Plinabulin

Summary

Plinabulin (CHEMBL1096380) is a phase-3 clinical-stage small-molecule microtubule-destabilising agent; indicated across 5 conditions including non-small cell lung carcinoma and neutropenia.

At a glance

• Status: Max clinical phase 3 (not approved)
• Modality: Small molecule
• Indications: 5 conditions
• Clinical trials: 12
• Chemistry: 336.4 Da · C19H20N4O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1096380
Name	Plinabulin
Type	Small molecule
Max phase	3
FDA approved	no
PubChem CID	9949641
ChEBI	CHEBI:177413
Molecular formula	C19H20N4O2
Molecular weight	336.4
InChIKey	UNRCMCRRFYFGFX-TYPNBTCFSA-N

SMILES: CC(C)(C)C1=C(N=CN1)/C=C\2/C(=O)N/C(=C\C3=CC=CC=C3)/C(=O)N2

IUPAC name: (3Z,6Z)-3-benzylidene-6-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]piperazine-2,5-dione

ChEBI definition: A member of the class of 2,5-diketopiperazines that is piperazine-2,5-dione substituted by benzylidene and (5-tert-butyl-1H-imidazol-4-yl)methylidene groups at positions 3 and 6, respectively. It is a vascular disrupting agent and a microtubule destabalising agent which was in clinical trials (now discontinued) for the treatment of non-small cell lung cancer.

Pharmacological roles (ChEBI): microtubule-destabilising agent, antineoplastic agent, apoptosis inducer, angiogenesis inhibitor.

Also known as: NPI-2358, Plinabulin, Plinabulina, Plinabuline, PLINABULIN, plinabulin

Parent form; salt/anhydrous children: CHEMBL4063810

Patent coverage: 261 distinct patent families (686 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Broader ChEMBL bioactivity targets: 9 (assay-derived). Sample: RAF proto-oncogene serine/threonine-protein kinase, Cyclin-dependent kinase 1/cyclin B1, Tubulin, Tubulin, Tyrosine-protein kinase Lyn, Cytochrome P450 1A2, Cytochrome P450 2C9, Cytochrome P450 2C19, Mitogen-activated protein kinase 10.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 16 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CYP2C9	6.28	IC50	530	nM	CHEMBL_ACT_18678846
P02550	6	Kd	1000	nM	CHEMBL_ACT_15097445
P02550	5.97	Kd	1060	nM	CHEMBL_ACT_10873036
P02550	5.97	Kd	1060	nM	CHEMBL_ACT_3289222
P02550	5.97	Kd	1060	nM	CHEMBL_ACT_5137317
CYP1A2	5.91	IC50	1240	nM	CHEMBL_ACT_18678848
P02550	5.75	IC50	1800	nM	CHEMBL_ACT_15097447
Q6B856	5.62	IC50	2400	nM	CHEMBL_ACT_16893201
Q6B856	5.5	Ki	3200	nM	CHEMBL_ACT_16894008
CYP2C19	5.37	IC50	4230	nM	CHEMBL_ACT_18678844
Q6B856	5.19	Kd	6400	nM	CHEMBL_ACT_16894002
P49187	5.17	IC50	6800	nM	CHEMBL_ACT_16893231
RAF1	5.05	IC50	8900	nM	CHEMBL_ACT_16893232
CDK1	5	IC50	10100	nM	CHEMBL_ACT_16893233
Q6B856	5	Kd	10000	nM	CHEMBL_ACT_16894003

Target pathways

No target-pathway data for this drug (no mapped target genes).

Indications & clinical

Indications

5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
non-small cell lung carcinoma	3	MONDO:0005233	EFO:0003060
neutropenia	3	MONDO:0001475	MONDO:0001475
small cell lung carcinoma	2	MONDO:0008433	EFO:0000702
plasma cell myeloma	2	MONDO:0009693	EFO:0001378
neoplasm	1	MONDO:0005070	MONDO:0004992

Clinical trials

Total trials: 12.

Phase distribution

Phase	Trials
PHASE1/PHASE2	4
PHASE3	3
PHASE2	3
PHASE1	2

Top trials by phase / activity

NCT	Phase	Status	Title
NCT07361484	PHASE3	NOT_YET_RECRUITING	Docetaxel Plus Plinabulin vs Docetaxel Plus Placebo in Advanced/Metastatic Non-Squamous NSCLC After PD-1/PD-L1 Therapy and Platinum Chemotherapy (DUBLIN-4)
NCT03102606	PHASE3	COMPLETED	Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 3
NCT03294577	PHASE3	UNKNOWN	Plinabulin vs. Pegfilgrastim in Prevention of TAC Induced Neutropenia
NCT05130827	PHASE2	ACTIVE_NOT_RECRUITING	Study of Plinabulin and Pegfilgrastim in People With Multiple Myeloma Undergoing an Autologous Hematopoietic Stem Cell Transplant (AHCT)
NCT00630110	PHASE1/PHASE2	COMPLETED	Phase 1/2 Study of Vascular Disrupting Agent NPI-2358 + Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer
NCT02846792	PHASE1/PHASE2	TERMINATED	Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer
NCT03575793	PHASE1/PHASE2	COMPLETED	A Phase I/II Study of Nivolumab, Ipilimumab and Plinabulin in Patients With Recurrent Small Cell Lung Cancer
NCT04227990	PHASE2	COMPLETED	Plinabulin iv Solution in Prevention of TAC Induced Neutropenia
NCT04345900	PHASE2	COMPLETED	Plinabulin vs. Pegfilgrastim in Patients With Solid Tumors Receiving Docetaxel Myelosuppressive Chemotherapy Phase 2
NCT04902040	PHASE1/PHASE2	TERMINATED	Plinabulin in Combination With Radiation/Immunotherapy in Patients With Select Advanced Cancers After Progression on PD-1 or PD-L1 Targeted Antibodies
NCT00322608	PHASE1	COMPLETED	Study of the Vascular Disrupting Agent NPI-2358 in Patients With Advanced Solid Tumors or Lymphoma
NCT02812667	PHASE1	COMPLETED	Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).