Imatinib Encyclopedia Information

7/29/2019 Imatinib Encyclopedia Information

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Imatinib 1

Imatinib

Imatinib

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[1]

MedlinePlus a606018[2]

Licence data

EMA:Link

[3]

, US FDA:link

[4]

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[5]

220127-57-1[6]

(mesilate)

ATC code L01XE01[7]

PubChem CID 5291[8]

DrugBank DB00619[9]

ChemSpider 5101[10]
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Imatinib 2

UNII BKJ8M8G5HI[11]

KEGG D08066[12]

ChEBI CHEBI:45783[13]

ChEMBL CHEMBL941[14]

Chemical data

Formula C29

H31

N7O

Mol. mass 493.603 g/mol

589.7 g/mol (mesilate)

(what is this?) (verify)[15]

Imatinib (Imatinib Mesylate), marketed by Novartis as Gleevec (USA) or Glivec (Europe/Australia/Latin America),

is a competitive tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably of which includes

Philadelphia Chromosome positive (Ph+

) Chronic Myelogenous Leukemia (CML).[16]

Like all tyrosine-kinaseinhibitors, Imatinib works by blocking a central tyrosine kinase enzyme, in this case, BCR-ABL from

phosphorylating subsequent proteins and initiating the signaling cascade necessary for cancer development. [17]

Because the BCR-ABL tyrosine kinase enzyme exists only in cancer cells and not in healthy cells, Imatinib is able to

function as a targeted cancer therapyonly cancer cells are killed through the drug's action.[18] In this regard,

Imatinib was one of the first cancer therapies to show the potential for such targeted action and of is often cited as a

paradigm for research in cancer therapeutics[19]

Due to the success of Imatinib, the developers of drug were awarded the Lasker Award in 2009 and the Japan Prize

in 2012.[20][21]

History

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.[22] Druker led the clinical trials confirming its efficacy in CML.[23]

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.[24]

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".[22]

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 "GLIE-VEC" 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.
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Imatinib 3

Uses

Clinical

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.[25]

Experience has shown, however, thatimatinib is much less effective in patients with this mutation, and patients with the mutation comprise nearly 90% of

cases of mastocytosis.

Chronic myelogenous leukemia

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.[26]

Gastrointestinal stromal tumors

The FDA first granted approval for advanced GIST patients in 2002. On February 1st, 2012, imatinib was approvedfor use after the surgical removal of KIT-positive tumors to help prevent recurrence. [27] The drug is also approved in

unresectable KIT-positive GISTs.[26]

Other approvals

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-PDGFR

fusion kinase (CHIC2 allele deletion) or FIP1L1-PDGFR fusion kinase negative or unknown, unresectable,

recurrent and/or metastatic dermatofibrosarcoma protuberans.[26]

Plexiform neurofibromas

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.[28][29][30][31][32]

Experimental

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.[33] 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-R). One of its effects is delaying

atherosclerosis in mice without[34] or with diabetes.[35]

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.[36]

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 bloodbrain barrier are potential therapeutic agents for

treating Alzheimer's disease.[37] Another study suggests that imatinib may not need to cross the bloodbrain barrier

to be effective at treating Alzheimer's, as the research indicates the production of beta-amyloid may begin in theliver. Tests on mice indicate that imatinib is effective at reducing beta-amyloid in the brain.[38] It is not known
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Imatinib 4

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.[39]

A formulation of imatinib with a cyclodextrin (Captisol) as a carrier to overcome the bloodbrain barrier is also

currently considered as an experimental drug for lowering and reversing opioid tolerance. Imatinib has shown

reversal of tolerance in rats.[40] Imatinib is an experimental drug in the treatment of desmoid tumor or aggressive

fibromatosis.

