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Gefitinib (INN, /ɡɛˈfɪtɨnɪb/, trade name Iressa, marketed by AstraZeneca and Teva), is a drug used for certain breast, lung and other cancers. Gefitinib is an EGFR inhibitor, like erlotinib, which interrupts signaling through the epidermal growth factor receptor (EGFR) in target cells. Therefore, it is only effective in cancers with mutated and overactive EGFR.
Gefitinib is the first selective inhibitor of epidermal growth factor receptor's (EGFR) tyrosine kinase domain. Thus gefitinib is an EGFR inhibitor. The target protein (EGFR) is a family of receptors which includes Her1(erb-B1), Her2(erb-B2), and Her 3(erb-B3). EGFR is overexpressed in the cells of certain types of human carcinomas - for example in lung and breast cancers. This leads to inappropriate activation of the anti-apoptotic Ras signalling cascade, eventually leading to uncontrolled cell proliferation. Research on gefitinib-sensitive non-small cell lung cancers has shown that a mutation in the EGFR tyrosine kinase domain is responsible for activating anti-apoptotic pathways. These mutations tend to confer increased sensitivity to tyrosine kinase inhibitors such as gefitinib and erlotinib. Of the types of non-small
Iloperidone, also known as Fanapt, Fanapta, and previously known as Zomaril, is an atypical antipsychotic for the treatment of schizophrenia. It was approved by the U.S. Food and Drug Administration (FDA) for use in the United States on May 6, 2009.
Iloperidone is a monoamine directed towards acting upon and antagonizing specific neurotransmitters, particularly multiple dopamine and serotonin receptor subtypes. It is considered an ‘atypical’ antipsychotic because it displays serotonin receptor antagonism, similar to other atypical antipsychotics. The older typical antipsychotics are primarily dopamine antagonists.
Iloperidone has been shown to act as an antagonist at all tested receptors. It was found to block the sites of noradrenaline (α2C), dopamine (D2A and D3), and serotonin (5-HT1A and 5-HT6) receptors. In addition, pharmacogenomic studies identified single nucleotide polymorphisms associated with an enhanced response to iloperidone during acute treatment of schizophrenia.
Iloperidone performed well against a prepulse inhibition (PPI) experiment, which was designed to gauge the extent of sensory gating in rats, a process disrupted in schizophrenia. Prepulse inhibition is the
Lacosamide (INN, formerly known as erlosamide) is a medication developed by UCB for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain marketed under the trade name Vimpat.
The U.S. Food and Drug Administration accepted UCB's New Drug Application for lacosamide as of November 29, 2007, beginning the approval process for the drug. UCB also filed for marketing approval in the European Union; the European Medicines Agency accepted the marketing application for review in May 2007.
The drug was approved in the EU on September 3, 2008. It was approved in the US on October 29, 2008. Lacosamide release was delayed owing to an objection about its placement into schedule V of the Controlled Substances Act. The FDA issued their final rule of placement into Schedule V on June 22, 2009.
Lacosamide is a functionalized amino acid that has activity in the maximal electroshock seizure test, like antiepileptic drugs that are believed to act through voltage-gated sodium channels. However, lacosamide does not act in a conventional way to stabilize fast sodium channel inactivation. Rather, recent studies indicate that it enhances slow inactivation . During an action
Everolimus (RAD-001) is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an inhibitor of mammalian target of rapamycin (mTOR).
It is currently used as an immunosuppressant to prevent rejection of organ transplants and treatment of renal cell cancer and other tumours. Much research has also been conducted on everolimus and other mTOR inhibitors for use in a number of cancers.
It is marketed by Novartis under the tradenames Zortress (USA) and Certican (Europe and other countries) in transplantation medicine, and Afinitor in oncology.
Everolimus is approved for various conditions:
As of October 2010, Phase III trials are under way in gastric cancer, hepatocellular carcinoma and lymphoma. The use of everolimus in refractory chronic Graft-versus-host disease has been reported in 2012.
Interim phase III trial results in 2011 showed that adding Afinitor (everolimus) to exemestane therapy against advanced breast cancer can significantly improve progression-free survival compared with exemestane therapy alone.
