Plinabulin (NPI-2358)

Description

Description

Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells. Phase 2.

9.8~18 nM ^[1]

In vitro

NPI-2358 binds to the colchicine-binding site of 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]

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]

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

Plinabulin (NPI-2358)

Catalog No.S1176

Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells. Phase 2.

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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

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 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.

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT00322608	Completed	Cancer	Nereus Pharmaceuticals, Inc.	2006-04	Phase 1
NCT00630110	Completed	Cancer	Nereus Pharmaceuticals, Inc.	2008-02	Phase 1\|Phase 2

Solubility (25°C) *	In vitro	DMSO	67 mg/mL (199 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	<1 mg/mL (<1 mM)
* <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.