Adverse effects

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;[41] weight gain, reduced number of blood

cells (neutropenia, thrombocytopenia, anemia), headache, and

edema.[42]

Severe congestive cardiac failure is an uncommon but recognized sideeffect of imatinib and mice treated with large doses of imatinib show

toxic damage to their myocardium.[43]

If imatinib is used in prepubescent children, it can delay normal

growth, although a proportion will experience catch-up growth during

puberty.[44]

Pharmacology

Pharmacokinetics

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.[45]

Mechanism of action

Imatinib is a 2-phenylaminopyrimidine derivative that functions as a

specific inhibitor of a number of tyrosine kinase enzymes. It occupies

the TKactive 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).
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Imatinib 5

In chronic myelogenous leukemia, the Philadelphia chromosome leads to a fusion protein ofabl 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 aclosed or self-inhibited conformation, and therefore inhibiting the enzyme activity of the protein

semi-competitively.[46] This fact explains why many BCR-ABL mutations can cause resistance to imatinib by

shifting its equilibrium toward the open or active conformation.[47]

Imatinib is quite selective for bcr-ablit 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.[48] 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. [49]

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.[50]

Interactions

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.[42]

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.[51]

Costs

A box of 400-milligram Glivec tablets, as sold in

Germany

The cost of Gleevec for CML has ranged from $32,000[52][53] to

$98,000[54] a year, and for GIST is $64,800 a year.[55]

Prices for a 100 mg pill of Gleevec internationally range from $20 to

$30,[56] although generic imatinib is cheaper.[57]

Legal challenge to generics

In 2007, imatinib became a test case through which Novartis

challenged India's patent laws. A win for Novartis would make it
http://en.wikipedia.org/w/index.php?title=Indiahttp://en.wikipedia.org/w/index.php?title=Test_casehttp://en.wikipedia.org/w/index.php?title=File%3AGlivec_400mg.jpghttp://en.wikipedia.org/w/index.php?title=Toxoidhttp://en.wikipedia.org/w/index.php?title=Inactivated_vaccinehttp://en.wikipedia.org/w/index.php?title=Live_vaccinehttp://en.wikipedia.org/w/index.php?title=Levothyroxinhttp://en.wikipedia.org/w/index.php?title=Paracetamolhttp://en.wikipedia.org/w/index.php?title=Metoprololhttp://en.wikipedia.org/w/index.php?title=Warfarinhttp://en.wikipedia.org/w/index.php?title=Pimozidehttp://en.wikipedia.org/w/index.php?title=Ciclosporinhttp://en.wikipedia.org/w/index.php?title=Simvastatinhttp://en.wikipedia.org/w/index.php?title=St._John%27s_Worthttp://en.wikipedia.org/w/index.php?title=Rifampicinhttp://en.wikipedia.org/w/index.php?title=Grapefruit_juicehttp://en.wikipedia.org/w/index.php?title=Clarithromycinhttp://en.wikipedia.org/w/index.php?title=Itraconazolehttp://en.wikipedia.org/w/index.php?title=Ketoconazolehttp://en.wikipedia.org/w/index.php?title=Apoptosishttp://en.wikipedia.org/w/index.php?title=Cancer_cellhttp://en.wikipedia.org/w/index.php?title=Tyrosine_kinasehttp://en.wikipedia.org/w/index.php?title=Enzyme_inhibitorhttp://en.wikipedia.org/w/index.php?title=Phosphorylationhttp://en.wikipedia.org/w/index.php?title=Substrate_%28biochemistry%29http://en.wikipedia.org/w/index.php?title=Tyrosinehttp://en.wikipedia.org/w/index.php?title=Phosphatehttp://en.wikipedia.org/w/index.php?title=Catalysishttp://en.wikipedia.org/w/index.php?title=Adenosine_triphosphatehttp://en.wikipedia.org/w/index.php?title=Binding_sitehttp://en.wikipedia.org/w/index.php?title=Active_sitehttp://en.wikipedia.org/w/index.php?title=Tyrosine_kinasehttp://en.wiktionary.org/wiki/constitutivehttp://en.wikipedia.org/w/index.php?title=Philadelphia_chromosomehttp://en.wikipedia.org/w/index.php?title=Chronic_myelogenous_leukemia


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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 Third World countries to buy

these essential medicines.[58] 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. As of 2009 India has refused to grant patent exclusivity. .

