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
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
Molecular Formula | C41H44N4O10S |
Molecular Weight | 784.874 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 7 / 7 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
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.
Approval Year
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
153.8 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24563480 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
532.6 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24563480 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
51.4 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/24563480 |
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
Dose | Population | Adverse 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) Sources: Myelosuppression (>1) Neutropenia (>3) Hypoalbuminemia (>3) Febrile neutropenia (>3) Fatigue (>3) |
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 Health Status: unhealthy Sources: Page: p. 57 |
|
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) Sources: Page: p. 57Neutropenia (grade 4, 2 patients) Fatigue (grade 3, 2 patients) Nausea (grade 2, 2 patients) Vomiting (grade 2, 2 patients) Diarrhea (grade 2, 2 patients) |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
yes | ||||
yes | ||||
yes | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | ||||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
Page: 11.0 |
no | |||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sample Use Guides
In Vivo Use Guide
Sources: https://clinicaltrials.gov/ct2/show/NCT01951157
Non-Small Cell Lung Cancer: 3.2 mg/m2 Lurbinectedin (PM01183), day 1, 1-hour intravenous, every three weeks
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26986199
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.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 01:40:27 GMT 2023
by
admin
on
Sat Dec 16 01:40:27 GMT 2023
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Record UNII |
2CN60TN6ZS
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Record Status |
Validated (UNII)
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Record Version |
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-
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Official Name | English | ||
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Code | English | ||
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Common Name | English |
Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C25760
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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EU-Orphan Drug |
EU/3/19/2143
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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FDA ORPHAN DRUG |
646018
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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NCI_THESAURUS |
C2115
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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FDA ORPHAN DRUG |
376512
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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Code System | Code | Type | Description | ||
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DTXSID30198065
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DB12674
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admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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Lurbinectedin
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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PRIMARY | |||
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C82382
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9397
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100000175912
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m12217
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GH-125
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2CN60TN6ZS
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admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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2374729
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2CN60TN6ZS
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497871-47-3
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57327016
Created by
admin on Sat Dec 16 01:40:27 GMT 2023 , Edited by admin on Sat Dec 16 01:40:27 GMT 2023
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Related Record | Type | Details | ||
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EXCRETED UNCHANGED |
FECAL
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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EXCRETED UNCHANGED |
URINE
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BINDER->LIGAND |
BINDING
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Related Record | Type | Details | ||
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METABOLITE -> PARENT |
MAJOR
FECAL; PLASMA; URINE
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METABOLITE -> PARENT |
MAJOR
FECAL; PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Biological Half-life | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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AT STEADY-STATE |
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