The ChEMBL-og

Wikipedia : Albiglutide ChEMBL :  CHEMBL2107841 On April 15th the FDA approved Tanzeum (albiglutide) subcutaneous injection to improve glycemic control, along with diet and exercise, in adults with type 2 diabetes. Type II diabetes Type II diabetes is a metabolic disorder that is characterized by high blood sugar (hyperglycemia) due to insulin resistance or relative lack of insulin. The disease affects millions of patient world-wide and can lead to long-term complications if the blood levels are not lowered in the patients: heart diseases, strokes and kidney failure. Albiglutide The drug is a dipeptidyl peptidase-4-resistant glucagon-like peptide-1 dimer fused to human albumin. Schematic representation of the albiglutide ( EMA ) Mode of action Traditionally, a decrease in the glucose blood level of affected patients is triggered using insulin injections. One alternative mechanism consists at indirectly stimulating insulin release us...

ATC code:  A16AX08 Wikipedia: Teduglutide On December 27, FDA approved Teduglutide (Tradename: Gattex®, Tradename: Revestive, Research Code: ALX-600, CAS# 197922-42-2), an analog of Glucagon-like peptide 2 ( GLP2 ) expressed in  Escherichia coli by recombinant DNA ( rDNA ) technology indicated for the treatment of adult patients with Short Bowel Syndrome ( SBS ). Short Bowel Syndrome (MeSH:  D012778 ) is a condition in which nutrients are not properly absorbed ( malabsorption disorder) caused by surgical removal of small intestine, or rarely due to the complete dysfunction of large segment of bowel. More information about SBS can be found in Medscape . Teduglutide is an analog of naturally occurring Glucagon-like peptide 2 (GLP2), which is 33 amino acid peptide created by specific post-translational proteolytic cleavage of proglucagon in endocrine L cells of the distal intestine. GLP2 is known to increase intestinal an...

ATC code: H01CB05 Wikipedia: Pasreotide On December 14, the FDA approved Pasireotide diaspartate (SIGNIFOR®, Research CodeL SOM-230, CAS#  396091-73-9 , Pub-Chem :  CID 9941444 , KEGG :  D10147 ), a cyclohexide with pharmacologic properties mimicking those of natural hormone Somatostatin for treatment of adult patients with Cushing's disease  (CD) for whom pituitary surgery is not an option or has not been curative. Cushing's disease (CD) is a cause of Cushing's syndrome characterised by increased secretion of ACTH (adrenocorticotropic hormone) from the anterior pituitary. CD is a rare hormone disorder, and  recent statistics indicate that the annual incidence is somewhere between 1 and 10 per million and is 3 times more common in women than in men (from NEMDIS ). This is most often as a result of pituitary adenoma  or due to excess production of hypothalamus Corticotropin releasing hormone ( CRH ). More information can be found i...

ATC Code: A03A (incomplete) Wikipedia: Linaclotide On Agust 30, the FDA approved Linaclotide (tradename: Linzess ; Research Code: MD-1100, ASP-0456), a novel, first-in-class Guanylate Cyclase-C (GC-C) agonist indicated for the treatment in adults of irritable bowel syndrome with constipation (IBS-C), and chronic idiophatic constipation (CIC) . CIC is a diagnosis given to people who experience persistent constipation and do not respond to standard treatment. IBS-C is a subtype characterized by chronic abnominal pain, discomfort, bloating and alteration of bowel habits. Linaclotide exherts its therapeutic action by binding to GC-C, resulting in an increase in both intracellular and extracellular concentrations of cyclic guanosine monophosphate (cGMP) . Increase in intracellular cGMP stimulates secretion of chloride and bicarbonate into the intestinal lumen, mainly through activation of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel, resulting ...

ATC Code: L01XX Wikipedia: Carfilzomib On July 20th 2012 the FDA approved Carfilzomib (Kyorolis TM ) for the treatment of patients with multiple myeloma who have received prior therapies including bortezomib and an immunomodulatory therapy, and who have demonstrated disease progression within 60 days of completion of the previous therapy. Multiple myeloma is a cancer of the Plasma Cells and usually in the bone marrow. Five year survival is about 40% in the UK and and the USA . Carfilzomib is a chirally defined modified tetrapeptidyl epoxide substrate analogue with a molecular weight of 719.9. The molecular formula is C40H57N5O7. (SMILES= O=C(N[C@H](C(=O)N[C@H](C(=O)N[C@H(C(=O)N[C@H](C(=O)[C@@]1(OC1)C)CC(C)C)Cc2ccccc2)CC(C)C)CCc3ccccc3)CN4CCOCC4) Cmax and AUC following a single intravenous dose of 27 mg/m2 was 4,232 ng/mL and 379 ng.hr/mL, respectively. The mean steady-state volume of distribution of a 20 mg/m2 dose of carfilzomib was 28 L. Carfilzomib was rapidly an...

