Page last updated: 2024-11-13

pm 01183

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

PM 01183: a covalent DNA minor groove binder and antineoplastic; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID57327016
CHEMBL ID4297516
SCHEMBL ID16152477
MeSH IDM0569086

Synonyms (44)

Synonym
S9603
lurbinectedin [usan:inn]
lurbinectedin ,
pm 01183
497871-47-3
unii-2cn60tn6zs
who 9397
pm01183
2cn60tn6zs ,
pm-1183
lurbinectedin [inn]
zepsyre
lurbinectedin [usan]
zepzelca
pm-01183
lurbinectedin [mi]
pm1183
spiro(6,16-(epithiopropanoxymethano)-7,13-imino-12h-1,3-dioxolo(7,8)isoquino(3,2-b)(3)benzazocine-20,1'-(1h)pyrido(3,4-b)indol)-19-one, 5-(acetyloxy)-2',3',4',6,6a,7,9',13,14,16-decahydro-8,14-dihydroxy-6',9-dimethoxy-4,10,23-trimethyl-, (1'r,6r,6ar,7r,13
lurbinectedin [orange book]
lurbinectedin [who-dd]
tryptamicidin
(1'r,6r,6ar,7r,13s,14s,16r)-8,14-dihydroxy-6',9-dimethoxy-4,10,23-trimethyl-19-oxo-2',3',4',6,7,9',12,13,14,16-decahydro-6ahspiro(7,13-azano-6,16-(epithiopropanooxymethano)(1,3)dioxolo(7,8)isoquinolino(3,2-b)(3)benzazocine-20,1'-pyrido(3,4-b)indol)-5-yl a
SCHEMBL16152477
DTXSID30198065 ,
CS-6323
HY-16293
DB12674
[(1r,2r,3r,11s,12s,14r,26r)-5,12-dihydroxy-6,6'-dimethoxy-7,21,30-trimethyl-27-oxospiro[17,19,28-trioxa-24-thia-13,30-diazaheptacyclo[12.9.6.13,11.02,13.04,9.015,23.016,20]triaconta-4(9),5,7,15,20,22-hexaene-26,1'-2,3,4,9-tetrahydropyrido[3,4-b]indole]-22
AT22223
Q27254568
CHEMBL4297516
EX-A4316
pm01183;pm-1183;ly-01017;ryptamicidin
MS-31432
gtpl10681
nsc-826275
nsc826275
EN300-23257233
(1r,2r,3r,11s,12s,14r,26r)-5,12-dihydroxy-6,6'-dimethoxy-7,21,30-trimethyl-27-oxo-2',3',4',9'-tetrahydro-17,19,28-trioxa-24-thia-13,30-diazaspiro[heptacyclo[12.9.6.1^{3,11}.0^{2,13}.0^{4,9}.0^{15,23}.0^{16,20}]triacontane-26,1'-pyrido[3,4-b]indole]-4(9),5
AKOS040741979
dtxcid60120556
lurbinectedina
lurbinectedinum
lurbinectedine

Research Excerpts

Toxicity

ExcerptReferenceRelevance
" Otherwise, adverse events mainly consisted of gastrointestinal manifestations (n = 11), febrile neutropenia/infections (n = 4), pulmonary toxicity (n = 2), and renal failure (n = 2)."( Safety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome.
Al-Kali, A; Alvarado, Y; Benton, CB; Chien, KS; Daver, N; Garcia-Manero, G; Hogan, WJ; Hornbaker, M; Jabbour, E; Jain, N; Kantarjian, H; Kwari, M; Maiti, A; Martinez, S; Pardanani, A; Pierce, S; Ravandi, F; Rodriguez, J; Santos, MA; Siguero, M; Tefferi, A; Zblewski, D, 2019
)
0.51

