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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/06 15:36:13」(JST)
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| Systematic (IUPAC) name | |
|---|---|
| 4-[(4-methylpiperazin-1-yl)methyl]-N-(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide | |
| Clinical data | |
| Trade names | Gleevec, Glivec |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a606018 |
| Licence data | EMA:Link, US FDA:link |
| Pregnancy cat. | D (AU) D (US) |
| Legal status | POM (UK) ℞-only (US) |
| Routes | Oral |
| Pharmacokinetic data | |
| Bioavailability | 98% |
| Protein binding | 95% |
| Metabolism | Hepatic (mainly CYP3A4-mediated) |
| Half-life | 18 hours (imatinib) 40 hours (active metabolite) |
| Excretion | Fecal (68%) and renal (13%) |
| Identifiers | |
| CAS number | 152459-95-5 Y 220127-57-1 (mesilate) |
| ATC code | L01XE01 |
| PubChem | CID 5291 |
| DrugBank | DB00619 |
| ChemSpider | 5101 Y |
| UNII | BKJ8M8G5HI Y |
| KEGG | D08066 Y |
| ChEBI | CHEBI:45783 Y |
| ChEMBL | CHEMBL941 Y |
| Chemical data | |
| Formula | C29H31N7O |
| Mol. mass | 493.603 g/mol 589.7 g/mol (mesilate) |
|
SMILES
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InChI
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| Y (what is this?) (verify) |
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Imatinib (INN), marketed by Novartis as Gleevec (U.S.) or Glivec (Europe/Australia/Latin America), is a tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).[1] Like all tyrosine-kinase inhibitors, imatinib works by preventing a tyrosine kinase enzyme, in this case BCR-Abl, from phosphorylating subsequent proteins and initiating the signaling cascade necessary for cancer development, thus preventing the growth of cancer cells and leading to their death by apoptosis.[2] Because the BCR-Abl tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, imatinib works as a form of targeted therapy—only cancer cells are killed through the drug's action.[3] In this regard, imatinib was one of the first cancer therapies to show the potential for such targeted action, and is often cited as a paradigm for research in cancer therapeutics.[4]
Imatinib has been cited as the first of the gratuitously expensive cancer drugs, costing $92,000 a year. Doctors and patients complain that this is excessive, given that its development costs have been recovered many times over, and that the costs of synthesizing the drug are orders of magnitude lower. In the USA, the patent protecting the active principal will expire on 4 January 2015 while the patent protecting the beta crystal form of the active principal ingredient will expire on 23 May 2019.[5]
The developers of imatinib were awarded the Lasker Award in 2009 and the Japan Prize in 2012.[6][7]
Contents
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Medical uses [edit]
Imatinib is used in chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs) and a number of other malignancies. One study demonstrated that imatinib mesylate was effective in patients with systemic mastocytosis, including those who had the D816V mutation in c-Kit.[8] Experience has shown, however, that imatinib is much less effective in patients with this mutation, and patients with the mutation comprise nearly 90% of cases of mastocytosis.