References

[1] http:/ /www.drugs. com/monograph/gleevec.html

[2] http:/ /www.nlm.nih. gov/medlineplus/druginfo/meds/a606018. html

[3] http:/ /www.ema. europa. eu/ema/index. jsp?curl=/pages/medicines/landing/epar_search.jsp&murl=menus/medicines/medicines.jsp&

searchkwByEnter=true& status=Authorised&keyword=Glivec& searchType=Name& jsenabled=true

[4] http:/ /www.accessdata.fda. gov/scripts/cder/drugsatfda/index. cfm?fuseaction=Search.SearchAction&SearchTerm=IMATINIB&

SearchType=BasicSearch

[5] http:/ /www.nlm.nih. gov/cgi/mesh/2009/MB_cgi?term=152459-95-5& rn=1

[6] http:/ /toolserver. org/~magnus/cas.php?language=en& cas=220127-57-1& title=

[7] http:/ /www.whocc. no/atc_ddd_index/?code=L01XE01

[8] http:/ /pubchem. ncbi.nlm. nih. gov/summary/summary.cgi?cid=5291

[9] http:/ /www.drugbank. ca/drugs/DB00619

[10] http://www.chemspider.com/Chemical-Structure.5101

[11] http://fdasis.nlm.nih. gov/srs/srsdirect.jsp?regno=BKJ8M8G5HI

[12] http://www.kegg. jp/entry/D08066

[13] https://www.ebi. ac.uk/chebi/searchId.do?chebiId=CHEBI:45783

[14] https://www.ebi. ac.uk/chembldb/index.php/compound/inspect/CHEMBL941

[15] http://en. wikipedia.org/wiki/Special%3Acomparepages?rev1=459451238& page2=%3AImatinib

[16][16] 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

[17] Goldman, J.M. & Melo, J.V. Chronic myeloid leukemia--advances in biology and new approaches to treatment. N Engl J Med 349,

1451-1464 (2003)

[18][18] Fausel, C. Targeted chronic myeloid leukemia therapy: Seeking a cure. Am J Health Syst Pharm 64, S9-15 (2007)[19][19] Stegmeier, F., et al. (2010). "Targeted Cancer Therapies in the Twenty-First Century: Lessons From Imatinib." Clin Pharmacol Ther 87(5):

543-552.

[20] Rowley to receive Japan Prize for her role in the development of targeted cancer therapy (http://www.eurekalert.org/pub_releases/

2012-01/uocm-rtr012312. php) Eurekalert, Press release, 24-Jan-2012

[21] Leukemia Drug and Magnet Material Net Japan Prizes (http://news.sciencemag.org/scienceinsider/2012/01/

leukemia-drug-and-magnet-materia. html?ref=hp) by Dennis Normile, Science Insider, 25 January 2012

[22] A Conversation With Brian J. Druker, M.D., Researcher Behind the Drug Gleevec (http://www.nytimes.com/2009/11/03/science/

03conv. html) by Claudia Dreifus, The New York Times, November 2, 2009

[23] Gambacorti-Passerini C (2008). "Part I: Milestones in personalised medicine--imatinib".Lancet Oncology9 (600): 600.

doi:10.1016/S1470-2045(08)70152-9. PMID 18510992.

[24] Druker BJ, Lydon NB (January 2000). "Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous

leukemia" (http:/

/

www.

jci.

org/

cgi/

content/

full/

105/

1/

3).J. Clin. Invest.105 (1): 3

7. doi:10.1172/JCI9083. PMC 382593.PMID 10619854. .

[25] 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". Cancer107 (2): 34551. doi:10.1002/cncr.21996. PMID 16779792.

[26] "FDA Highlights and Prescribing Information for Gleevec(imatinib mesylate)" (http://www.accessdata.fda. gov/drugsatfda_docs/label/

2008/021588s024lbl. pdf). .

[27] "Prolonged Use of Imatinib in GIST Patients Leads to New FDA Approval" (http://www.onclive.com/web-exclusives/

Prolonged-Use-of-Imatinib-in-GIST-Patients-Leads-to-New-FDA-Approval). .

[28] 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.". Cell135 (3): 43748. doi:10.1016/j.cell.2008.08.041.

PMC 2788814. PMID 18984156.