Pharmacokinetics

ExcerptReferenceRelevance
"The population-pharmacokinetic model indicated neither a dose nor time dependency, and no clinically meaningful pharmacokinetic differences were found when co-administered with other anticancer agents."( Population-Pharmacokinetic and Covariate Analysis of Lurbinectedin (PM01183), a New RNA Polymerase II Inhibitor, in Pooled Phase I/II Trials in Patients with Cancer.
Fernandez-Teruel, C; Fudio, S; Gonzalez, I; Lubomirov, R; Soto, A; Trocóniz, IF, 2019
)
0.51

Compound-Compound Interactions

ExcerptReferenceRelevance
"The objective of this study was to evaluate the antitumor effects of lurbinectedin as a single agent or in combination with existing anticancer agents for clear cell carcinoma (CCC) of the ovary, which is regarded as an aggressive, chemoresistant, histological subtype."( Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary.
Hashimoto, K; Kawano, M; Kimura, T; Kozasa, K; Kuroda, H; Mabuchi, S; Matsumoto, Y; Sasano, T; Sawada, K; Takahashi, R, 2016
)
0.43
"Lurbinectedin, a new agent that targets active transcription, exhibits antitumor activity in CCC when used as a single agent and has synergistic antitumor effects when combined with irinotecan."( Preclinical Investigations of PM01183 (Lurbinectedin) as a Single Agent or in Combination with Other Anticancer Agents for Clear Cell Carcinoma of the Ovary.
Hashimoto, K; Kawano, M; Kimura, T; Kozasa, K; Kuroda, H; Mabuchi, S; Matsumoto, Y; Sasano, T; Sawada, K; Takahashi, R, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
" While PM01183 and trabectedin appear functionally similar in cellular models, it is likely that the differences in pharmacokinetics may allow different dosing and scheduling of PM01183 in the clinic that could lead to novel and/or increased antitumor activity."( Trabectedin and its C subunit modified analogue PM01183 attenuate nucleotide excision repair and show activity toward platinum-resistant cells.
Escargueil, AE; Galmarini, CM; Henriques, JA; Larsen, AK; Machado, MS; Ouaret, D; Poindessous, V; Rocca, CJ; Sarasin, A; Soares, DG, 2011
)
0.37
" This phase I study evaluated an alternative lurbinectedin dosing schedule consisting of a 1-h infusion on days 1 and 8 every 3 weeks."( Phase I study of lurbinectedin, a synthetic tetrahydroisoquinoline that inhibits activated transcription, induces DNA single- and double-strand breaks, on a weekly × 2 every-3-week schedule.
Cullell-Young, M; Diamond, JR; Fernandez Teruel, C; Geary, D; Gore, L; Iglesias, JL; Jimeno, A; Ratain, MJ; Sharma, MR; Soto Matos-Pita, A; Szyldergemajn, S, 2017
)
0.46
" Absolute neutrophil count, platelet count, and lurbinectedin total plasma concentration were assessed in 244 patients treated with lurbinectedin with varied dosing schedules and doses."( Population Pharmacokinetic-Pharmacodynamic Modeling and Covariate Analyses of Neutropenia and Thrombocytopenia in Patients With Solid Tumors Treated With Lurbinectedin.
Fernández-Teruel, C; Fudio, S; Lubomirov, R, 2021
)
0.62
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
PPM1D proteinHomo sapiens (human)Potency0.05350.00529.466132.9993AID1347411
Interferon betaHomo sapiens (human)Potency0.05350.00339.158239.8107AID1347411
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (30)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (5)

Processvia Protein(s)Taxonomy
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (2)

Processvia Protein(s)Taxonomy
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (1)

Assay IDTitleYearJournalArticle
AID1347411qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Mechanism Interrogation Plate v5.0 (MIPE) Libary2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (72)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's0 (0.00)29.6817
2010's27 (37.50)24.3611
2020's45 (62.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 10.28

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index10.28 (24.57)
Research Supply Index4.51 (2.92)
Research Growth Index4.79 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (10.28)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials18 (25.00%)5.53%
Reviews6 (8.33%)6.00%
Case Studies4 (5.56%)4.05%
Observational0 (0.00%)0.25%
Other44 (61.11%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]