically, it is indicated for use in combination with prednisone for the treatment of patients with metastatic CRPC who have received prior chemotherapy containing docetaxel. Response biomarkers are amplified Androgen Receptor (AR); PTEN loss and hormone driven ERG rearrangement. Abiraterone acetate (research code: CB-7630) is a steroid derivative with a chemical formula C26H33NO, (IUPAC: (3β)­ 17-(3-pyridinyl)androsta-5,16-dien-3-yl acetate; SMILES= (CC(=O)O[C@H]1CC[C@]2(C)[C@H]3CC[C@@]4(C)[C@@H](CC=C4c5cccnc5)[C@@H]3CC=C2C1 ); InChI=1S/C26H33NO2/c1-17(28)29-20-10-12-25(2)19(15-20)6-7-21-23-9-8-22(18-5-4-14-27-16-18)26(23,3)13-11-24(21)25/h4-6,8,14,16,20-21,23-24H,7,9-13,15H2,1-3H3/t20-,21-,23-,24-,25-,26+/m0/s1). It has molecular weight 391.55 and a LogP of 5.12. Abiraterone ...

ATC code : V09AB03 On January 14 th 2011, the FDA approved Ioflupane 123 I (USAN:  Ioflupane I123 USAN date: 2009 tradename: DaTSCAN , NDA 022454)) for the imaging of dopamine transporters in the brain of adult patients with potential Parkinsonian Syndromes . Ioflupane is a radiopharmaceutical agent intended for use with single photon emission computed tomography ( SPECT ) imaging, to help physicians differentiate essential tremor , from tremor due to Parkinsonian Syndromes. Ioflupane 123 I binds to, and allows imaging of, the Dopamine Transporter (DaT) (K i = 0.62 nM IC 50 = 0.71 nM). Synonym: SLC6A3 UniProt: Q01959 Pfam: PF00209 ). Variation or malfunction of the Dopamine Transporter is linked to many neurological and psychiatric disorders. The chemical structure of Ioflupane (IUPAC: methyl(1S,3S,4S,5R)-8-(3-fluoropropyl)-3-(4-iodanylphenyl)-8-azabicyclo[3.2.1]octane-4-carboxylate PubChem: CID3086674 ) is a tropane derivative; tropanes are a ...

partial ATC code : P03A The first FDA new drug approval of 2011 is Spinosad, approved on Jan 18th 2011 (NDA 022408). Spinosad (tradename: Natroba ) is a pediculicide , indicated for the topical treatment of head lice (the parasitic insect Pediculus humanus capitis) infestations in patients aged over four years of. One gram of Natroba contains 9 mg of Spinosad as a viscous suspension. Spinosad has a unique mode of action that is different from all other known pediculicides. Spinosad causes excitation of the insect nervous system, leading to involuntary muscle contractions, prostration tremors and finally paralysis and death. These effects are similar to those associated with the activation of nicotinic acetylcholine receptors (nAChRs) , and there is evidence that insect nAChRs are involved in the mechanism of action of spinosyn A and D (two active components of Spinosad) a representative nAChR for a target species is Drosophila melanogaster nAChR Dalpha6 (UniProt: Q86M...