Chronic myelogenous leukemia [edit]
The U.S. Food and Drug Administration (FDA) has approved imatinib as first-line treatment for Philadelphia chromosome (Ph)-positive CML, both in adults and children. The drug is approved in multiple Ph-positive cases CML, including after stem cell transplant, in blast crisis, and newly diagnosed.[9]
Gastrointestinal stromal tumors [edit]
The FDA first granted approval for advanced GIST patients in 2002. On 1 February 2012, imatinib was approved for use after the surgical removal of KIT-positive tumors to help prevent recurrence.[10] The drug is also approved in unresectable KIT-positive GISTs.[9]
Other [edit]
The FDA has approved imatinib for use in adult patients with relapsed or refractory Ph-positive ALL, myelodysplastic/ myeloproliferative diseases associated with platelet-derived growth factor receptor gene re-arrangements, aggressive systemic mastocytosis (ASM) without or an unknown D816V c-KIT mutation, hypereosinophilic syndrome (HES) and/or chronic eosinophilic leukemia (CEL) who have the FIP1L1-PDGFRα fusion kinase (CHIC2 allele deletion) or FIP1L1-PDGFRα fusion kinase negative or unknown, unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans.[9] On 25 January 2013, Gleevec was approved for use in children with Ph+ ALL.[11]
For treatment of progressive plexiform neurofibromas associated with neurofibromatosis type I, early research has shown potential for using the c-kit tyrosine kinase blocking properties of imatinib.[12][13][14][15][16]
Experimental [edit]
Imatinib may also have a role in the treatment of pulmonary hypertension. It has been shown to reduce both the smooth muscle hypertrophy and hyperplasia of the pulmonary vasculature in a variety of disease processes, including portopulmonary hypertension.[17] In systemic sclerosis, the drug has been tested for potential use in slowing down pulmonary fibrosis. In laboratory settings, imatinib is being used as an experimental agent to suppress platelet-derived growth factor (PDGF) by inhibiting its receptor (PDGF-Rβ). One of its effects is delaying atherosclerosis in mice without[18] or with diabetes.[19]
Mouse animal studies at Emory University in Atlanta have suggested that imatinib and related drugs may be useful in treating smallpox, should an outbreak ever occur.[20]
In vitro studies identified that a modified version of imatinib can bind to gamma-secretase activating protein (GSAP), which selectively increases the production and accumulation of neurotoxic beta-amyloid plaques. This suggests molecules that target at GSAP and are able to cross blood–brain barrier are potential therapeutic agents for treating Alzheimer's disease.[21] Another study suggests that imatinib may not need to cross the blood–brain barrier to be effective at treating Alzheimer's, as the research indicates the production of beta-amyloid may begin in the liver. Tests on mice indicate that imatinib is effective at reducing beta-amyloid in the brain.[22] It is not known whether reduction of beta-amyloid is a feasible way of treating Alzheimer's, as an anti-beta-amyloid vaccine has been shown to clear the brain of plaques without having any effect on Alzheimer symptoms.[23]
A formulation of imatinib with a cyclodextrin (Captisol) as a carrier to overcome the blood–brain barrier is also currently considered as an experimental drug for lowering and reversing opioid tolerance. Imatinib has shown reversal of tolerance in rats.[24] Imatinib is an experimental drug in the treatment of desmoid tumor or aggressive fibromatosis.
Adverse effects [edit]
bcr-abl kinase (green), which causes CML, inhibited by imatinib (red; small molecule).
The most common side effects include: feeling sick (nausea), diarrhoea, headaches, leg aches/cramps, fluid retention, visual disturbances, itchy rash, lowered resistance to infection, bruising or bleeding, loss of appetite;[25] weight gain, reduced number of blood cells (neutropenia, thrombocytopenia, anemia), and edema.[26]
Severe congestive cardiac failure is an uncommon but recognized side effect of imatinib and mice treated with large doses of imatinib show toxic damage to their myocardium.[27]
If imatinib is used in prepubescent children, it can delay normal growth, although a proportion will experience catch-up growth during puberty.[28]
Pharmacology [edit]
Pharmacokinetics [edit]
Imatinib is rapidly absorbed when given by mouth, and is highly bioavailable: 98% of an oral dose reaches the bloodstream. Metabolism of imatinib occurs in the liver and is mediated by several isozymes of the cytochrome P450 system, including CYP3A4 and, to a lesser extent, CYP1A2, CYP2D6, CYP2C9, and CYP2C19. The main metabolite, N-demethylated piperazine derivative, is also active. The major route of elimination is in the bile and feces; only a small portion of the drug is excreted in the urine. Most of imatinib is eliminated as metabolites, only 25% is eliminated unchanged. The half-lives of imatinib and its main metabolite are 18 and 40 hours, respectively. It blocks the activity of Abelson cytoplasmic tyrosine kinase (ABL), c-Kit and the platelet-derived growth factor receptor (PDGFR). As an inhibitor of PDGFR, imatinib mesylate appears to have utility in the treatment of a variety of dermatological diseases. Imatinib has been reported to be an effective treatment for FIP1L1-PDGFRalpha+ mast cell disease, hypereosinophilic syndrome, and dermatofibrosarcoma protuberans.[29]
Mechanism of action [edit]
Imatinib is a 2-phenyl amino pyrimidine derivative that functions as a specific inhibitor of a number of tyrosine kinase enzymes. It occupies the TK active site, leading to a decrease in activity.
