PLINABULIN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C19H20N4O2
Molecular Weight	336.3877
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	2
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)(C)C1=C(\C=C2/NC(=O)\C(NC2=O)=C\C3=CC=CC=C3)N=CN1

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28388240 | http://www.beyondspringpharma.com/en/plinabulin/ | https://www.ncbi.nlm.nih.gov/pubmed/21454451

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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16317287	Inhibitor 8297
Mitogen-activated protein kinase 8 3 Target ID: P45983\|\|\|Q308M2 Gene ID: 5599.0 Gene Symbol: MAPK8 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21454451	Activator 1430
Mitogen-activated protein kinase 9 4 Target ID: P45984\|\|\|Q15711 Gene ID: 5601.0 Gene Symbol: MAPK9 Target Organism: Homo sapiens (Human) Sources: https://www.ncbi.nlm.nih.gov/pubmed/21454451	Activator 1430

Conditions

Condition	Modality	Highest Phase	Product
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21327495	Primary	Phase III 656	Unknown Approved Use Unknown
Chemotherapy-induced neutropenia 1 Sources: https://clinicaltrials.gov/ct2/show/NCT03294577	Secondary	Phase II 1132	Unknown Approved Use Unknown
Multiple myeloma 159 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21454451	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/21138873 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: https://pubmed.ncbi.nlm.nih.gov/21138873 Page: p.5895	Sources: https://pubmed.ncbi.nlm.nih.gov/21138873 Page: p.5895

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C19 1478	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30119994/	no [IC50 >50 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30119994/	no [IC50 >50 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30119994/	yes [IC50 0.53 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30119994/	yes [IC50 1.24 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/30119994/	yes [IC50 4.23 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/16317287/	no

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific	X7519	https://aksci.com/item_detail.php?cat=X7519
BOC Sciences	714272-27-2	http://www.bocsci.com/description.asp?cas=714272-27-2
Chem Scene	CS-0506	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0506
ChemShuttle	108237	https://www.chemshuttle.com/catalogsearch/result/?q=108237
Excenen	EX-A292	http://www.excenen.com/searchresultlist.php?id=EX-A292
Lab Seeker	SC-96616	http://www.labseeker.com/search.php?keywords=SC-96616&category=0
LabSeeker	SC-96616	http://www.labseeker.com/search.php?keywords=SC-96616&category=0
Matrix Scientific	146070	http://www.matrixscientific.com/146070.html
MedChem Express	HY-14444	https://www.medchemexpress.com/search.html?q=HY-14444&ft=&fa=&fp=
MolPort	MolPort-009-679-475	https://www.molport.com/shop/molecule-link/MolPort-009-679-475
MolPort	MolPort-009-682-874	https://www.molport.com/shop/molecule-link/MolPort-009-682-874
eMolecules	44842447	https://orderbb.emolecules.com/search/#?query=44842447
eNovation Chemicals	D573006	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D573006&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3186396282	https://mcule.com/MCULE-3186396282/

PubMed

Title	Date	PubMed
NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent.	2006 Jan	16317287
Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel.	2012 Jun	21327495
Emerging treatment using tubulin inhibitors in advanced non-small cell lung cancer.	2017 May	28388240

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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).

Name

Type

Language

PLINABULIN

Official 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 [WHO-DD]

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