Zalypsis

    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 529911

CAS#: 308359-57-1

Description: Zalypsis, also known as PM-10450, is transcription factor inhibitor potentially for the treatment of lymphoma, and cervical carcinoma.


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Zalypsis is not in stock, may be available through custom synthesis. For cost-effective reason, minimum 1 gram order is requested. The product will be characterized by NMR, HPLC and MS analysis. Purity (HPLC) is usually >98%. CoA, QC data, MSDS will be provided when product is successfully made. The estimated lead time is 2-3 months. Please send email to sales@medkoo.com to inquire quote.


Chemical Structure

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Theoretical Analysis

MedKoo Cat#: 529911
Name: Zalypsis
CAS#: 308359-57-1
Chemical Formula: C37H38F3N3O8
Exact Mass: 709.26
Molecular Weight: 709.72
Elemental Analysis: C, 62.62; H, 5.40; F, 8.03; N, 5.92; O, 18.03


Synonym: PM-00104; PM-10450; PM00104; PM10450; PM 00104; PM 10450

IUPAC/Chemical Name: 2-Propenamide, N-(((6aS,7R,13S,14S,16R)-5-(acetyloxy)-6,6a,7,13,14,16-hexahydro-8,14-dihydroxy-9-methoxy-4,10,17-trimethyl-7,13-imino-12H-1,3-dioxolo(7,8)isoquino(3,2-b)(3)benzazocin-16-yl)methyl)-3-(3-(trifluoromethyl)phenyl)-, (2E)-

InChi Key: VPAHZSUNBOYNQY-DLVGLDQCSA-N

InChi Code: InChI=1S/C37H38F3N3O8/c1-17-11-21-13-25-36(47)43-24(30(42(25)4)28(21)31(46)32(17)48-5)14-23-29(35-34(49-16-50-35)18(2)33(23)51-19(3)44)26(43)15-41-27(45)10-9-20-7-6-8-22(12-20)37(38,39)40/h6-12,24-26,30,36,46-47H,13-16H2,1-5H3,(H,41,45)/b10-9+/t24-,25-,26-,30-,36-/m0/s1

SMILES Code: O=C(NC[C@H]1C2=C(C(OC(C)=O)=C(C)C3=C2OCO3)C[C@@]4([H])[C@@](N5C)([H])C6=C(O)C(OC)=C(C)C=C6C[C@@]5([H])[C@H](O)N41)/C=C/C7=CC=CC(C(F)(F)F)=C7


Technical Data

Appearance:
Solid powder

Purity:
>98% (or refer to the Certificate of Analysis)

Shipping Condition:
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition:
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility:
Soluble in DMSO

Shelf Life:
>2 years if stored properly

Drug Formulation:
This drug may be formulated in DMSO

Stock Solution Storage:
0 - 4 C for short term (days to weeks), or -20 C for long term (months).

Harmonized System Code:
293490


References

1: Moneo V, Serelde BG, Blanco-Aparicio C, Diaz-Uriarte R, Avilés P, Santamaría G, Tercero JC, Cuevas C, Carnero A. Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis. BMC Cancer. 2014 Apr 23;14:281. doi: 10.1186/1471-2407-14-281. PubMed PMID: 24758355; PubMed Central PMCID: PMC4023704.

2: Colado E, Paíno T, Maiso P, Ocio EM, Chen X, Alvarez-Fernández S, Gutiérrez NC, Martín-Sánchez J, Flores-Montero J, San Segundo L, Garayoa M, Fernández-Lázaro D, Vidriales MB, Galmarini CM, Avilés P, Cuevas C, Pandiella A, San-Miguel JF. Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response. Haematologica. 2011 May;96(5):687-95. doi: 10.3324/haematol.2010.036400. PubMed PMID: 21330323; PubMed Central PMCID: PMC3084915.

3: Romano M, Frapolli R, Zangarini M, Bello E, Porcu L, Galmarini CM, García-Fernández LF, Cuevas C, Allavena P, Erba E, D'Incalci M. Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104). Int J Cancer. 2013 Nov;133(9):2024-33. doi: 10.1002/ijc.28213. PubMed PMID: 23588839.