[29] "Gleevec Holds Potential As First Drug To Successfully Treat Neurofibromatosis, Scientists Report", [[Science Daily (http://www.

sciencedaily.com/releases/2008/10/081030123837. htm)], October 31, 2008]

[30] "Gleevec NF1 Trial" (http://www.nfcure. org/newnf1trial/gleevecnf1trial.html)

[31] "GIST in Neurofibromatosis 1" (http://www.gistsupport.org/about-gist/gist-in-neurofibromatosis-1. php)
http://www.gistsupport.org/about-gist/gist-in-neurofibromatosis-1.phphttp://www.gistsupport.org/about-gist/gist-in-neurofibromatosis-1.phphttp://www.nfcure.org/newnf1trial/gleevecnf1trial.htmlhttp://www.sciencedaily.com/releases/2008/10/081030123837.htmhttp://www.sciencedaily.com/releases/2008/10/081030123837.htmhttp://www.onclive.com/web-exclusives/Prolonged-Use-of-Imatinib-in-GIST-Patients-Leads-to-New-FDA-Approvalhttp://www.onclive.com/web-exclusives/Prolonged-Use-of-Imatinib-in-GIST-Patients-Leads-to-New-FDA-Approvalhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdfhttp://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021588s024lbl.pdfhttp://www.jci.org/cgi/content/full/105/1/3http://en.wikipedia.org/w/index.php?title=Claudia_Dreifushttp://www.nytimes.com/2009/11/03/science/03conv.htmlhttp://www.nytimes.com/2009/11/03/science/03conv.htmlhttp://news.sciencemag.org/scienceinsider/2012/01/leukemia-drug-and-magnet-materia.html?ref=hphttp://news.sciencemag.org/scienceinsider/2012/01/leukemia-drug-and-magnet-materia.html?ref=hphttp://www.eurekalert.org/pub_releases/2012-01/uocm-rtr012312.phphttp://www.eurekalert.org/pub_releases/2012-01/uocm-rtr012312.phphttp://en.wikipedia.org/wiki/Special%3Acomparepages?rev1=459451238&page2=%3AImatinibhttps://www.ebi.ac.uk/chembldb/index.php/compound/inspect/CHEMBL941https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:45783http://www.kegg.jp/entry/D08066http://fdasis.nlm.nih.gov/srs/srsdirect.jsp?regno=BKJ8M8G5HIhttp://www.chemspider.com/Chemical-Structure.5101http://www.drugbank.ca/drugs/DB00619http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=5291http://www.whocc.no/atc_ddd_index/?code=L01XE01http://toolserver.org/~magnus/cas.php?language=en&cas=220127-57-1&title=http://www.nlm.nih.gov/cgi/mesh/2009/MB_cgi?term=152459-95-5&rn=1http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchTerm=IMATINIB&SearchType=BasicSearchhttp://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.SearchAction&SearchTerm=IMATINIB&SearchType=BasicSearchhttp://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/landing/epar_search.jsp&murl=menus/medicines/medicines.jsp&searchkwByEnter=true&status=Authorised&keyword=Glivec&searchType=Name&jsenabled=truehttp://www.ema.europa.eu/ema/index.jsp?curl=/pages/medicines/landing/epar_search.jsp&murl=menus/medicines/medicines.jsp&searchkwByEnter=true&status=Authorised&keyword=Glivec&searchType=Name&jsenabled=truehttp://www.nlm.nih.gov/medlineplus/druginfo/meds/a606018.htmlhttp://www.drugs.com/monograph/gleevec.htmlhttp://en.wikipedia.org/w/index.php?title=TRIPShttp://en.wikipedia.org/w/index.php?title=World_Trade_Organizationhttp://en.wikipedia.org/w/index.php?title=Indian_Patent_Acthttp://en.wikipedia.org/w/index.php?title=Madras_High_Courthttp://en.wikipedia.org/w/index.php?title=Essential_medicineshttp://en.wikipedia.org/w/index.php?title=HIVhttp://en.wikipedia.org/w/index.php?title=M%C3%A9decins_Sans_Fronti%C3%A8reshttp://en.wikipedia.org/w/index.php?title=Generic_drugs


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Imatinib 7

[32] "Pilot Study of Gleevec/Imatinib Mesylate (STI-571, NSC 716051) in Neurofibromatosis (NF1) Patient With Plexiform Neurofibromas

(0908-09)" (Suspended) (http://clinicaltrials.gov/ct2/show/NCT01140360)

[33] 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): 196971. doi:10.1016/j.transproceed.2009.02.100. PMID 19545770.

[34] Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (April 2003). "LRP: role in vascular wall integrity and protection from

atherosclerosis". Science300 (5617): 32932. doi:10.1126/science.1082095. PMID 12690199.

