Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C37H38F3N3O8 |
| Molecular Weight | 709.7081 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[H][C@@]12CC3=C(C(O)=C(OC)C(C)=C3)[C@@]([H])(N1C)[C@]4([H])CC5=C([C@H](CNC(=O)\C=C\C6=CC(=CC=C6)C(F)(F)F)N4[C@H]2O)C7=C(OCO7)C(C)=C5OC(C)=O
InChI
InChIKey=VPAHZSUNBOYNQY-DLVGLDQCSA-N
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
PM-00104 (Zalypsis®) is a synthethic tetrahydroisoquinolone alkaloid, which is structurally similar to many marine organisms. PM-00104 is a DNA binding agent, causing inhibition of the cell cycle and transcription, which can lead to double stranded DNA breaks. Immunohistochemical studies in tumors also demonstrated histone-H2AX phosphorylation and p53 overexpression. PM-00104 has progressed into phase II clinical trials to treat Ewing sarcoma, urothelial carcinoma, multiple myeloma, endometrial and cervical cancer. The phase II study concluded that there were no objective responses in the cohort of 16 evaluable patients with Ewing sarcoma. The study of Urothelial carcinoma treatment was terminated early because there seemed to be no benefit from the current therapy. Moreover, PM-00104 as a single-agent did not prove to be an effective therapy for patients with advanced/metastatic endometrial or cervical cancer. None achieved objective tumor response was in phase II study for the treatment of advanced/metastatic endometrial or cervical cancer. Preliminary data showed PM-00104 to be safe to use in the treatment of multiple myeloma but the complete results from this trial have not been published.
Originator
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines. | 2009 Sep 9 |
|
| Characterization and analysis of human chordoma cell lines. | 2010 Jun 1 |
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| XPF-dependent DNA breaks and RNA polymerase II arrest induced by antitumor DNA interstrand crosslinking-mimetic alkaloids. | 2011 Aug 26 |
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| Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response. | 2011 May |
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| Temperature-induced melting of double-stranded DNA in the absence and presence of covalently bonded antitumour drugs: insight from molecular dynamics simulations. | 2011 Oct |
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| First-in-man phase I trial of two schedules of the novel synthetic tetrahydroisoquinoline alkaloid PM00104 (Zalypsis) in patients with advanced solid tumours. | 2012 Apr 10 |
|
| Population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients. | 2012 Jan |
|
| Population pharmacokinetic-pharmacodynamic analysis of neutropenia in cancer patients receiving PM00104 (Zalypsis(®)). | 2012 Nov |
|
| Phase II study of weekly PM00104 (ZALYPSIS(®)) in patients with pretreated advanced/metastatic endometrial or cervical cancer. | 2013 |
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| Phase I study of PM00104 (Zalypsis®) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors. | 2013 Jun |
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| A phase I pharmacokinetic study of PM00104 (Zalypsis) administered as a 24-h intravenous infusion every 3 weeks in patients with advanced solid tumors. | 2013 May |
|
| Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104). | 2013 Nov |
|
| Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway. | 2013 Oct |
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| Phase II clinical trial of PM00104 (Zalypsis(®)) in urothelial carcinoma patients progressing after first-line platinum-based regimen. | 2014 Apr |
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| Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis. | 2014 Apr 23 |
|
| Phase I study of carboplatin in combination with PM00104 (Zalypsis®) in patients with advanced solid tumors. | 2014 Aug |
|
| PM00104 (Zalypsis®): a marine derived alkylating agent. | 2014 Aug 15 |
|
| A Phase II multicenter, open-label, clinical and pharmokinetic trial of PM00104 in patients with advanced Ewing Family of Tumors. | 2014 Feb |
|
| Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia. | 2015 Nov 21 |
|
| Phase I/II study of weekly PM00104 (Zalypsis®) in patients with relapsed/refractory multiple myeloma. | 2016 Feb |
|
| Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone. | 2017 Jan |
Patents
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NCI_THESAURUS |
C2842
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DB12454
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16061448
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C21EZR41AY
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300000041343
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308359-57-1
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C62763
Created by
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PRIMARY | NCIT |
ACTIVE MOIETY