4: Leal JF, García-Hernández V, Moneo V, Domingo A, Bueren-Calabuig JA, Negri A, Gago F, Guillén-Navarro MJ, Avilés P, Cuevas C, García-Fernández LF, Galmarini CM. Molecular pharmacology and antitumor activity of Zalypsis in several human cancer cell lines. Biochem Pharmacol. 2009 Jul 15;78(2):162-70. doi: 10.1016/j.bcp.2009.04.003. PubMed PMID: 19427997.

5: Ocio EM, Maiso P, Chen X, Garayoa M, Alvarez-Fernández S, San-Segundo L, Vilanova D, López-Corral L, Montero JC, Hernández-Iglesias T, de Alava E, Galmarini C, Avilés P, Cuevas C, San-Miguel JF, Pandiella A. Zalypsis: a novel marine-derived compound with potent antimyeloma activity that reveals high sensitivity of malignant plasma cells to DNA double-strand breaks. Blood. 2009 Apr 16;113(16):3781-91. doi: 10.1182/blood-2008-09-177774. Erratum in: Blood. 2010 Jul 8;116(1):151. PubMed PMID: 19020308.

6: Petek BJ, Jones RL. PM00104 (Zalypsis®): a marine derived alkylating agent. Molecules. 2014 Aug 15;19(8):12328-35. doi: 10.3390/molecules190812328. Review. PubMed PMID: 25153860.

7: Ocio EM, Oriol A, Bladé J, Teruel AI, Martín J, de la Rubia J, Gutiérrez NC, Rodríguez Díaz-Pavón J, Martínez González S, Coronado C, Fernández-García EM, Siguero Gómez M, Fernández-Teruel C, San Miguel J. Phase I/II study of weekly PM00104 (Zalypsis®) in patients with relapsed/refractory multiple myeloma. Br J Haematol. 2016 Feb;172(4):625-8. doi: 10.1111/bjh.13515. PubMed PMID: 26033438.

8: Castellano DE, Bellmunt J, Maroto JP, Font-Pous A, Morales-Barrera R, Ghanem I, Suarez C, Martín Lorente C, Etxaniz O, Capdevila L, Coronado C, Alfaro V, Siguero M, Fernández-Teruel C, Carles J. Phase II clinical trial of PM00104 (Zalypsis(®)) in urothelial carcinoma patients progressing after first-line platinum-based regimen. Cancer Chemother Pharmacol. 2014 Apr;73(4):857-67. doi: 10.1007/s00280-014-2419-7. PubMed PMID: 24570330.

9: Massard C, Margetts J, Amellal N, Drew Y, Bahleda R, Stephens P, Armand JP, Calvert H, Soria JC, Coronado C, Kahatt C, Alfaro V, Siguero M, Fernández-Teruel C, Plummer R. Phase I study of PM00104 (Zalypsis®) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors. Invest New Drugs. 2013 Jun;31(3):623-30. doi: 10.1007/s10637-012-9843-5. Erratum in: Invest New Drugs. 2013 Jun;31(3):799. Stevens, Peter [corrected to Stephens, Peter]. PubMed PMID: 22688291.

10: Capdevila J, Clive S, Casado E, Michie C, Piera A, Sicart E, Carreras MJ, Coronado C, Kahatt C, Soto Matos-Pita A, Fernandez Teruel C, Siguero M, Cullell-Young M, Tabernero J. A phase I pharmacokinetic study of PM00104 (Zalypsis) administered as a 24-h intravenous infusion every 3 weeks in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2013 May;71(5):1247-54. doi: 10.1007/s00280-013-2119-8. PubMed PMID: 23455428.

11: Martin LP, Krasner C, Rutledge T, Ibañes ML, Fernández-García EM, Kahatt C, Gómez MS, McMeekin S. Phase II study of weekly PM00104 (ZALYPSIS(®)) in patients with pretreated advanced/metastatic endometrial or cervical cancer. Med Oncol. 2013;30(3):627. doi: 10.1007/s12032-013-0627-3. PubMed PMID: 23771800.

