U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C41H44N4O10S
Molecular Weight 784.874
Optical Activity UNSPECIFIED
Defined Stereocenters 7 / 7
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LURBINECTEDIN

SMILES

[H][C@@]12[C@@H]3SC[C@]4(NCCC5=C4NC6=CC=C(OC)C=C56)C(=O)OC[C@H](N1[C@@H](O)[C@@H]7CC8=CC(C)=C(OC)C(O)=C8[C@H]2N7C)C9=C%10OCOC%10=C(C)C(OC(C)=O)=C39

InChI

InChIKey=YDDMIZRDDREKEP-HWTBNCOESA-N
InChI=1S/C41H44N4O10S/c1-17-11-20-12-25-39(48)45-26-14-52-40(49)41(38-22(9-10-42-41)23-13-21(50-5)7-8-24(23)43-38)15-56-37(31(45)30(44(25)4)27(20)32(47)33(17)51-6)29-28(26)36-35(53-16-54-36)18(2)34(29)55-19(3)46/h7-8,11,13,25-26,30-31,37,39,42-43,47-48H,9-10,12,14-16H2,1-6H3/t25-,26-,30+,31+,37+,39-,41+/m0/s1

HIDE SMILES / InChI
Lurbinectedin (PM-01183) - is a synthetic tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogue with potential antineoplastic activity. Lurbinectedin covalently binds to residues lying in the minor groove of DNA, which may result in delayed progression through S phase, cell cycle arrest in the G2/M phase and cell death. Lurbinectedin is a novel anticancer agent currently undergoing late-stage (Phase II /III) clinical evaluation in platinum-resistant ovarian, BRCA1/2-mutated breast and small-cell lung cancer. Lurbinectedin is structurally related to trabectedin and it inhibits active transcription and the DNA repair machinery in tumour cells.

CNS Activity

Curator's Comment: Low CNS and testicular penetration: Tissue distribution studies show lurbinectedin distribution that is greatest in the spleen, liver, lymph nodes, thyroid glands, lung, kidney and small intestine, and lowest in the CNS and testes.

Approval Year

Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
153.8 ng/mL
7 mg 1 times / 3 weeks multiple, intravenous
dose: 7 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
LURBINECTEDIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
532.6 ng × h/mL
7 mg 1 times / 3 weeks multiple, intravenous
dose: 7 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
LURBINECTEDIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
51.4 h
7 mg 1 times / 3 weeks multiple, intravenous
dose: 7 mg
route of administration: Intravenous
experiment type: MULTIPLE
co-administered:
LURBINECTEDIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Disc. AE: Peripheral neuropathy, Myelosuppression...
AEs leading to
discontinuation/dose reduction:
Peripheral neuropathy (>1)
Myelosuppression (>1)
Neutropenia (>3)
Hypoalbuminemia (>3)
Febrile neutropenia (>3)
Fatigue (>3)
Sources:
6.9 mg/m2 1 times / 3 weeks steady, intravenous
Highest studied dose
Dose: 6.9 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 6.9 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
4 mg/m2 1 times / 3 weeks steady, intravenous
MTD
Dose: 4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 4 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
DLT: Thrombocytopenia...
Dose limiting toxicities:
Thrombocytopenia (grade 4, 1 patient)
Sources: Page: p. 57
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
DLT: AST increased, Neutropenia...
Dose limiting toxicities:
AST increased (grade 4, 2 patients)
Neutropenia (grade 4, 2 patients)
Fatigue (grade 3, 2 patients)
Nausea (grade 2, 2 patients)
Vomiting (grade 2, 2 patients)
Diarrhea (grade 2, 2 patients)
Sources: Page: p. 57
AEs

AEs

AESignificanceDosePopulation
Myelosuppression >1
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Peripheral neuropathy >1
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Fatigue >3
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Febrile neutropenia >3
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Hypoalbuminemia >3
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Neutropenia >3
Disc. AE
3.2 mg/m2 1 times / 3 weeks steady, intravenous
Recommended
Dose: 3.2 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 3.2 mg/m2, 1 times / 3 weeks
Sources:
unhealthy, 60 years (range: 40 - 83 years)
n = 105
Health Status: unhealthy
Condition: small cell lung cancer
Age Group: 60 years (range: 40 - 83 years)
Sex: M+F
Population Size: 105
Sources:
Thrombocytopenia grade 4, 1 patient
DLT
4 mg/m2 1 times / 3 weeks steady, intravenous
MTD
Dose: 4 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 4 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
Diarrhea grade 2, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
Nausea grade 2, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
Vomiting grade 2, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
Fatigue grade 3, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
AST increased grade 4, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
Neutropenia grade 4, 2 patients
DLT
5 mg/m2 1 times / 3 weeks steady, intravenous
Studied dose
Dose: 5 mg/m2, 1 times / 3 weeks
Route: intravenous
Route: steady
Dose: 5 mg/m2, 1 times / 3 weeks
Sources: Page: p. 57
unhealthy
n = 31
Health Status: unhealthy
Condition: advanced solid tumors
Population Size: 31
Sources: Page: p. 57
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Phase II randomized study of PM01183 versus topotecan in patients with platinum-resistant/refractory advanced ovarian cancer.
2017 Jun 1
Patents

Sample Use Guides

Non-Small Cell Lung Cancer: 3.2 mg/m2 Lurbinectedin (PM01183), day 1, 1-hour intravenous, every three weeks
Route of Administration: Intravenous
48 hours’ treatment with lurbinectedin (0.3–10 nmol/L) inhibited the proliferation of the ovarian cancer cells of CCC origin in a dose-dependent manner.
Name Type Language
LURBINECTEDIN
INN   WHO-DD  
INN   USAN  
Official Name English
LURBINECTEDIN [MI]
Common Name English
PM1183
Code English
LURBINECTEDIN [USAN]
Common Name English
PM-1183
Code English
TRYPTAMICIDIN
Common Name English
Lurbinectedin [WHO-DD]
Common Name English
lurbinectedin [INN]
Common Name English
(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
Systematic Name English
PM-01183
Code English
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,1
Systematic Name English
ZEPSYRE
Brand Name English
PM01183
Code English
ZEPZELCA
Brand Name English
LURBINECTEDIN [ORANGE BOOK]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C25760
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
EU-Orphan Drug EU/3/19/2143
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
FDA ORPHAN DRUG 646018
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
NCI_THESAURUS C2115
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
FDA ORPHAN DRUG 376512
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
Code System Code Type Description
EPA CompTox
DTXSID30198065
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
DRUG BANK
DB12674
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
WIKIPEDIA
Lurbinectedin
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
NCI_THESAURUS
C82382
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
INN
9397
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
SMS_ID
100000175912
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
MERCK INDEX
M12217
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
USAN
GH-125
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
FDA UNII
2CN60TN6ZS
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
RXCUI
2374729
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
DAILYMED
2CN60TN6ZS
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
CAS
497871-47-3
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY
PUBCHEM
57327016
Created by admin on Thu Jul 06 07:57:35 UTC 2023 , Edited by admin on Thu Jul 06 07:57:35 UTC 2023
PRIMARY