PROFILBARU.COM

Pemetreksed
Klinički podaci
AHFS/Drugs.com	Monografija
Identifikatori
CAS broj	150399-23-8
ATC kod	L01BA04
PubChem	60843
DrugBank	DB00642
ChemSpider	54830
ChEMBL	CHEMBL225072
Hemijski podaci
Formula	C20H21N5O6
Mol. masa	427,411
SMILES	eMolekuli & PubHem
InChI
	InChI=1S/C20H21N5O6/c21-20-24-16-15(18(29)25-20)12(9-22-16)6-3-10-1-4-11(5-2-10)17(28)23-13(19(30)31)7-8-14(26)27/h1-2,4-5,9,13H,3,6-8H2,(H,23,28)(H,26,27)(H,30,31)(H4,21,22,24,25,29)/t13-/m1/s1; Key: WBXPDJSOTKVWSJ-CYBMUJFWSA-N
Farmakokinetički podaci
Poluvreme eliminacije	3,5 h
Farmakoinformacioni podaci
Trudnoća	?
Pravni status
Način primene	Intravenozno

Pemetreksed (prodajni naziv Alimta) je hemoterapijski lek koji proizvodi i prodaje preduzeće Eli Lilly and Company. Njegove indikacije su tretman raka pleuralnog mezotelioma i makrocelularnog karcinoma pluća.

Pemetreksed je organsko jedinjenje, koje sadrži 20 atoma ugljenika i ima molekulsku masu od 427,411 Da.^[5]^[6]^[7]^[8]^[9]^[10]

Mehanizam dejstva

Pemetreksed je hemijski sličan folnoj kiselina i pripada klasi hemoterapijskih lekova zvanih folatni antimetaboliti. On deluje putem inhibiranja tri enzima koji se koriste u sintezi purina i pirimidina —timidilatna sintaza (TS), dihidrofolatna reduktaza (DHFR), i glicinamid ribonukleotidna formiltransferaza^[11]^[12] (GARFT). Putem inhibiranja formiranja prekursora purinskih i pirimidinskih nukleotida, pemetreksed sprečava formiranje DNK i RNK, koje su neophodne za rast i opstanak normalnih i kanceroznih ćelija.

Osobine

Osobina	Vrednost
Broj akceptora vodonika	9
Broj donora vodonika	6
Broj rotacionih veza	9
Particioni koeficijent^[13] (ALogP)	1,1
Rastvorljivost^[14] (logS, log(mol/L))	-4,5
Polarna površina^[15] (PSA, Å²)	187,0

Reference

↑ Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit
↑ Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.
↑ Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit
↑ Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit
↑ Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. PMID 16291410
↑ Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic] Bull Cancer. 2007;94 Spec No Actualites:S134-8. PMID 17845983
↑ Fuld AD, Dragnev KH, Rigas JR: Pemetrexed in advanced non-small-cell lung cancer. Expert Opin Pharmacother. 2010 Jun;11(8):1387-402. PMID 20446853
↑ Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. PMID 12722874
↑ Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS (2011). „DrugBank 3.0: a comprehensive resource for omics research on drugs”. Nucleic Acids Res. 39 (Database issue): D1035-41. DOI:10.1093/nar/gkq1126. PMC 3013709. PMID 21059682. edit
↑ David S. Wishart, Craig Knox, An Chi Guo, Dean Cheng, Savita Shrivastava, Dan Tzur, Bijaya Gautam, and Murtaza Hassanali (2008). „DrugBank: a knowledgebase for drugs, drug actions and drug targets”. Nucleic Acids Res 36 (Database issue): D901-6. DOI:10.1093/nar/gkm958. PMC 2238889. PMID 18048412. edit
↑ McLeod, Howard L.; James Cassidy, Robert H. Powrie, David G. Priest, Mark A. Zorbas, Timothy W. Synold, Stephen Shibata, Darcy Spicer, Donald Bissett, Yazdi K. Pithavala, Mary A. Collier, Linda J. Paradiso, John D. Roberts (Jul 2000). „Pharmacokinetic and Pharmacodynamic Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitor AG2034”. Clinical Cancer Research 6 (7): 2677–84. PMID 10914709.
↑ Avendano, Carmen; Menendez, J. Carlos (April 2008). Medicinal Chemistry of Anticancer Drugs. Amsterdam: Elsevier. str. 37. ISBN 0-444-52824-5.
↑ Ghose, A.K., Viswanadhan V.N., and Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A 102: 3762-3772. DOI:10.1021/jp980230o.
↑ Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488-1493. DOI:10.1021/ci000392t. PMID 11749573. edit
↑ Ertl P., Rohde B., Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714-3717. DOI:10.1021/jm000942e. PMID 11020286. edit

Literatura

Hardman JG, Limbird LE, Gilman AG. (2001). Goodman & Gilman's The Pharmacological Basis of Therapeutics (10 izd.). New York: McGraw-Hill. DOI:10.1036/0071422803. ISBN 0-07-135469-7.
Thomas L. Lemke, David A. Williams, ur. (2007). Foye's Principles of Medicinal Chemistry (6 izd.). Baltimore: Lippincott Willams & Wilkins. ISBN 0-7817-6879-9.