12: Salazar R, Calles A, Gil M, Durán I, García M, Hidalgo M, Coronado C, Alfaro V, Siguero M, Fernández-Teruel C, Prados R, Calvo E. Phase I study of carboplatin in combination with PM00104 (Zalypsis®) in patients with advanced solid tumors. Invest New Drugs. 2014 Aug;32(4):644-52. doi: 10.1007/s10637-014-0072-y. PubMed PMID: 24535315.

13: González-Sales M, Valenzuela B, Pérez-Ruixo C, Fernández Teruel C, Miguel-Lillo B, Soto-Matos A, Pérez-Ruixo JJ. Population pharmacokinetic-pharmacodynamic analysis of neutropenia in cancer patients receiving PM00104 (Zalypsis(®)). Clin Pharmacokinet. 2012 Nov;51(11):751-64. doi: 10.1007/s40262-012-0011-z. PubMed PMID: 23055348.

14: Pérez-Ruixo C, Valenzuela B, Fernández Teruel C, González-Sales M, Miguel-Lillo B, Soto-Matos A, Pérez-Ruixo JJ. Population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients. Cancer Chemother Pharmacol. 2012 Jan;69(1):15-24. doi: 10.1007/s00280-011-1644-6. PubMed PMID: 21590449.

15: Yap TA, Cortes-Funes H, Shaw H, Rodriguez R, Olmos D, Lal R, Fong PC, Tan DS, Harris D, Capdevila J, Coronado C, Alfaro V, Soto-Matos A, Fernández-Teruel C, Siguero M, Tabernero JM, Paz-Ares L, de Bono JS, López-Martin JA. First-in-man phase I trial of two schedules of the novel synthetic tetrahydroisoquinoline alkaloid PM00104 (Zalypsis) in patients with advanced solid tumours. Br J Cancer. 2012 Apr 10;106(8):1379-85. doi: 10.1038/bjc.2012.99. PubMed PMID: 22491421; PubMed Central PMCID: PMC3326684.

16: Duan Z, Choy E, Harmon D, Yang C, Ryu K, Schwab J, Mankin H, Hornicek FJ. ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines. PLoS One. 2009 Sep 9;4(9):e6967. doi: 10.1371/journal.pone.0006967. PubMed PMID: 19742314; PubMed Central PMCID: PMC2734182.

17: Guirouilh-Barbat J, Antony S, Pommier Y. Zalypsis (PM00104) is a potent inducer of gamma-H2AX foci and reveals the importance of the C ring of trabectedin for transcription-coupled repair inhibition. Mol Cancer Ther. 2009 Jul;8(7):2007-14. doi: 10.1158/1535-7163.MCT-09-0336. PubMed PMID: 19584237.

18: López-Iglesias AA, González-Méndez L, San-Segundo L, Herrero AB, Hernández-García S, Martín-Sánchez M, Gutiérrez NC, Paíno T, Avilés P, Mateos MV, San-Miguel JF, Garayoa M, Ocio EM. Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone. Haematologica. 2017 Jan;102(1):168-175. doi: 10.3324/haematol.2016.146076. PubMed PMID: 27540138; PubMed Central PMCID: PMC5210247.

19: Martínez S, Pérez L, Galmarini CM, Aracil M, Tercero JC, Gago F, Albella B, Bueren JA. Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway. Br J Pharmacol. 2013 Oct;170(4):871-82. doi: 10.1111/bph.12331. PubMed PMID: 23937566; PubMed Central PMCID: PMC3799600.

20: Feuerhahn S, Giraudon C, Martínez-Díez M, Bueren-Calabuig JA, Galmarini CM, Gago F, Egly JM. XPF-dependent DNA breaks and RNA polymerase II arrest induced by antitumor DNA interstrand crosslinking-mimetic alkaloids. Chem Biol. 2011 Aug 26;18(8):988-99. doi: 10.1016/j.chembiol.2011.06.007. PubMed PMID: 21867914.