There are a large number of TK enzymes in the body, including the insulin receptor. Imatinib is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor).
In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein of abl with bcr (breakpoint cluster region), termed bcr-abl. As this is now a constitutively active tyrosine kinase, imatinib is used to decrease bcr-abl activity.
The active sites of tyrosine kinases each have a binding site for ATP. The enzymatic activity catalyzed by a tyrosine kinase is the transfer of the terminal phosphate from ATP to tyrosine residues on its substrates, a process known as protein tyrosine phosphorylation. Imatinib works by binding close to the ATP binding site of bcr-abl, locking it in a closed or self-inhibited conformation, and therefore inhibiting the enzyme activity of the protein semi-competitively.[30] This fact explains why many BCR-ABL mutations can cause resistance to imatinib by shifting its equilibrium toward the open or active conformation.[31]
Imatinib is quite selective for bcr-abl – it does also inhibit other targets mentioned above (c-kit and PDGF-R), but no other known tyrosine kinases. Imatinib also inhibits the abl protein of non-cancer cells but cells normally have additional redundant tyrosine kinases which allow them to continue to function even if abl tyrosine kinase is inhibited. Some tumor cells, however, have a dependence on bcr-abl.[32] Inhibition of the bcr-abl tyrosine kinase also stimulates its entry in to the nucleus, where it is unable to perform any of its normal anti-apoptopic functions.[33]
The Bcr-Abl pathway has many downstream pathways including the Ras/MapK pathway, which leads to increased proliferation due to increased growth factor-independent cell growth. It also affects the Src/Pax/Fak/Rac pathway. This affects the cytoskeleton, which leads to increased cell motility and decreased adhesion. The PI/PI3K/AKT/BCL-2 pathway is also affected. BCL-2 is responsible for keeping the mitochondria stable; this suppresses cell death by apoptosis and increases survival. The last pathway that Bcr-Abl affects is the JAK/STAT pathway, which is responsible for proliferation.[34]
Interactions [edit]
Since imatinib is mainly metabolised via the liver enzyme CYP3A4, substances influencing the activity of this enzyme change the plasma concentration of the drug. An example of a drug that increases imatinib activity and therefore side effects by blocking CYP3A4 is ketoconazole. The same could be true of itraconazole, clarithromycin, grapefruit juice, among others. Conversely, CYP3A4 inductors like rifampicin and St. John's Wort reduce the drug's activity, risking therapy failure. Imatinib also acts as an inhibitor of CYP3A4, 2C9 and 2D6, increasing the plasma concentrations of a number of other drugs like simvastatin, ciclosporin, pimozide, warfarin, metoprolol, and possibly paracetamol. The drug also reduces plasma levels of levothyroxin via an unknown mechanism.[26]
As with other immunosuppressants, application of live vaccines is contraindicated because the microorganisms in the vaccine could multiply and infect the patient. Inactivated and toxoid vaccines do not hold this risk, but may not be effective under imatinib therapy.[35]
History [edit]
Imatinib was developed in the late 1990s by biochemist Nicholas Lydon, a former researcher for Novartis, and oncologist Brian Druker of Oregon Health & Science University (OHSU). Other major contributions to imatinib development were made by Carlo Gambacorti-Passerini, a physician scientist and hematologist at University of Milano Bicocca, Italy, John Goldman at Hammersmith Hospital in London, UK, and later on by Charles Sawyers of Memorial Sloan-Kettering Cancer Center.[36] Druker led the clinical trials confirming its efficacy in CML.[37]
Imatinib was developed by rational drug design. After the Philadelphia chromosome mutation and hyperactive bcr-abl protein were discovered, the investigators screened chemical libraries to find a drug that would inhibit that protein. With high-throughput screening, they identified 2-phenylaminopyrimidine. This lead compound was then tested and modified by the introduction of methyl and benzamide groups to give it enhanced binding properties, resulting in imatinib.[38]
Gleevec received FDA approval in May 2001. On the same month it made the cover of TIME magazine as the "magic bullet" to cure cancer. Druker, Lydon and Sawyers received the Lasker-DeBakey Clinical Medical Research Award in 2009 for "converting a fatal cancer into a manageable chronic condition".[36]
Gleevec also holds the record for the drug with the fastest approval time by the FDA. According to Brian Druker, one of the developers of Imatinib, the biggest obstacle to being approved was the name of the drug. At that time, the drug was being called "Glivec", which is also the current spelling in most parts of the world. However, the United States Food and Drug Administration did not want people to mispronounce "Glivec" as /ˈɡlaɪvɛk/ which could be confused with a diabetic drug at the time. Therefore, Novartis, the pharmaceutical company who markets Gleevec, changed the name of "Glivec" to include two "e's" and avoid the phonetic confusion: Gleevec. Shortly thereafter, Gleevec was approved by the FDA.
