The ChEMBL-og

ATC code : G03AB08 and G03FA15 (as combinations) On May 6th 2010, the FDA approved Dienogest, as a component of the oral contraceptive drug Natazia (tradename: Natazia , tradename: Qlaira ). Dienogest (research code:STS-557) is a progestin is a synthetic analog of the natural product progesterone . Dienogest is one of two active components within Natazia, the other being the 17ß-estradiol prodrug - estrogen valerate; Natazia is therefore a Combination Oral Contraceptive (or COC ). Natazia is the first four-phase combined oral contraceptive marketed in the United States - the four phases refering to the differential dosing of the estrogen/progestin throughout the menstrual cycle . Each monthly pack of Natazia contains pills to be taken in a specific order: 2 dark yellow tablets each containing 3 mg estradiol valerate; then 5 medium red tablets each containing 2 mg estradiol valerate and 2 mg dienogest; then 17 light yellow tablets each containing 2 mg estradiol valerate and...

Here is an initial list of the 2010 US new approved drugs (specifically New Molecular Entities). The way we count things, there were 19 novel newly approved drug substantces in the US last year. # USAN Tradename Icon 1 Tocilizumab Actemra / RoActemra 2 Dalfampridine Ampyra 3 Liraglutide Victoza 4 Velaglucerase alfa VPRIV 5 Carglumic acid Carbaglu 6 Polidocanol Asclera 7 Denosumab Prolia 8 Cabazitaxel Jevtana 9 Sipuleucel-T Provenge 10 Ulipristal Acetate Ella 11 Alcafatadine Lastacaft 12 Pegloticase Krystexxa 13 Fingolimod Gilenya 14 Dabigatran Etexilate Pradaxa 15 Lurasidone Latuda 16 Ceftaroline Fosamil Teflaro 17 Eribulin Mesylate Halaven 18 Tesamorelin Egrifta 19 Dienogest Natazia 12 are small molecule drugs, and 7 are biologicals. Of the small molecule drugs, 6 (32%) are small molecule synthetic drugs , 6 (32%) are small molecule natural product-derived drugs , 6 (32%) are biologicals (including pepti...

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 (partial): L01C On November 15th, 2010, the FDA approved Eribulin Mesylate (ResearchCode:E-7389) under the trade name Halaven (TradeMark: Halaven ). It is indicated for for the treatment of patients with late stage, metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. Phase III trials showed that patients survived a median of 2.5 months longer than patients treated with other current alternatives. Eribuln is a synthethic analogue of halichondrin B , a cytotoxic polyether macrolide marine natural product. The mechanism of action of Eribulin is anti-mitotic and is mediated via tubulin binding, where it leads to G2/M block in the the cell-cycle ; after prolonged stalling in this state, cells enter apoptosis and are then cleared. Eribulin is a large (Mwt 729.9 for Eribulin and 826.0 for the mesylate salt) synthetic compound (an analogue of halichondrin B) an IUPAC name of the s...

ATC code (partial): J01DI On October 29th, FDA has approved Ceftaroline Fosamil under the trade name Teflaro. Ceftaroline Fosamil (previously known by the research code TAK-599, the parent drug, Ceftaroline is also known as T-91,825) is an antibiotic indicated for the treatment of adults with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible Gram-positive and Gram-negative microorganisms, such as Staphylococcus aureus (including methicillin-susceptible and -resistant isolates), Streptococcus pyogenes , Streptococcus agalactiae , Escherichia coli , Klebsiella pneumoniae , and Klebsiella oxytoca , and also for the treatment of community-acquired bacterial pneumonia (CABP) caused by susceptible Gram-positive and Gram-negative bacteria, such as Streptococcus pneumoniae (including cases with concurrent bacteremia ), Staphylococcus aureus (methicillin-susceptible isolates only), Haemophilus influenzae , Klebsiella pneumoniae , Klebsiella oxytoca , an...

ATC code (partial): N05AE On October 28th 2010, the FDA approved Lurasidone (Tradename:Latuda) (Lurasidone is also known by the research code SM-13,496). Lurasidone is an atypical antipsychotic agent indicated for the treatment schizophrenia. Lurasidone displays broad polypharmacology against a wide range of rhodopsin-like aminergic GPCRs, acting as an antagonist with high affinity at dopamine D2 receptors (Uniprot: P14416 , ChEMBL: 72 ) (Ki of 1 nM), serotonin 5-HT2A (Uniprot: P28223 , ChEMBL: 107 ) (Ki of 0.47 nM) and 5-HT7 receptors (Uniprot: P34969 , ChEMBL: 10209 ) (Ki of 0.49 nM), and with moderate affinity at alpha-2C adrenergic receptors (Uniprot: P18825 , ChEMBL: 218 ) (Ki of 10.8 nM) and at alpha-2A adrenergic receptors (Uniprot: P08913 , ChEMBL: 52 ) (Ki of 40.7 nM). Lurasidone acts also as a partial agonist at serotonin 5-HT1A receptors (Uniprot: P08908 , ChEMBL: 51 ) (Ki of 6.4 nM) and exhibits little or no affinity for histamine H1 (Uniprot: P35367 , ChEMBL: 127 ) ...

