Plinabulin

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Plinabulin
Accession Number
DB05992
Type
Small Molecule
Groups
Investigational
Description
Not Available
Structure
Thumb
Synonyms
Not Available
External IDs
NPI-2358
Categories
UNII
986FY7F8XR
CAS number
714272-27-2
Weight
Average: 336.395
Monoisotopic: 336.1586259
Chemical Formula
C19H20N4O2
InChI Key
UNRCMCRRFYFGFX-TYPNBTCFSA-N
InChI
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-
IUPAC Name
(3Z,6Z)-3-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]-6-(phenylmethylidene)piperazine-2,5-dione
SMILES
CC(C)(C)C1=C(\C=C2/NC(=O)\C(NC2=O)=C\C2=CC=CC=C2)N=CN1

Pharmacology

Indication

Investigated for use/treatment in cancer/tumors (unspecified).

Pharmacodynamics
Not Available
Mechanism of action

NPI-2358 is a vascular disrupting agent currently in clinical development for the treatment of cancer by Nereus. NPI-2358 is one of over 200 synthetic analogues that were prepared following the discovery of the compound Halimide isolated from a marine fungus. In preclinical models of cancer, including lung, breast, sarcoma, colon and prostate, NPI-2358 demonstrated potent and selective anti-tumor effects in combination with docetaxel and other oncology therapies, as well as single-agent efficacy in a number of orthotopic models. NPI-2358 interacts with soluble beta-tubulin and prevents the polymerization of tubulin without altering dynamic microtubule function of formed microtubules. As demonstrated in preclinical testing, this target profile results in a highly specific nanomolar cytotoxicity while reducing the side effects seen in first-generation VDAs due to cardiotoxicity, hemodynamic changes and neuropathies.

TargetActionsOrganism
UTumor necrosis factorNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Nicholson B, Lloyd GK, Miller BR, Palladino MA, Kiso Y, Hayashi Y, Neuteboom ST: NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent. Anticancer Drugs. 2006 Jan;17(1):25-31. [PubMed:16317287]
External Links
ChemSpider
8125252
BindingDB
50030765
ChEMBL
CHEMBL1096380
HET
PN6
Wikipedia
Plinabulin
PDB Entries
5c8y / 5xi5

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentMalignancies1
1, 2CompletedTreatmentMalignancies1
1, 2RecruitingTreatmentLung Cancer Small Cell Lung Cancer (SCLC) / Lung Cancers1
1, 2TerminatedTreatmentALK Gene Translocation / EGFR Activating Mutation / Recurrent Non-Small Cell Lung Carcinoma / ROS1 Gene Translocation / Stage IIIb Non-small Cell Lung Cancer / Stage IIIB Non-Small Cell Lung Cancer AJCC v7 / Stage IV Non-Small Cell Lung Cancer / Stage IV Non-Small Cell Lung Cancer AJCC v71
2, 3Active Not RecruitingSupportive CareChemotherapy Induced Neutropenia2
3RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0218 mg/mLALOGPS
logP3.12ALOGPS
logP1.81ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)7.05ChemAxon
pKa (Strongest Basic)6.23ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area86.88 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity98.02 m3·mol-1ChemAxon
Polarizability37.16 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Tumor necrosis factor receptor binding
Specific Function
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da

Drug created on November 18, 2007 11:29 / Updated on June 04, 2019 06:20