Costs [edit]
A box of 400-milligram Glivec tablets, as sold in Germany
In 2013, more than 100 cancer specialists published a letter in Blood saying that the prices of many new cancer drugs, including imatinib, is so high that U.S. patients couldn't afford them, and that the level of prices, and profits, was so high as to be immoral. Signatories of the letter included Brian Drucker, Carlo Gambacorti-Asserini, and John Goldman, developers of imatinib. In 2001, imatinib was priced at $30,000 a year, which was based on the price of interferon, then the standard treatment, and would have recouped the development costs in 2 years. After unexpectedly becoming a blockbuster, its price was increased to $92,000 per year in 2012, with annual revenues of $4.7 billion. All its research and development costs were covered in the first $1 billion, and everything else was profit.[39][40] Other doctors have complained about the cost.[41][42][43] For GIST the cost is $64,800 a year.[44]
Prices for a 100 mg pill of Gleevec internationally range from $20 to $30,[45] although generic imatinib is cheaper, as low as $2 per pill.[46]
Legal challenge to generics [edit]
Main article: Novartis v. Union of India & Others
The active pharmaceutical ingredient of Glivec/Gleevec is a specific chemical form of imatinib, namely, the beta polymorph of imatinib mesylate, which exhibits greater stability and bioavailability than the alpha polymorph. A patent for the free base of imatinib was first granted in 1996; Novartis later filed and obtained separate patents for the specific formulation used as the active ingredient of Glivec/Gleevec in several countries.[47] In India, however, such a patent application was rejected in 2005 for a variety of reasons, including lack of novelty and lack of enhanced efficacy; under Section 3(d) of the Indian Patent Act, alternative forms of a chemical compound (including its salts, isomers and crystal polymorphs) are not eligible for patent protection unless they exhibit a difference in efficacy as compared with the parent compound.[47]
In 2007, this rejection of the imatinib patent claim became a test case through which Novartis challenged India's patent laws. A win for Novartis would make it harder for Indian companies to produce generic versions of drugs still manufactured under patent elsewhere in the world. Doctors Without Borders argues a change in law would make it impossible for Indian companies to produce cheap generic antiretrovirals (anti-HIV medication), thus making it impossible for developing countries to buy these essential medicines.[48] On 6 August 2007, the Madras High Court dismissed the writ petition filed by Novartis challenging the constitutionality of Section 3(d) of Indian Patent Act, and deferred to the World Trade Organization (WTO) forum to resolve the TRIPS compliance question. In 2009 Novartis filed a case with the Supreme Court of India challenging the patent denial and the Section 3(d) of Indian Patent Act on the basis that it defined innovation too narrowly. On 1 April 2013, Novartis lost the case.[5] The court cited that the chemical form of imatinib that Novartis wanted to repatent in India is not significantly different from imatinib free base, which had patents that have already expired; hence, Novartis' claim to the patent was considered invalid, as there was no change in efficacy with the new compound that Novartis was trying to patent. This process of repatenting modified formulations of a drug after the original composition of matter patent has expired is an example of evergreening, which is prohibited under Indian patent law. Novartis responded by indicating that it will continue to refrain from research and development activities in India.[49]
See also [edit]
- Discovery and development of Bcr-Abl tyrosine kinase inhibitors
- History of cancer chemotherapy
References [edit]
- ^ Novartis Pharma AG. Gleevec® (imatinib mesylate) tablets prescribing information. East Hanover, NJ; 2006 Sep. Anon. Drugs of choice for cancer. Treat Guidel Med Lett. 2003; 1:41–52
- ^ Goldman, J. M.; Melo, J. V. (2003). "Chronic myeloid leukemia—advances in biology and new approaches to treatment". N Engl J Med 349 (15): 1451–1464. doi:10.1056/NEJMra020777.