In a similar fashion to other mTOR inhibitors its effect is solely on the mTORC1 protein and not on the mTORC2 protein. This can lead to a
Sunitinib (marketed as Sutent by Pfizer, and previously known as SU11248) is an oral, small-molecule, multi-targeted receptor tyrosine kinase (RTK) inhibitor that was approved by the FDA for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST) on January 26, 2006. Sunitinib was the first cancer drug simultaneously approved for two different indications.
Sunitinib inhibits cellular signaling by targeting multiple receptor tyrosine kinases (RTKs).
These include all receptors for platelet-derived growth factor (PDGF-Rs) and vascular endothelial growth factor receptors (VEGFRs), which play a role in both tumor angiogenesis and tumor cell proliferation. The simultaneous inhibition of these targets therefore leads to both reduced tumor vascularization and cancer cell death, and ultimately tumor shrinkage.
Sunitinib also inhibits KIT (CD117), the RTK that (when improperly activated by mutation) drives the majority of gastrointestinal stromal cell tumors. It has been recommended as a second-line therapy for patients whose tumors develop mutations in KIT that make them resistant to imatinib, or who become intolerant to the drug.
Milnacipran (Ixel, Savella, Dalcipran, Toledomin) is a serotonin–norepinephrine reuptake inhibitor (SNRI) used in the clinical treatment of fibromyalgia. It is not approved for the clinical treatment of major depressive disorder in the USA, but it is in other countries.
Milnacipran was first approved for the treatment of major depressive episodes in France in December 1996. It is currently marketed (as Ixel) for this indication in over 45 countries worldwide including several European countries such as Austria, Bulgaria, Finland, France, Portugal, and Russia. It is also available in Japan (as Toledomin) and Mexico (as Dalcipran). Cypress Bioscience bought the exclusive rights for approval and marketing of the drug for any purpose in the United States and Canada in 2003 from the manufacturer Laboratoires Pierre Fabre.
In January 2009 the U.S. Food and Drug Administration (FDA) approved milnacipran (under the brand name Savella) only for the treatment of fibromyalgia, making it the third medication approved for this purpose in the United States.
Milnacipran inhibits the reuptake of serotonin and norepinephrine in an approximately 1:3 ratio, respectively; in practical use this means a
Dasatinib, previously known as BMS-354825, is a cancer drug produced by Bristol-Myers Squibb and sold under the trade name Sprycel. Dasatinib is an oral multi- BCR/ABL and Src family tyrosine kinase inhibitor approved for use in patients with chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). It is being evaluated for use in numerous other cancers, including advanced prostate cancer.
The drug is named after one of the inventor chemists, Jagabandhu Das, who was a member of the large discovery and development team at Bristol Myers Squibb.
In a Phase I dose escalation study published in June 2006, dasatinib was tested in patients who were resistant to or who could not tolerate imatinib. Complete hematological responses were seen in 37 of 40 patients with chronic-phase CML. Major hematologic responses were seen in 31 of 44 patients with accelerated-phase CML, CML in blast crisis, or Ph+ ALL.
The main targets of dasatinib, are BCR/ABL, Src, c-Kit, ephrin receptors, and several other tyrosine kinases, but not erbB kinases such as EGFR or Her2.
Responses were maintained in 95% of patients with
Silodosin (trade names Rapaflo (USA), Silodyx (Europe), Rapilif (India), Silodal (India), Urief (Japan)) is a medication for the symptomatic treatment of benign prostatic hyperplasia. It acts as an α1-adrenoceptor antagonist with high uroselectivity (selectivity for the prostate).
Silodosin received its first marketing approval in Japan in May 2006 under the tradename Urief, which is jointly marketed by Kissei Pharmaceutical Co., Ltd. and Daiichi Sankyo Pharmaceutical Co., Ltd.
Kissei licensed the US, Canadian, and Mexican rights for silodosin to Watson Pharmaceuticals, Inc. in 2004.
On February 12, 2008, Watson announced that the New Drug Application submitted to the United States Food and Drug Administration for silodosin has been accepted for filing. FDA approved this drug on October 9th, 2008. Silodosin is marketed under the trade names Rapaflo in the US and Silodyx in Europe. and Rapilif in India (Ipca Urosciences)
Since silodosin has high affinity for the α1A adrenergic receptor, it causes practically no orthostatic hypotension (in contrast to other α1 blockers). On the other side, the high selectivity seems to cause more problems with ejaculation.
As α1A adrenoceptor