Details of the Drug

General Information of Drug (ID: DMEFRTZ)

Drug Name

Lurbinectedin

Synonyms

UNII-2CN60TN6ZS; 497871-47-3; 2CN60TN6ZS; Lurbinectedin [INN]; SCHEMBL16152477; DTXSID30198065; DB12674; CS-6323; HY-16293; J3.652.626B

Indication

Disease Entry	ICD 11	Status	REF
Small-cell lung cancer	2C25.Y	Approved	[1]
leukaemia	2A60-2B33	Phase 3	[2]
Ovarian cancer	2C73	Phase 3	[2]
Endometrial cancer	2C76	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[3]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

784.9

Topological Polar Surface Area (xlogp)

3.9

Rotatable Bond Count (rotbonds)

4

Hydrogen Bond Donor Count (hbonddonor)

4

Hydrogen Bond Acceptor Count (hbondacc)

14

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 551 mcgh/L [4]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 107 mcg/L [4]
Clearance: The total plasma clearance of drug is 11 L/h [4]
Elimination: Approximately 89% of a given dose is recovered in the feces (<0.2% unchanged) and 6% in the urine (1% unchanged) [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 51 hours [4]
Metabolism: The drug is metabolized via the CYP3A4 [4]
Vd: The volume of distribution (Vd) of drug is 504 L [4]

Chemical Identifiers

Formula: C41H44N4O10S
IUPAC Name: [(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-yl] acetate
Canonical SMILES: CC1=CC2=C([C@@H]3[C@@H]4[C@H]5C6=C(C(=C7C(=C6[C@@H](N4[C@H]([C@H](C2)N3C)O)COC(=O)[C@@]8(CS5)C9=C(CCN8)C2=C(N9)C=CC(=C2)OC)OCO7)C)OC(=O)C)C(=C1OC)O
InChI: 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
InChIKey: YDDMIZRDDREKEP-HWTBNCOESA-N

Cross-matching ID

PubChem CID: 57327016
CAS Number: 497871-47-3
DrugBank ID: DB12674
TTD ID: D0V6OA
ACDINA ID: D01230

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human Deoxyribonucleic acid (hDNA)	TTUTN1I	NOUNIPROTAC	Inhibitor	[1]
Human Deoxyribonucleic acid minor groove (hDNA min)	TTOVXHF	NOUNIPROTAC	Inhibitor	[1]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Lurbinectedin (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Lurbinectedin and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[19]
Ivosidenib	DM8S6T7	Moderate	Increased metabolism of Lurbinectedin caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[20]
Troleandomycin	DMUZNIG	Major	Decreased metabolism of Lurbinectedin caused by Troleandomycin mediated inhibition of CYP450 enzyme.	Bacterial infection [1A00-1C4Z]	[20]
Pexidartinib	DMS2J0Z	Major	Decreased metabolism of Lurbinectedin caused by Pexidartinib mediated inhibition of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[20]
Eslicarbazepine	DMZREFQ	Major	Decreased metabolism of Lurbinectedin caused by Eslicarbazepine mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[20]
Tazemetostat	DMWP1BH	Moderate	Increased metabolism of Lurbinectedin caused by Tazemetostat mediated induction of CYP450 enzyme.	Follicular lymphoma [2A80]	[20]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Lurbinectedin and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[21]
Tildrakizumab	DMLW9HG	Moderate	Additive myelosuppressive effects by the combination of Lurbinectedin and Tildrakizumab.	Psoriasis [EA90]	[22]
Risankizumab	DMM32GT	Moderate	Additive immunosuppressive effects by the combination of Lurbinectedin and Risankizumab.	Psoriasis [EA90]	[22]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Lurbinectedin caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[20]
Larotrectinib	DM26CQR	Moderate	Decreased metabolism of Lurbinectedin caused by Larotrectinib mediated inhibition of CYP450 enzyme.	Solid tumour/cancer [2A00-2F9Z]	[20]
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⏷ Show the Full List of 11 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Lactic acid	E00020	612	Acidulant
Saccharose	E00091	5988	Binding agent; Coating agent; Cryoprotectant; Diluent; Flavoring agent; Suspending agent; Viscosity-controlling agent
Sodium hydroxide	E00234	14798	Alkalizing agent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Lurbinectedin 4 mg Injection	4 mg	Injection	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	ClinicalTrials.gov (NCT02421588) Clinical Trial of Lurbinectedin (PM01183) in Platinum Resistant Ovarian Cancer Patients. U.S. National Institutes of Health.
3	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4	FDA Approved Drug Products: Zepzelca (lurbinectedin) for intravenous injection
5	Brostallicin (PNU-166196), a new minor groove DNA binder: preclinical and clinical activity. Expert Opin Investig Drugs. 2009 Dec;18(12):1939-46.
6	Defining GC-specificity in the minor groove: side-by-side binding of the di-imidazole lexitropsin to C-A-T-G-G-C-C-A-T-G. Structure. 1997 Aug 15;5(8):1033-46.
7	Structural studies of atom-specific anticancer drugs acting on DNA. Pharmacol Ther. 1999 Sep;83(3):181-215.
8	Drug-DNA binding specificity: binding of netropsin and distamycin to poly(d2NH2A-dT). Biopolymers. 1990;30(1-2):223-7.
9	Development of distamycin-related DNA binding anticancer drugs. Expert Opin Investig Drugs. 2001 Sep;10(9):1703-14.
10	Cisplatin and DNA repair in cancer chemotherapy.Trends Biochem Sci.1995 Oct;20(10):435-9.
11	Structures of oxaliplatin-oligonucleotide adducts from DNA.J Mass Spectrom.2012 Oct;47(10):1282-93.
12	31P NMR spectra of ethidium, quinacrine, and daunomycin complexes with poly(adenylic acid).poly(uridylic acid) RNA duplex and calf thymus DNA. Biochemistry. 1989 Apr 4;28(7):2804-12.
13	Pharmacokinetics and metabolism of ifosfamide in relation to DNA damage assessed by the COMET assay in children with cancer. Br J Cancer. 2005 May 9;92(9):1626-35.
14	O6-methylguanine-DNA methyltransferase activity and sensitivity to cyclophosphamide and cisplatin in human lung tumor xenografts. Int J Cancer. 1998 Sep 11;77(6):919-22.
15	Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer.Clin Cancer Res.2010 Oct 1;16(19):4899-905.
16	DNA intrastrand cross-link at the 5'-GA-3' sequence formed by busulfan and its role in the cytotoxic effect. Cancer Sci. 2004 May;95(5):454-8.
17	Brca2/Xrcc2 dependent HR, but not NHEJ, is required for protection against O(6)-methylguanine triggered apoptosis, DSBs and chromosomal aberrations... DNA Repair (Amst). 2009 Jan 1;8(1):72-86.
18	Predicting the myelotoxicity of chemotherapy: the use of pretreatment O6-methylguanine-DNA methyltransferase determination in peripheral blood mono... Melanoma Res. 2011 Dec;21(6):502-8.
19	Cerner Multum, Inc. "Australian Product Information.".
20	Product Information. Zepzelca (lurbinectedin). Jazz Pharmaceuticals, Palo Alto, CA.
21	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
22	Cerner Multum, Inc. "UK Summary of Product Characteristics.".