- ^ Fausel, C. Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm 64, S9-15 (2007)
- ^ Stegmeier, F., et al. (2010). "Targeted Cancer Therapies in the Twenty-First Century: Lessons From Imatinib." Clin Pharmacol Ther 87(5): 543–552.
- ^ a b "Novartis fails to patent Glivec (Gleevec) in India".
- ^ Rowley to receive Japan Prize for her role in the development of targeted cancer therapy Eurekalert, Press release, 24 January 2012
- ^ Leukemia Drug and Magnet Material Net Japan Prizes by Dennis Normile, Science Insider, 25 January 2012
- ^ Droogendijk HJ, Kluin-Nelemans HJ, van Doormaal JJ, Oranje AP, van de Loosdrecht AA, van Daele PL (July 2006). "Imatinib mesylate in the treatment of systemic mastocytosis: a phase II trial". Cancer 107 (2): 345–51. doi:10.1002/cncr.21996. PMID 16779792.
- ^ a b c "FDA Highlights and Prescribing Information for Gleevec(imatinib mesylate)".
- ^ "Prolonged Use of Imatinib in GIST Patients Leads to New FDA Approval".
- ^ "FDA approves Gleevec for children with acute lymphoblastic leukemia". FDA News Release. US Food and Drug Administration. 25 January 2013. Retrieved 3 April 2013.
- ^ Yang, FC; Ingram, DA; Chen, S; Zhu, Y; Yuan, J; Li, X; Yang, X; Knowles, S et al. (2008). "Nf1-dependent tumors require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow.". Cell 135 (3): 437–48. doi:10.1016/j.cell.2008.08.041. PMC 2788814. PMID 18984156.
|displayauthors=suggested (help) - ^ "Gleevec Holds Potential As First Drug To Successfully Treat Neurofibromatosis, Scientists Report", Science Daily, 31 October 2008
- ^ "Gleevec NF1 Trial". Nfcure.org. Retrieved 2013-04-03.
- ^ "GIST in Neurofibromatosis 1". Gistsupport.org. 2010-05-14. Retrieved 2013-04-03.
- ^ ""Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas (0908-09)" (Suspended)". Clinicaltrials.gov. Retrieved 2013-04-03.
- ^ Tapper EB, Knowles D, Heffron T, Lawrence EC, Csete M (June 2009). "Portopulmonary hypertension: imatinib as a novel treatment and the Emory experience with this condition". Transplant. Proc. 41 (5): 1969–71. doi:10.1016/j.transproceed.2009.02.100. PMID 19545770.
- ^ Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (April 2003). "LRP: role in vascular wall integrity and protection from atherosclerosis". Science 300 (5617): 329–32. doi:10.1126/science.1082095. PMID 12690199.
- ^ Lassila M, Allen TJ, Cao Z, et al. (May 2004). "Imatinib attenuates diabetes-associated atherosclerosis". Arterioscler. Thromb. Vasc. Biol. 24 (5): 935–42. doi:10.1161/01.ATV.0000124105.39900.db. PMID 14988091.
- ^ Reeves PM, Bommarius B, Lebeis S, et al. (July 2005). "Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases". Nat. Med. 11 (7): 731–9. doi:10.1038/nm1265. PMID 15980865.
- ^ He G, Luo W, Li P, et al. (September 2010). "Gamma-secretase activating protein is a therapeutic target for Alzheimer's disease". Nature 467 (7311): 95–8. doi:10.1038/nature09325. PMC 2936959. PMID 20811458.
- ^ "Alzheimer's may start in liver – Health – Alzheimer's Disease | NBC News". MSNBC. Retrieved 2013-01-06.
- ^ Holmes C, Boche D, Wilkinson D, Yadegarfar G, Hopkins V, Bayer A, Jones RW, Bullock R, Love S, Neal JW, Zotova E, Nicoll JAR (July 2008). "Long-term effects of Aβ42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial". The Lancet (Subscription required
|format=requires|url=(help)) 372 (9634): 216–233. doi:10.1016/S0140-6736(08)61075-2. PMID 18640458. - ^ Eliminating Morphine Tolerance – Reformulated Imatinib 23 Feb 2012, 5:00 PST
- ^ "Imatinib". Macmillan Cancer Support. Retrieved 26 December 2012.
