The ChEMBL-og

ATC Code (s): A08A , A10X , A16A Wikipedia: Metreleptin On February 24 th  2014, the FDA approved metreleptin (Tradename: Myalept ), a leptin analogue, as an adjunct to diet and replacement therapy, for the treatment of complications associated with leptin deficiency in patients with congenital or acquired generalized lipodystrophy . Lipodystrophy is a rare condition characterized by abnormalities in adipose (fat) tissue distribution. It can be congenital, i.e. the patient is born with little or no adipose tissue, or it can be acquired, for example, after prolonged antiretroviral drug therapy some patients keep on losing adipose tissue with time. The deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in non-adipose tissues such as liver and muscle, contributing to metabolic abnormalities including insulin resistance . Leptin is an endogenous hormone, predominantly secreted in the adipose tissue, responsible to signal to the ...

ATC Code: A10BX (incomplete) Wikipedia:   Canagliflozin ChEMBL:  CHEMBL2048484 On March 29th the FDA approved Canagliflozin (trade name  INVOKANA ™) to improve glycemic control for the treatment of diabetes type 2. Canagliflozin is to be used in combination with proper diet and exercise. Canagliflozin is a subtype 2 sodium-glucose transport protein ( SGLT2 , ChEMBL3884 ) inhibitor. Canagliflozin is a first-in-class drug with several others still in clinical trials .  Target SGLT2 is found in the proximal tubule of the nephron in the kidneys (as is paralog  SGLT1 , ChEMBL4979 ). SGLT2 one of the 5 known members of the sodium-glucose transporter proteins family. The transporter is responsible for 90 % of the total renal glucose reuptake  (corresponding to 98 % of the uptake in the proximal convoluted tubule). The protein has a relatively low affinity for glucose compared to SGLT1 ( 2 mM versus 0.4 mM...

ATC Code: C10AX11 Wikipedia: Mipomersen On January 29 st , the FDA approved Mipomersen (Tradename: Kynamro ; Research Code: ISIS-310312), an oligonucleotide inhibitor of apolipoprotein B-100 (apo B-100) synthesis, indicated as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C) , apolipoprotein B (apo B), total cholesterol (TC) , and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH) . Familial hypercholesterolemia is a genetic disorder, characterised by high levels of cholesterol rich low-density lipoproteins (LDL-C) in the blood. This genetic condition is generally attributed to a faulty mutation in the LDL receptor (LDLR) gene, which mediates the endocytosis of LDL-C. Mipomersen is the first antisense oligonucleotide that targets messenger RNA (mRNA) enconding apolipoprotein B-100 (Apo B-100), the principal apolipoprotein of LDL and its metabolic pre...

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: G04BD (incomplete) Wikipedia: Mirabegron On June 28 2012, the FDA approved Mirabegron (tradename: Myrbetriq ; Research Code: YM-178), a novel, first-in-class selective β3-adrenergic receptor  agonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. OAB syndrome is a urological condiction defined as urinary urgency, usually accompanied by frequency and nocturia , with or without urge urinary incontinence, in the absence of urinary tract infection or other obvious pathology. Mirabegron acts by relaxing the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of β3-receptor which in turn increases bladder capacity. Other treatments for OAB are already in the market and these include treatments with antimuscarinic drugs , such as Flavoxate (approved in 1970; tradename: Urispas; ChEMBL: CHEMBL1493 ), Oxybutynin (approved in 1975, tra...

    ATC code R07AX02  Wikipedia Ivacaftor On January 31st, FDA approved Ivacaftor (previously known as VX-770, trade name Kalydeco ) as a first-in-class oral drug for the treatment of a rare form of Cystic Fibrosis in patients aged 6 or older, caused by a G551D mutation of the CFTR gene. Cystic Fibrosis (OMIM 219700 ) is an autosomal recessive genetic disease caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, resulting in a defective CFTR protein, an ABC-class chloride-ion transporter in epithelial cell membranes. Cystic Fibrosis (CF) most typically affects the lungs, leading to the secretion of thick mucus, consequent breathing difficulties and eventual secondary bacterial airway infections in an age-dependent manner, i.e. early infections with Staphylococcus aureus which eventually are replaced by Pseudomonas aeruginosa as disease progresses. Traditionally, management of the symptoms involves mechanical removal o...

Wikipedia : Vismodegib On Jan 31st 2012 the FDA approved Vismodegib (tradename:  Erivedge TM , previously known as GDC-0449 and HhAntag691) a hedgehog signalling pathway inhibitor for the treatment metastatic basal cell carcinoma . This is a novel first-in-class medicine, which for the first time modulates the hedgehog pathway. The target of Vismodegib is smoothened  (SMO) (UniProt: Q99835 , CanSAR: link ). SMO is a class F (or class 6) G-Protein Coupled Receptor ( GPCR ) also known as the Frizzled/Smoothened class (pfam: PF01534 ). Smoothened is distinct and different to the previously 'drugged' GPCRs (which primarily target class A/class 1 receptors). The 3D-structures of smoothened or any of its homologues have not been characterised and are believed to differ from Class 1 GPCRs. Vismodegib (Chembl:  CHEMBL473417 , ChemSpider: 23337846 PubChem: CID24776445 , IUPAC: 2-chloro-N-[4-chloro-3-(pyridin-2-yl)phenyl]-4-(methylsulfonyl)benzamide)...