Updating {{drugbox}} (changes to verified fields - updated 'ChEMBL_Ref') per Chem/Drugbox validation (report errors or bugs) |
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{{Short description|Chemical compound}} |
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{{drugbox |
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⚫ | | IUPAC_name |
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<!--Clinical data--> |
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<!--Identifiers--> |
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| synonyms = LY-335979 |
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| CAS_number_Ref = {{cascite|correct|CAS}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| ChemSpiderID = 24599682 |
| ChemSpiderID = 24599682 |
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| SMILES = c1ccc2c(c1)[C@H](c3ccccc3[C@H]4[C@@H]2C4(F)F)N5CCN(CC5)C[C@H](COc6cccc7c6cccn7)O |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D06387 |
| KEGG = D06387 |
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| molecular_weight = 527.61 g/mol |
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<!--Chemical data--> |
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| smiles = Cl.Cl.Cl.FC4(F)[C@@H]3c1ccccc1C(c2c(cccc2)[C@@H]34)N5CCN(CC5)C[C@@H](O)COc7c6cccnc6ccc7 |
| smiles = Cl.Cl.Cl.FC4(F)[C@@H]3c1ccccc1C(c2c(cccc2)[C@@H]34)N5CCN(CC5)C[C@@H](O)COc7c6cccnc6ccc7 |
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'''Zosuquidar''' is a [[Chemical compound|compound]] of [[antineoplastic]] [[drug]] candidates currently under development. It is now in "[[Phase 3]]" of clinical tests in the United States. Its action mechanism consists of the [[Enzyme inhibition|inhibition]] of [[P-glycoprotein]]s; other drugs with this mechanism include [[tariquidar]] and [[laniquidar]]. P-glycoproteins are [[protein]]s which |
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convert the [[energy]] derived from the [[hydrolysis]] of [[Adenosine triphosphate|ATP]] to structural changes in protein molecules, in order to perform [[coupling]], thus discharging [[medicine]] from cells. If P-glycoprotein coded with the MDR1 [[gene]] manifests itself in [[cancer cell]]s, it discharges much of the antineoplastic drugs from the cells, making [[cancer cell]]s [[medicine tolerance|medicine tolerant]], and rendering antineoplastic drugs ineffective. This protein also manifests itself in normal organs not affected by the cancer (such as the liver, small intestine, and skin cells in blood vessels of the brain), and participates in the transportation of medicine. The compound Zosuquidar inhibits this P-glycoprotein, causing the cancer cells to lose their medicine tolerance, and making antineoplastic drugs effective. |
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'''Zosuquidar''' (development code '''LY-335979''') is an experimental [[antineoplastic]] [[drug]].<ref>{{cite web | url = https://www.cancer.gov/publications/dictionaries/cancer-drug/def/zosuquidar-trihydrochloride | title = Zosuquidar trihydrochloride | work = NCI Drug Dictionary | publisher = [[National Cancer Institute]] }}</ref> Zosquidir [[Enzyme inhibition|inhibits]] [[P-glycoprotein]]s.<ref name=Cripe>{{cite journal | vauthors = Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, Rowe JM, Lazarus HM, Luger S, Tallman MS | display-authors = 6 | title = Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999 | journal = Blood | volume = 116 | issue = 20 | pages = 4077–4085 | date = November 2010 | pmid = 20716770 | pmc = 2993615 | doi = 10.1182/blood-2010-04-277269 }}</ref> Other drugs with this mechanism include [[tariquidar]] and [[laniquidar]]. P-glycoproteins are trans-membrane [[protein]]s that pump foreign substances out of cells in an [[Adenosine triphosphate|ATP]] dependent fashion. Cancers overexpressing P-glycoproteins are able to pump out therapeutic molecules before they are able to reach their target, effectively making the cancer multi-drug resistant. Zosuquidar inhibits P-glycoproteins, inhibiting the efflux pump and restoring sensitivity to chemotherapeutic agents.<ref name=Cripe/> |
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{{Unreferenced|date =September 2007}} |
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<references/> |
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Zosuqidar was initially characterized by Syntex Corporation, which was acquired by [[Hoffmann-La Roche|Roche]] in 1990. Roche licensed the drug to [[Eli Lilly]] in 1997. It was granted [[orphan drug status]] by the FDA in 2006 for AML. In 2010, it was announced that a [[phase III clinical trial]] for the treatment of [[acute myeloid leukemia]] (AML) and [[myelodysplastic syndrome]] did not meet its primary endpoint<ref>{{ClinicalTrialsGov|NCT00046930|Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia}}</ref> and Eli Lilly discontinued its development.<ref>{{cite web | url = https://adisinsight.springer.com/drugs/800005159 | title = Zosuquidar - Kanisa Pharmaceuticals | work = Adis Insight | publisher = Springer Nature Switzerland AG }}</ref> |
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[[Category:Chemotherapeutic agents]] |
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{{Reflist}} |
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[[Category:Experimental cancer drugs]] |
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[[Category:Organofluorides]] |
[[Category:Organofluorides]] |
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[[Category:Cyclopropanes]] |
[[Category:Cyclopropanes]] |
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[[Category:Quinolines]] |
[[Category:Quinolines]] |
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[[Category:Piperazines]] |
[[Category:Piperazines]] |
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[[Category:Abandoned drugs]] |
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[[ja:ゾスキダル]] |
Revision as of 13:37, 11 July 2023
Clinical data | |
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Other names | LY-335979 |
ATC code |
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CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.236.552 |
Chemical and physical data | |
Formula | C32H31F2N3O2 |
Molar mass | 527.616 g·mol−1 |
3D model (JSmol) | |
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(what is this?) (verify) |
Zosuquidar (development code LY-335979) is an experimental antineoplastic drug.[1] Zosquidir inhibits P-glycoproteins.[2] Other drugs with this mechanism include tariquidar and laniquidar. P-glycoproteins are trans-membrane proteins that pump foreign substances out of cells in an ATP dependent fashion. Cancers overexpressing P-glycoproteins are able to pump out therapeutic molecules before they are able to reach their target, effectively making the cancer multi-drug resistant. Zosuquidar inhibits P-glycoproteins, inhibiting the efflux pump and restoring sensitivity to chemotherapeutic agents.[2]
Zosuqidar was initially characterized by Syntex Corporation, which was acquired by Roche in 1990. Roche licensed the drug to Eli Lilly in 1997. It was granted orphan drug status by the FDA in 2006 for AML. In 2010, it was announced that a phase III clinical trial for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome did not meet its primary endpoint[3] and Eli Lilly discontinued its development.[4]
References
- ^ "Zosuquidar trihydrochloride". NCI Drug Dictionary. National Cancer Institute.
- ^ a b Cripe LD, Uno H, Paietta EM, Litzow MR, Ketterling RP, Bennett JM, et al. (November 2010). "Zosuquidar, a novel modulator of P-glycoprotein, does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized, placebo-controlled trial of the Eastern Cooperative Oncology Group 3999". Blood. 116 (20): 4077–4085. doi:10.1182/blood-2010-04-277269. PMC 2993615. PMID 20716770.
- ^ Clinical trial number NCT00046930 for "Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia" at ClinicalTrials.gov
- ^ "Zosuquidar - Kanisa Pharmaceuticals". Adis Insight. Springer Nature Switzerland AG.