PM-00104

Investigational

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

Structure Search

SMILES

COC1=C(C)C=C2C[C@H]3[C@H](O)N4[C@@H](CC5=C(OC(C)=O)C(C)=C6OCOC6=C5[C@@H]4CNC(=O)\C=C\C7=CC(=CC=C7)C(F)(F)F)[C@H](N3C)C2=C1O

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

HIDE SMILES / InChI

Molecular Formula	C37H38F3N3O8
Molecular Weight	709.7081
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	1
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25153860 | https://www.ncbi.nlm.nih.gov/pubmed/23771800 | https://www.ncbi.nlm.nih.gov/pubmed/19020308 | https://adisinsight.springer.com/drugs/800021558

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
Synergistic DNA-damaging effect in multiple myeloma with the combination of zalypsis, bortezomib and dexamethasone.	2017-01	27540138
Phase I/II study of weekly PM00104 (Zalypsis®) in patients with relapsed/refractory multiple myeloma.	2016-02	26033438
Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.	2015-11-21	26343861
PM00104 (Zalypsis®): a marine derived alkylating agent.	2014-08-15	25153860
Phase I study of carboplatin in combination with PM00104 (Zalypsis®) in patients with advanced solid tumors.	2014-08	24535315
Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.	2014-04-23	24758355
Phase II clinical trial of PM00104 (Zalypsis(®)) in urothelial carcinoma patients progressing after first-line platinum-based regimen.	2014-04	24570330
A Phase II multicenter, open-label, clinical and pharmokinetic trial of PM00104 in patients with advanced Ewing Family of Tumors.	2014-02	24173965
Comparison of in vitro and in vivo biological effects of trabectedin, lurbinectedin (PM01183) and Zalypsis® (PM00104).	2013-11	23588839
Inhibitory effects of marine-derived DNA-binding anti-tumour tetrahydroisoquinolines on the Fanconi anaemia pathway.	2013-10	23937566
Phase I study of PM00104 (Zalypsis®) administered as a 1-hour weekly infusion resting every fourth week in patients with advanced solid tumors.	2013-06	22688291
A phase I pharmacokinetic study of PM00104 (Zalypsis) administered as a 24-h intravenous infusion every 3 weeks in patients with advanced solid tumors.	2013-05	23455428
Phase II study of weekly PM00104 (ZALYPSIS(®)) in patients with pretreated advanced/metastatic endometrial or cervical cancer.	2013	23771800
Population pharmacokinetic-pharmacodynamic analysis of neutropenia in cancer patients receiving PM00104 (Zalypsis(®)).	2012-11	23055348
First-in-man phase I trial of two schedules of the novel synthetic tetrahydroisoquinoline alkaloid PM00104 (Zalypsis) in patients with advanced solid tumours.	2012-04-10	22491421
Population pharmacokinetics of PM00104 (Zalypsis(®)) in cancer patients.	2012-01	21590449
Temperature-induced melting of double-stranded DNA in the absence and presence of covalently bonded antitumour drugs: insight from molecular dynamics simulations.	2011-10	21727089
XPF-dependent DNA breaks and RNA polymerase II arrest induced by antitumor DNA interstrand crosslinking-mimetic alkaloids.	2011-08-26	21867914
Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response.	2011-05	21330323
Characterization and analysis of human chordoma cell lines.	2010-06-01	20461036
ZNF93 increases resistance to ET-743 (Trabectedin; Yondelis) and PM00104 (Zalypsis) in human cancer cell lines.	2009-09-09	19742314

Patents

Sample Use Guides

In Vivo Use Guide

2 mg/m(2) days 1, 8 and 15 every 4 weeks

Route of Administration: Intravenous

Substance Class	Chemical Created by `admin` on `Mon Mar 31 22:05:53 GMT 2025` Edited by `admin` on `Mon Mar 31 22:05:53 GMT 2025`
Record UNII	C21EZR41AY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

PM00104

Preferred Name

English

PM-00104

Common Name

English

ZALYPSIS

Brand Name

English

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)-

Systematic Name

English

PM00104 [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C2842