ATC Code: B01AE07 Dabigatran etexilate has been approved by the FDA on October 19th 2010. Dabigatran etexilate (also known as BIBR-1048 for Dabigatran etexilate and BIBR-953 for Dabigatran) is approved for the treatment of patients with atrial fibrillation at risk of embolism or stroke. Dabigatran etexilate is a first-in-class (for the US) oral drug preventing blood clotting and stroke by direct inhibition of thrombin and is marketed under the trade name Pradaxa in Europe and the US, and Pradax in certain other territories. In Europe, an earlier oral direct thrombin inhibitor Xemelagatran  (trademark:Exanta trademark:Exarta also known as H376/95) was approved, but subsequently was withdrawn due to commercial and perceived safety issues. The formation of blood clots in the circulation can cause embolism or stroke (or CVA) if other risk factors are present.  Depending on the number of risk factors, the risk of suffering a stroke increases up to 7-fold in patients with atr...

ATCC:  M04AX02 On September 14th 2010, the FDA approved Pegloticase under the trade name Krystexxa. Pegloticase is a recombinant enzyme for the treatment of gout and can replace xanthine oxidase (XO) inhibitors for patients who do not respond to or cannot tolerate treatment with xanthine oxidase inhibitors.  Gout is a painful affliction caused by microscopic needle-shaped crystals of sodium urate which precipitate in joints and tendons and stimulate a local inflammatory response. These attacks of inflammatory arthritis not only cause pain and stiffness of the joint, but, if left untreated for years, also damage the cartilage and surrounding tissue. Hard, non-painful deposits of crystalline uric acid known as tophi occur in the joints and sometimes the kidney.  Gout is generally associated with obesity, hypertension, insulin resistance and hyperlipidaemia. In more than half of the cases of diagnosed gout, patients have elevated blood levels of uric acid. Conve...

ATC code: L04AA27 On September 21st, the FDA approved Fingolimod (previously known as FTY-720) for the treatment of relapsing forms of multiple sclerosis ( MS ). Fingolimod is marketed under the name Gilenya and is the first oral drug that can slow the progression of MS. MS is a chronic autoimmune disorder affecting the central nervous system (CNS) and causing a broad spectrum of neurological symptoms ranging from numbness of the limbs and muscle weakness to cognitive impairment, depression, and a broad spectrum of other disorders. People suffering from MS experience inflammatory reactions which damage the myelin sheath surrounding the axons of nerve cells. The inflicted lesions impair the transmission of action potentials and ultimately perturb normal function of the CNS. Upon administration, Fingolimod is phosphorylated by sphingosine kinase (Uniprot: Q9NRA0 ) to form the the active metabolite Fingolimod-phosphate - Fingolimod is therefore a prodrug . Fingolimod-phosphate bi...

ATC code:  The summer got in the way of a timely post on this new drug. On 28 July 2010, Alcaftadine was approved for the treatment of patients with allergic conjunctivitis as a 0.25% opthalmic solution. This allergic reaction is most familiar in patients with hay fever but can also be caused by other allergens such as dust mites, moulds, perfumes etc . It causes red, itchy and watery eyes. Allergic conjunctivitis is caused by a type I hypersensitivity reaction of the immune system. Antigenic epitopes of the allergen are detected by IgE antibodies which mediate the excessive activation of mast cells and basophils .  The symptoms of allergic conjunctivitis are mainly caused by the release of histamine from these activated immune cells. Histamine increases the permeability of blood vessels and stimulates the activity of immune cells, through a number of differing histamine receptors. Alcaftadine and it's carboxylic acid metabolite (produced via a non P450 route) are...

ATC code: G03AD02 The most recent approval by FDA is Ulipristal Acetate, approved on August 13th 2010 under the trade name Ella. Ulipristal Acetate (previously known by the research code CDB-2914 or VA-2914) is a progesterone agonist/antagonist emergency contraceptive, indicated for prevention of pregnancy following unprotected intercourse or known or suspected contraceptive failure. This drug is a selective progesterone receptor modulator (SPRM) with antagonist and partial agonist effects (a progesterone agonist/antagonist) at the progesterone receptor (PR, NR3C3) (Uniprot code: P06401 ). The Progesterone Receptor is a member of a very significant family of proteins for drug discovery, the Nuclear Receptors , a family of around 50 genes which are transcription factors , the transcription by NRs is usually ligand regulated. Ulipristal Acetate prevents progesterone, the endogenous ligand, from occupying its receptor. Ulpristal Acetate binds in the ligand binding domain (LBD) of PR ...