- ^ a b Haberfeld, H, ed. (2009). Austria-Codex (in German) (2009/2010 ed.). Vienna: Österreichischer Apothekerverlag. ISBN 3-85200-196-X.
- ^ Kerkelä R, Grazette L, Yacobi R, et al. (August 2006). "Cardiotoxicity of the cancer therapeutic agent imatinib mesylate". Nat. Med. 12 (8): 908–16. doi:10.1038/nm1446. PMID 16862153.
- ^ Shima H, Tokuyama M, Tanizawa A et al (2011). "Distinct impact of imatinib on growth at prepubertal and pubertal ages of children with chronic myeloid leukemia". J. Pediatr 159 (Online): 676–81. doi:10.1016/j.jpeds.2011.03.046. PMID 21592517.
- ^ Scheinfeld N, Schienfeld N (February 2006). "A comprehensive review of imatinib mesylate (Gleevec) for dermatological diseases". J Drugs Dermatol 5 (2): 117–22. PMID 16485879.
- ^ Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach. 11 ed. 2008.
- ^ Gambacorti-Passerini CB, Gunby RH, Piazza R, Galietta A, Rostagno R, Scapozza L (February 2003). "Molecular mechanisms of resistance to imatinib in Philadelphia-chromosome-positive leukaemias". Lancet Oncol. 4 (2): 75–85. doi:10.1016/S1470-2045(03)00979-3. PMID 12573349.
- ^ Deininger MW, Druker BJ (September 2003). "Specific targeted therapy of chronic myelogenous leukemia with imatinib". Pharmacol. Rev. 55 (3): 401–23. doi:10.1124/pr.55.3.4. PMID 12869662.
- ^ Vigneri P, Wang JY (February 2001). "Induction of apoptosis in chronic myelogenous leukemia cells through nuclear entrapment of BCR-ABL tyrosine kinase". Nat. Med. 7 (2): 228–34. doi:10.1038/84683. PMID 11175855.
- ^ Weisberg, Ellen; Paul W. Manley, Sandra W. Cowan-Jacob, Andreas Hochhaus, and James Griffin (2007). "Second Generation Inhibitors of BCR-ABL for the Treatment of Imatinib-resistant Chronic Myeloid Leukaemia.". Nature Reviews Cancer 7 7 (5): 345–56. doi:10.1038/nrc2126.
- ^ Klopp, T, ed. (2010). Arzneimittel-Interaktionen (in German) (2010/2011 ed.). Arbeitsgemeinschaft für Pharmazeutische Information. ISBN 978-3-85200-207-1.
- ^ a b A Conversation With Brian J. Druker, M.D., Researcher Behind the Drug Gleevec by Claudia Dreifus, The New York Times, 2 November 2009
- ^ Gambacorti-Passerini C (2008). "Part I: Milestones in personalised medicine—imatinib". Lancet Oncology 9 (600): 600. doi:10.1016/S1470-2045(08)70152-9. PMID 18510992.
- ^ Druker BJ, Lydon NB (January 2000). "Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia". J. Clin. Invest. 105 (1): 3–7. doi:10.1172/JCI9083. PMC 382593. PMID 10619854.
- ^ Doctors Denounce Cancer Drug Prices of $100,000 a Year By ANDREW POLLACK, New York Times, April 25, 2013
- ^ Price of drugs for chronic myeloid leukemia (CML), reflection of the unsustainable cancer drug prices: perspective of CML Experts Experts in chronic myeloid leukemia, Blood, Published online before print April 25, 2013, doi: 10.1182/blood-2013-03-490003
- ^ Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia". N. Engl. J. Med. 357 (3): 258–65. doi:10.1056/NEJMct071828. PMID 17634461.
- ^ As Pills Treat Cancer, Insurance Lags Behind, By ANDREW POLLACK, New York Times, 14 April 2009
- ^ Living With a Formerly fatal Blood Cancer, By JANE E. BRODY, New York Times, 18 January 2010
- ^ Kelley RK, Venook AP (August 2010). "Nonadherence to imatinib during an economic downturn". N. Engl. J. Med. 363 (6): 596–8. doi:10.1056/NEJMc1004656. PMID 20818898.