Vanjske veze

	Portal Medicina
	Portal Hemija

Pemetrexed

[1] Li Q, Cheng T, Wang Y, Bryant SH (2010). „PubChem as a public resource for drug discovery.”. Drug Discov Today 15 (23-24): 1052-7. DOI:10.1016/j.drudis.2010.10.003. PMID 20970519. edit

[2] Evan E. Bolton, Yanli Wang, Paul A. Thiessen, Stephen H. Bryant (2008). „Chapter 12 PubChem: Integrated Platform of Small Molecules and Biological Activities”. Annual Reports in Computational Chemistry 4: 217-241. DOI:10.1016/S1574-1400(08)00012-1.

[3] Hettne KM, Williams AJ, van Mulligen EM, Kleinjans J, Tkachenko V, Kors JA. (2010). „Automatic vs. manual curation of a multi-source chemical dictionary: the impact on text mining”. J Cheminform 2 (1): 3. DOI:10.1186/1758-2946-2-3. PMID 20331846. edit

[4] Gaulton A, Bellis LJ, Bento AP, Chambers J, Davies M, Hersey A, Light Y, McGlinchey S, Michalovich D, Al-Lazikani B, Overington JP. (2012). „ChEMBL: a large-scale bioactivity database for drug discovery”. Nucleic Acids Res 40 (Database issue): D1100-7. DOI:10.1093/nar/gkr777. PMID 21948594. edit

[5] Rollins KD, Lindley C: Pemetrexed: a multitargeted antifolate. Clin Ther. 2005 Sep;27(9):1343-82. PMID 16291410

[6] Lansiaux A, Lokiec F: [Pemetrexed: from preclinic to clinic] Bull Cancer. 2007;94 Spec No Actualites:S134-8. PMID 17845983

[7] Fuld AD, Dragnev KH, Rigas JR: Pemetrexed in advanced non-small-cell lung cancer. Expert Opin Pharmacother. 2010 Jun;11(8):1387-402. PMID 20446853

[8] Adjei AA: Pemetrexed (Alimta): a novel multitargeted antifolate agent. Expert Rev Anticancer Ther. 2003 Apr;3(2):145-56. PMID 12722874

[9] Knox C, Law V, Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS (2011). „DrugBank 3.0: a comprehensive resource for omics research on drugs”. Nucleic Acids Res. 39 (Database issue): D1035-41. DOI:10.1093/nar/gkq1126. PMC 3013709. PMID 21059682. edit

[10] David S. Wishart, Craig Knox, An Chi Guo, Dean Cheng, Savita Shrivastava, Dan Tzur, Bijaya Gautam, and Murtaza Hassanali (2008). „DrugBank: a knowledgebase for drugs, drug actions and drug targets”. Nucleic Acids Res 36 (Database issue): D901-6. DOI:10.1093/nar/gkm958. PMC 2238889. PMID 18048412. edit

[11] McLeod, Howard L.; James Cassidy, Robert H. Powrie, David G. Priest, Mark A. Zorbas, Timothy W. Synold, Stephen Shibata, Darcy Spicer, Donald Bissett, Yazdi K. Pithavala, Mary A. Collier, Linda J. Paradiso, John D. Roberts (Jul 2000). „Pharmacokinetic and Pharmacodynamic Evaluation of the Glycinamide Ribonucleotide Formyltransferase Inhibitor AG2034”. Clinical Cancer Research 6 (7): 2677–84. PMID 10914709.

[12] Avendano, Carmen; Menendez, J. Carlos (April 2008). Medicinal Chemistry of Anticancer Drugs. Amsterdam: Elsevier. str. 37. ISBN 0-444-52824-5.

[13] Ghose, A.K., Viswanadhan V.N., and Wendoloski, J.J. (1998). „Prediction of Hydrophobic (Lipophilic) Properties of Small Organic Molecules Using Fragment Methods: An Analysis of AlogP and CLogP Methods”. J. Phys. Chem. A 102: 3762-3772. DOI:10.1021/jp980230o.

[14] Tetko IV, Tanchuk VY, Kasheva TN, Villa AE. (2001). „Estimation of Aqueous Solubility of Chemical Compounds Using E-State Indices”. Chem Inf. Comput. Sci. 41: 1488-1493. DOI:10.1021/ci000392t. PMID 11749573. edit

[15] Ertl P., Rohde B., Selzer P. (2000). „Fast calculation of molecular polar surface area as a sum of fragment based contributions and its application to the prediction of drug transport properties”. J. Med. Chem. 43: 3714-3717. DOI:10.1021/jm000942e. PMID 11020286. edit

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