[35] Lassila M, Allen TJ, Cao Z, et al. (May 2004). "Imatinib attenuates diabetes-associated atherosclerosis".Arterioscler. Thromb. Vasc. Biol.

24 (5): 93542. doi:10.1161/01.ATV.0000124105.39900.db. PMID 14988091.[36] Reeves PM, Bommarius B, Lebeis S, et al. (July 2005). "Disabling poxvirus pathogenesis by inhibition of Abl-family tyrosine kinases". Nat.

Med.11 (7): 7319. doi:10.1038/nm1265. PMID 15980865.

[37] 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): 958. doi:10.1038/nature09325. PMC 2936959. PMID 20811458.

[38] "Alzheimer's may start in liver - Health - Alzheimer's Disease | NBC News" (http://www.msnbc. msn.com/id/41971124/ns/

health-alzheimers_disease/). MSNBC. . Retrieved 2013-01-06.

[39] 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 A42 immunisation in Alzheimer's disease: follow-up of a randomised, placebo-controlled phase I trial"

(Subscription required). The Lancet372 (9634): 216233. doi:10.1016/S0140-6736(08)61075-2. PMID 18640458.

[40] Eliminating Morphine Tolerance - Reformulated Imatinib (http://www.medicalnewstoday. com/articles/242064. php) 23 Feb 2012, 5:00

PST

[41] "Imatinib" (http:/

/

www.

macmillan.

org.

uk/

Cancerinformation/

Cancertreatment/

Treatmenttypes/

Biologicaltherapies/Cancergrowthinhibitors/Imatinib.aspx#DynamicJumpMenuManager_6_Anchor_3). Macmillan Cancer Support. . Retrieved 26 December

2012.

[42] Haberfeld, H, ed. (2009) (in German).Austria-Codex (2009/2010 ed.). Vienna: sterreichischer Apothekerverlag. ISBN 3-85200-196-X.

[43] Kerkel R, Grazette L, Yacobi R, et al. (August 2006). "Cardiotoxicity of the cancer therapeutic agent imatinib mesylate".Nat. Med.12 (8):

90816. doi:10.1038/nm1446. PMID 16862153.

[44] 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. Pediatr159 (Online): 67681. doi:10.1016/j.jpeds.2011.03.046. PMID 21592517.

[45] Scheinfeld N, Schienfeld N (February 2006). "A comprehensive review of imatinib mesylate (Gleevec) for dermatological diseases".J

Drugs Dermatol5 (2): 11722. PMID 16485879.

[46] Takimoto CH, Calvo E. "Principles of Oncologic Pharmacotherapy" (http://www.cancernetwork. com/cancer-management-11/chapter03/

article/10165/1402628) in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) Cancer Management: A Multidisciplinary Approach

(http://www.cancernetwork. com/cancer-management-11/). 11 ed. 2008.

[47] 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): 7585. doi:10.1016/S1470-2045(03)00979-3.

PMID 12573349.

[48] Deininger MW, Druker BJ (September 2003). "Specific targeted therapy of chronic myelogenous leukemia with imatinib".Pharmacol. Rev.

55 (3): 40123. doi:10.1124/pr.55.3.4. PMID 12869662.

[49] 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): 22834. doi:10.1038/84683. PMID 11175855.

[50] 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 77 (5): 34556.

doi:10.1038/nrc2126.

[51] Klopp, T, ed. (2010) (in German).Arzneimittel-Interaktionen (2010/2011 ed.). Arbeitsgemeinschaft fr Pharmazeutische Information.

ISBN 978-3-85200-207-1.

[52] Schiffer CA (July 2007). "BCR-ABL tyrosine kinase inhibitors for chronic myelogenous leukemia".N. Engl. J. Med.357 (3): 25865.doi:10.1056/NEJMct071828. PMID 17634461.

[53] As Pills Treat Cancer, Insurance Lags Behind (http://www.nytimes. com/2009/04/15/business/15pill. html), By ANDREW POLLACK,

New York Times, April 14, 2009

[54] Living With a Formerly fatal Blood Cancer (http://www.nytimes.com/2010/01/19/health/19brod. html), By JANE E. BRODY, New

York Times, January 18, 2010

[55] Kelley RK, Venook AP (August 2010). "Nonadherence to imatinib during an economic downturn".N. Engl. J. Med.363 (6): 5968.

doi:10.1056/NEJMc1004656. PMID 20818898.

