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Details

Stereochemistry ACHIRAL
Molecular Formula C19H20N4O2
Molecular Weight 336.3884
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of PLINABULIN

SMILES

CC(C)(C)c1c(/C(/[H])=c\2/c(n/c(=C(/[H])\c3ccccc3)/c(n2)O)O)nc[nH]1

InChI

InChIKey=UNRCMCRRFYFGFX-TYPNBTCFSA-N
InChI=1S/C19H20N4O2/c1-19(2,3)16-13(20-11-21-16)10-15-18(25)22-14(17(24)23-15)9-12-7-5-4-6-8-12/h4-11H,1-3H3,(H,20,21)(H,22,25)(H,23,24)/b14-9-,15-10-

HIDE SMILES / InChI

Molecular Formula C19H20N4O2
Molecular Weight 336.3884
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 2
Optical Activity NONE

Plinabulin (formerly known as NPI-2358) is a potent microtubule-destabilizing agent that exerts its effect by binding to the colchicine-binding site of tubulin. Plinabulin projects its potent antitumor activity against a broad spectrum of tumor cell lines. This drug in combination with docetaxel is under development by BeyondSpring Pharmaceuticals in a worldwide Phase 3 clinical trial for non-small cell lung cancer. Pegfilgrastim is also in phase II clinical trial for the prevention of chemotherapy-induced neutropenia, where docetaxel, doxorubicin, and cyclophosphamide (TAC) were used as the chemotherapy. Plinabulin also possessed antitumor activity in animal models with multiple myeloma cancer cells, where the JNK protein appeared to be a primary target of plinabulin.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: P45983|||Q308M2
Gene ID: 5599.0
Gene Symbol: MAPK8
Target Organism: Homo sapiens (Human)
Target ID: P45984|||Q15711
Gene ID: 5601.0
Gene Symbol: MAPK9
Target Organism: Homo sapiens (Human)
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Secondary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse events​
30 mg/m2 1 times / week multiple, intravenous
RP2D
Dose: 30 mg/m2, 1 times / week
Route: intravenous
Route: multiple
Dose: 30 mg/m2, 1 times / week
Sources: Page: p.5895
unhealthy, ADULT
n = 18
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 18
Sources: Page: p.5895
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
PubMed

PubMed

TitleDatePubMed
NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent.
2006 Jan
Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel.
2012 Jun
Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer.
2017 May
Patents

Sample Use Guides

Docetaxel + Plinabulin (DP): on days 1 and 8 of the 21 day cycle, patients will receive plinabulin (P) administered via IV infusion over 30 minutes. On Day 1, the infusion begins 2 hours from the starting time of docetaxel infusion, i.e, approximately 60 minutes from the end of docetaxel infusion. On day 8, plinabulin infusion will be repeated. On Day 1, no pre-medication will be routinely administered for plinabulin infusion. Anti-emetics may be prescribed as indicated according to institutional guidelines for chemotherapy. On Day 8, antiemetic prophylaxis may be administered prior to plinabulin infusion.
Route of Administration: Intravenous
Human multiple myeloma (MM) cell lines MM.1S, MM.1R (Dex-resistant), RPMI-8226, and INA-6 (IL-6–dependent) were treated with plinabulin at different concentrations (range, 1nM to 10μM) for 24, 48, and 72 hours, and cell viability was measured by MTT assays. As a result, plinabulin significantly decreased the viability of all the MM cell lines in a time- and dose-dependent manner (IC50 ranges from 8nM to 10nM for different cell lines).
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:28:14 UTC 2021
Edited
by admin
on Fri Jun 25 21:28:14 UTC 2021
Record UNII
986FY7F8XR
Record Status Validated (UNII)
Record Version
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Name Type Language
PLINABULIN
INN   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
PLINABULIN [WHO-DD]
Common Name English
(3Z,6Z)-6-BENZYLIDENE-3-((5-(1,1-DIMETHYLETHYL)-1H-IMIDAZOL-4- YL)METHYLIDENE)PIPERAZINE-2,5-DIONE
Systematic Name English
PLINABULIN [INN]
Common Name English
PLINABULIN [MI]
Common Name English
NPI-2358
Code English
2,5-PIPERAZINEDIONE, 3-((5-(1,1-DIMETHYLETHYL)-1H-IMIDAZOL-4-YL)METHYLENE)-6-(PHENYLMETHYLENE)-, (3Z,6Z)-
Systematic Name English
PLINABULIN [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C67421
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
Code System Code Type Description
PUBCHEM
9949641
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
FDA UNII
986FY7F8XR
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
DRUG BANK
DB05992
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
INN
9206
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
ChEMBL
CHEMBL1096380
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
WIKIPEDIA
PLINABULIN
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
NCI_THESAURUS
C62444
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
MERCK INDEX
M8924
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY Merck Index
CAS
714272-27-2
Created by admin on Fri Jun 25 21:28:14 UTC 2021 , Edited by admin on Fri Jun 25 21:28:14 UTC 2021
PRIMARY
Related Record Type Details
TARGET->INHIBITOR OF AGGREGATION
Related Record Type Details
ACTIVE MOIETY