Plinabulin

Catalog No.S1176 Batch:S117601

Technical Data

Formula	C₁₉H₂₀N₄O₂
Molecular Weight	336.39	CAS No.	714272-27-2
Solubility (25°C)*	In vitro	DMSO	54 mg/mL (160.52 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Plinabulin is a vascular disrupting agent (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells. Phase 1/2.

Targets

Tubulin ^[1]

9.8 nM-18 nM

In vitro

NPI-2358 binds to the tubulin and has potent inhibitory to human tumor cell lines which have overexpressed Pgp or reduced nuclear Topo II catalytic activity, with IC50 from 9.8 to 18 nM. NPI-2358 is able to rapidly induce tubulin depolymerization in HUVECs and monolayer permeability even at 20 nM. ^[1] NPI-2358 induces cell death in MM cells with IC50 of 8-10 nM, which due to trigger early mitotic arrest in MM cells. NPI-2358 also inhibits tubule formation and migration of endothelial as well as MM cells, which leads to disrupt tumor vasculature. NPI-2358 could induces cell death in patient MM (CD138+) cells without effecting viability of normal mononuclear cells. Blockade of JNK abrogates NPI-2358-induced mitotic arrest or MM cell death. ^[2]

In vivo

NPI-2358 (7.5 mg/kg) inhibits tumor growth in human plasmacytoma mouse xenograft models at well-tolerated doses. ^[2] NPI-2358 induces a time- and dose-dependent decrease in tumour perfusion. NPI-2358 is more sensitive to the KHT sarcoma than the C3H tumour, while radiation response could enhance the antitumor activity in both models. ^[3]

Features

Synthetic analog of NPI-2350 and greater potentcy than NPI-2350.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines HT-29, PC-3, DU 145, MDA-MB-231, NCI-H292, Jurkat, MES-SA, MES-SA/Dx5, HL-60, HL-60/MX2. Concentrations 2 pM - 20 μM Incubation Time 24 hours. Method The adherent cells are plated in 96-well flat-bottomed plates and allowed to attach for 24 hours at 37 °C. HL-60 and HL-60/MX2 cells are plated in 96-well plates on the day of NPI-2358 addition. Serially diluted NPI-2358 is added to cells at concentrations ranging from 2 pM to 20 μM. Cells treated with a final concentration of 0.25% (v/v) DMSO serves as the vehicle control. Cell viability is assessed 48 hours later by measuring the reduction of resazurin with a fluorimeter. The IC50 value is calculated.
Animal Study:^{^[3]}	Animal Models CDF1 mice or C3H/Hej mice. Dosages ~15 mg/kg. Administration Injected intraperitoneally (i.p.) in a volume of 0.02 mL/g mouse body weight in CDF1 mice and 0.01 mL/g body weight for C3H/Hej mice.

Cell Assay:^{^[1]}

Cell lines
HT-29, PC-3, DU 145, MDA-MB-231, NCI-H292, Jurkat, MES-SA, MES-SA/Dx5, HL-60, HL-60/MX2.
Concentrations
2 pM - 20 μM
Incubation Time
24 hours.
Method
The adherent cells are plated in 96-well flat-bottomed plates and allowed to attach for 24 hours at 37 °C. HL-60 and HL-60/MX2 cells are plated in 96-well plates on the day of NPI-2358 addition. Serially diluted NPI-2358 is added to cells at concentrations ranging from 2 pM to 20 μM. Cells treated with a final concentration of 0.25% (v/v) DMSO serves as the vehicle control. Cell viability is assessed 48 hours later by measuring the reduction of resazurin with a fluorimeter. The IC50 value is calculated.

Animal Study:^{^[3]}

Animal Models
CDF1 mice or C3H/Hej mice.
Dosages
~15 mg/kg.
Administration
Injected intraperitoneally (i.p.) in a volume of 0.02 mL/g mouse body weight in CDF1 mice and 0.01 mL/g body weight for C3H/Hej mice.

References

Selleck's Plinabulin has been cited by 5 publications

Small Molecules Promote Selective Denaturation and Degradation of Tubulin Heterodimers through a Low-Barrier Hydrogen Bond [ J Med Chem, 2022, 65(13):9159-9173]	PubMed: 35762925
In Vitro Identification of Potential Metabolites of Plinabulin (NPI 2358) in Hepatic Preparations Using Liquid Chromatography-Ion Trap Mass Spectrometry [ ACS Omega, 2022, 7(25):21465-21472]	PubMed: 35785266
Covalent modification of Cys-239 in β-tubulin by small molecules as a strategy to promote tubulin heterodimer degradation. [ J Biol Chem, 2019, 294(20):8161-8170]	PubMed: 30940730
The Natural Compound Withaferin A Covalently Binds to Cys239 of β-Tubulin to Promote Tubulin Degradation. [ Mol Pharmacol, 2019, 96(6):711-719]	PubMed: 31585985
Multiplexing high-content flow (HCF) and quantitative high-throughput screening (qHTS) to identify compounds capable of decreasing cell viability, activating caspase 3/7, expressing annexin V, and changing mitochondrial membrane integrity. [Mathews LA Curr Protoc Chem Biol, 2013, 5(3):195-212]	PubMed: 24391083

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SHIPPING AND STORAGE
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