ATC code : B03XA (incomplete) On March 27, the FDA approved Peginesatide for the treatment of anemia due to chronic kindney disease (CDK) in patients on dialysis. CDK is a slow but progressive loss of kidney function that can be caused by diabetes mellitus ,  hypertension and glomerulonephritis , among others. One of the symptoms in the advanced stages of CDK is anemia, a decrease in the number of red blood cells and hence the hemoglobin (adult hemoglobin: heterotetramer of two copies of  P69905 and two copies of  P68871 ) content of the blood. Anemia in patients suffering from CDK is caused by reduced production of erythropoetin , a hormone that regulates the levels of red blood cells and is synthesized predominantly in the cortex of the kidney. Anemia induced by CDK can be treated by supplying exogenous erythroepotin or analogs of this hormone ( e.g . Methoxy polyethylene glycol-epoetin beta, CHEMBL1201829 ). The collective term for these substances is eryt...

ATCC: C01EB19 Wikipedia: Icatibant On the August 25th 2011, the FDA approved Icatibant (trade name: Firazyr TM ), a bradykinin B2 receptor (B2R) antagonist indicated for the treatment of acute attacks of hereditary angioedema (HAE) in patients aged 18 or older. HAE is a rare genetic disease and is caused by low levels of C1-esterase inhibitor (C1-INH) , the major endogenous inhibitor and regulator of the protease plasma kallikrein and the key regulator of the Factor XII/kallikrein cascade. One component this cascade is the production of bradykinin by plasma kallikrein. During HAE attacks, disregulated activity of plasma kallikrein leads to excessive bradykinin production; bradykinin is a potent vasodilator, which s thought to be responsible for the characteristic HAE symptoms of localised swelling, inflammation and pain. Icatibant treats the clinical symptoms of HAE attack by selective- and competitively binding, as an antagonist, to the B2 bradykinin receptor (B2...

ATC code (partial): J On May 23 rd , the FDA approved Telaprevir (Tradename: Incivek ; Research Code: VX-950, NDA 201917), a Hepatitis C virus NS3 protease  (HCV NS3) inhibitor, for the treatment of chronic hepatitis C virus genotype 1  infection, in combination with peginterferon alfa and ribavirin . HCV is a prolonged infection that affects the liver and is caused by a small positive 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 if untreated, potentially fatal liver failure. There is currently no vaccine for this type of hepatitis. Telaprevir is an inhibitor of the hepatitis C virus (HCV) non-structural protein 3 (NS3) protease (ChEMBLID: CHEMBL4893 ; Uniprot ID: A3EZI9 ), a viral protein required for the proteolytic cleavage of the HCV encoded polyprotein (UniProt: P27958 ) into mature forms of the NS4A, NS4B, NS5A and NS5B proteins (NS3 is Unip...

ATC code (partial): J On May 13 th , the FDA approved Boceprevir (Tradename: Victrelis ; Research Code: SCH-503034, NDA202258), a Hepatitis C virus NS3 protease  (HCV NS3) inhibitor, for the treatment of chronic hepatitis C virus genotype 1  infection, in combination with peginterferon alfa and ribavirin . Chronic hepatitis C genotype 1 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. Boceprevir is a first-in-class inhibitor of the hepatitis C virus (HCV) non-structural protein 3 (NS3) protease (ChEMBLID: CHEMBL4893 ; Uniprot ID: A3EZI9 ), a viral protein required for the proteolytic cleavage of the HCV encoded polyprotein (UniProt: P27958 ) into mature forms of the NS4A, NS4B, NS5A and NS5B proteins (NS3 is Uniprot: P27958[1027-1657] ). These proteins ar...

ATC code (partial): H01AC Also this month, on November 10th, FDA has approved Tesamorelin under the trade name Egrifta. Tesamorelin (research code:TH-9507) is an analog of the human growth hormone-releasing factor (GRF)  (UniProt: P01286 , synonym:Somatoliberin, synonym:GRF, synonym:GHRH) indicated for the reduction of excess abdominal fat in HIV -infected patients with lipodystrophy . Lipodystrophy is a condition in which excess fat develops in atypical areas of the body, most notably around the liver, stomach, and other abdominal organs. This condition is observed as a side effect with many antiretroviral drugs used to treat HIV. Tesamorelin is the first-FDA approved treatment specifically approved for lipodystropy. The -relin INN stem covers prehormones or hormone releasing peptides, a very broad range of targets and pharmacology. The -morelin stem sub-group covers growth hormone-release stimulating peptides including capromorelin, dumorelin, examorelin, ipamorelin, pralm...

ATC code: A10BX07 Also approved in January is Liraglutide, on January 25th, under the trade name Victoza. Liraglutide, previously known as NN2211, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus . People with this type of diabetes are often overweight, have high blood pressure and/or cholesterol and become insensitive to insulin. Type 2 diabetes is the commonest form of diabetes, and is a major health problem in 'developed' economies. Liraglutide ATC code is A10BX07 .  Liraglutide works by activating the GLP-1 receptor (GLP-1R), which in turn stimulates the adenylyl cyclase pathway leading to insulin release in the presence of elevated glucose concentrations. GLP-1R is a class-II GPCR (also known as secretin receptor family). Liraglutide is the second GLP-1 agonist approved for the treatment of type 2 diabetes, after Exenatide (marketed as Byetta...