[56] Patented Medicine Review Board (Canada). (http://www.pmprb-cepmb. gc.ca/english/View.asp?x=529& mp=572) Report on New

Patented Drugs - Gleevec.

[57] pharmacychecker.com (http://www.pharmacychecker. com/listing.asp?criteria_2=imatinib& Search=1&x=51& y=14)

[58] Mdecins Sans Frontires. "As Novartis Challenges India's Patent Law, MSF Warns Access to Medicines Is Under Threat"(http://www.

doctorswithoutborders. org/pr/2006/09-26-2006_1. cfm), 2006-09-26. Accessed 2006-02-10.
http://www.doctorswithoutborders.org/pr/2006/09-26-2006_1.cfmhttp://www.doctorswithoutborders.org/pr/2006/09-26-2006_1.cfmhttp://en.wikipedia.org/w/index.php?title=M%C3%A9decins_Sans_Fronti%C3%A8reshttp://www.pharmacychecker.com/listing.asp?criteria_2=imatinib&Search=1&x=51&y=14http://www.pmprb-cepmb.gc.ca/english/View.asp?x=529&mp=572http://www.nytimes.com/2010/01/19/health/19brod.htmlhttp://www.nytimes.com/2009/04/15/business/15pill.htmlhttp://www.cancernetwork.com/cancer-management-11/http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biologicaltherapies/Cancergrowthinhibitors/Imatinib.aspx#DynamicJumpMenuManager_6_Anchor_3http://www.macmillan.org.uk/Cancerinformation/Cancertreatment/Treatmenttypes/Biologicaltherapies/Cancergrowthinhibitors/Imatinib.aspx#DynamicJumpMenuManager_6_Anchor_3http://www.medicalnewstoday.com/articles/242064.phphttp://www.msnbc.msn.com/id/41971124/ns/health-alzheimers_disease/http://www.msnbc.msn.com/id/41971124/ns/health-alzheimers_disease/http://clinicaltrials.gov/ct2/show/NCT01140360


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External links

NCI Drug Information Summary for Patients (http://www.cancer.gov/cancertopics/druginfo/

imatinibmesylate)

Imatinib bound to proteins (http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=STI) in the PDB
http://en.wikipedia.org/w/index.php?title=Protein_Data_Bankhttp://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=STIhttp://www.cancer.gov/cancertopics/druginfo/imatinibmesylatehttp://www.cancer.gov/cancertopics/druginfo/imatinibmesylate


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Article Sources and ContributorsImatinib Source: http://en.wikipedia.org/w/index.php?oldid=531541690 Contributors: 100-bit-machine, A2-25, Aboutmovies, Afterlaws, AlanBarrett, Alice.odin, Alteripse, Alvis, Andries,

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Chemgirl131, Chris Howard, Chris the speller, Cortamears, Daevatgl, Diberri, Dogcow, Doseiai2, Edgar181, Eleassar, Eloquence, Enkephalin, Eric Kvaalen, Erxnmedia, Fusion114, Fusion57,

Fuzbaby, Fvasconcellos, Gak, Gigemag76, Gleevec, Gubernator, Gyrofrog, Gzornenplatz, Harijay, Hazard-SJ, HazyM, Hinemash6, Holeung, Hoverflysmiles, IEEE, JWSchmidt, JeremyA,

Jfdwolff, Joherz, Julesd, Jyril, Katnap01, Kjc2002, Ksheka, Lian053, Linberry, Little green rosetta, Louisajb, Lupin, Martin451, MattKingston, Melaen, Michelle stone1, Nagelfar, Nbauman,

Nderive, Niceguyedc, Njwyf16, Nohat, Norman21, OHSUKnight, OR Bear, Ozybolairy, Pashihiko, Petersam, P ip2andahalf, Pvosta, Quietvillager, Rbethune, Richard Arthur Norton (1958- ),

Rod57, Rosalien, Rt34rt34, Rytyho usa, SDC, Sakurambo, SanderB, Selket, Silvaneus, Simplepink, Slambo, Smithbrenon, Snapperman2, Sodium, Spiff666, Stillwaterising, Tavilis, Techelf,TestPilot, TimVickers, TranMH, TylerDurden8823, Vogon77, Wyvern t, Yathirajancrystal, , 136 anonymous edits

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