- ^ Patented Medicine Review Board (Canada). Report on New Patented Drugs – Gleevec.
- ^ "pharmacychecker.com". pharmacychecker.com. Retrieved 2013-04-03.
- ^ a b Basheer S, Reddy P (2008). "'Ducking' TRIPS in India: A Saga Involving Novartis and the Legality of Section 3(d)". National Law School of India Review 20 (2): 131–55.
- ^ Médecins Sans Frontières. "As Novartis Challenges India's Patent Law, MSF Warns Access to Medicines Is Under Threat", 2006-09-26. Accessed 2013-04-04.
- ^ Kaustubh Kulkarni and Suchitra Mohanty. Novartis loses landmark India cancer drug patent case. Reuters, Mumbai/New Delhi. Mon 1 April 2013.
External links [edit]
- NCI Drug Information Summary for Patients
- Imatinib bound to proteins in the PDB
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- 1. 消化管間質腫瘍に対する補助化学療法および術前補助化学療法としてのイマチニブ adjuvant and neoadjuvant imatinib for gastrointestinal stromal tumors
- 2. 慢性期の慢性骨髄性白血病の初期治療 initial treatment of chronic myeloid leukemia in chronic phase
- 3. 初期治療不奏効後の慢性期における慢性骨髄性白血病の治療 treatment of chronic myeloid leukemia in chronic phase after failure of initial therapy
- 4. 消化管間質腫瘍、平滑筋腫、および消化管の平滑筋肉腫の局所治療 local treatment for gastrointestinal stromal tumors leiomyomas and leiomyosarcomas of the gastrointestinal tract
- 5. 慢性骨髄性白血病の治療の概要 overview of the treatment of chronic myeloid leukemia
English Journal
- Malignant perivascular epithelioid cell tumor in children: description of a case and review of the literature.
- Alaggio R, Cecchetto G, Martignoni G, Bisogno G, Cheng L, Sperlì D, d'Amore ES, Dall'igna P.SourcePathology Department, University of Padua, Padua, Italy.
- Journal of pediatric surgery.J Pediatr Surg.2012 Jun;47(6):e31-40.
- Perivascular epithelioid cell tumors (PEComas) include different morphological entities originating from perivascular epitheliod cells. Their clinical behavior is not predictable, and there are no strict histologic criteria for malignancy, although larger tumors with infiltrative growth, hypercellul
- PMID 22703822
- Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.
- Saponara M, Pantaleo MA, Nannini M, Biasco G.SourceDepartment of Hematology and Oncological Sciences "L.&A.Seragnoli", S.Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy, maristellasaponara@yahoo.it.
- Targeted oncology.Target Oncol.2012 May 17. [Epub ahead of print]
- The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it sh
- PMID 22592950
Japanese Journal
- イマチニブ投与後に腫瘍中心壊死巣が胃内腔と交通した胃原発巨大GISTの1例
- 栗田 信浩,島田 光生,岩田 貴,西岡 将規,吉川 幸造,東島 潤
- 日本臨床外科学会雑誌 = The journal of the Japan Surgical Association 70(4), 1044-1048, 2009-04-25
- NAID 10024956960
- メシル酸イマチニブ投与中発症した消化管穿孔に対して手術を施行し救命しえたgastrointestinal stromal tumorの1例
- 辻浦 誠浩,小泉 範明,當麻 敦史,糸川 嘉樹,植木 孝宜,塚本 賢治,大辻 英吾
- 日本消化器外科学会雑誌 42(3), 276-281, 2009-03-01
- 症例は77歳の女性で,下腹部違和感を主訴に2005年5月当院受診,腹部CT,MRIにて肝腫瘍,腹腔内多発腫瘍,右鼡径部腫瘍を認めた.右鼡径部腫瘍の生検にてgastrointestinal stromal tumor(以下,GIST)と診断され,2005年7月下旬よりメシル酸イマチニブの投与を開始した.2005年9月中旬に腹痛と発熱が出現,腹部CTにてfree airを認めたため,消化管穿孔の診断の …
- NAID 110007122847
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| リンク元 | 「メシル酸イマチニブ」 |
| 関連記事 | 「mesilate」 |