Plinabulin (NPI-2358)

Modify Date: 2024-01-02 13:39:39

Plinabulin (NPI-2358) structure	Common Name	Plinabulin (NPI-2358)
	CAS Number	714272-27-2	Molecular Weight	336.388
	Density	1.3±0.1 g/cm3	Boiling Point	730.3±60.0 °C at 760 mmHg
	Molecular Formula	C₁₉H₂₀N₄O₂	Melting Point	N/A
	MSDS	N/A	Flash Point	395.5±32.9 °C

Use of Plinabulin (NPI-2358)

Plinabulin (NPI-2358) is a vascular disrupting agents (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells.IC50 Value: 9.8~18 nMTarget: Microtubule/Tubulinin 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. 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. in vivo: NPI-2358 (7.5 mg/kg) inhibits tumor growth in human plasmacytoma mouse xenograft models at well-tolerated doses. 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.

Name	(3Z,6Z)-3-benzylidene-6-[(5-tert-butyl-1H-imidazol-4-yl)methylidene]piperazine-2,5-dione
Synonym	More Synonyms

Description	Plinabulin (NPI-2358) is a vascular disrupting agents (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells.IC50 Value: 9.8~18 nMTarget: Microtubule/Tubulinin 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. 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. in vivo: NPI-2358 (7.5 mg/kg) inhibits tumor growth in human plasmacytoma mouse xenograft models at well-tolerated doses. 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.
Related Catalog	Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin Research Areas >> Cancer
References	[1]. Nicholson B et al. 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. [2]. Monica M. Mita et al. Phase 1 First-in-Human Trial of the Vascular Disrupting Agent Plinabulin (NPI-2358) in Patients with Solid Tumors or Lymphomas Clin Cancer Res December 1, 2010 16; 5892 [3]. Yakushiji F, Tanaka H, Muguruma K, Iwahashi T, Yamazaki Y, Hayashi Y.,Prodrug study of plinabulin using a click strategy focused on the effects of a replaceable water-solubilizing moiety.,Chem Pharm Bull (Tokyo). 2012;60(7):877-81. [4]. Yamazaki Y, Sumikura M, Masuda Y, Hayashi Y, Yasui H, Kiso Y, Chinen T, Usui T, Yakushiji F, Potts B, Neuteboom S, Palladino M, Lloyd GK, Hayashi Y.,Synthesis and structure-activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents.,Bioorg Med Chem. 2012 Jul 15;20(14):4279-89. Epub 2012 Jun 4. [5]. Bertelsen LB, Shen YY, Nielsen T, St?dkilde-J?rgensen H, Lloyd GK, Siemann DW, Horsman MR.,Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation.Int J Radiat Biol. 2011 Nov;87(11):1126-34.

Description

Related Catalog

Signaling Pathways >> Cell Cycle/DNA Damage >> Microtubule/Tubulin

Signaling Pathways >> Cytoskeleton >> Microtubule/Tubulin

Research Areas >> Cancer

References

[1]. Nicholson B et al. 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.

[2]. Monica M. Mita et al. Phase 1 First-in-Human Trial of the Vascular Disrupting Agent Plinabulin (NPI-2358) in Patients with Solid Tumors or Lymphomas Clin Cancer Res December 1, 2010 16; 5892

[3]. Yakushiji F, Tanaka H, Muguruma K, Iwahashi T, Yamazaki Y, Hayashi Y.,Prodrug study of plinabulin using a click strategy focused on the effects of a replaceable water-solubilizing moiety.,Chem Pharm Bull (Tokyo). 2012;60(7):877-81.

[4]. Yamazaki Y, Sumikura M, Masuda Y, Hayashi Y, Yasui H, Kiso Y, Chinen T, Usui T, Yakushiji F, Potts B, Neuteboom S, Palladino M, Lloyd GK, Hayashi Y.,Synthesis and structure-activity relationships of benzophenone-bearing diketopiperazine-type anti-microtubule agents.,Bioorg Med Chem. 2012 Jul 15;20(14):4279-89. Epub 2012 Jun 4.

[5]. Bertelsen LB, Shen YY, Nielsen T, St?dkilde-J?rgensen H, Lloyd GK, Siemann DW, Horsman MR.,Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation.Int J Radiat Biol. 2011 Nov;87(11):1126-34.

Density	1.3±0.1 g/cm3
Boiling Point	730.3±60.0 °C at 760 mmHg
Molecular Formula	C₁₉H₂₀N₄O₂
Molecular Weight	336.388
Flash Point	395.5±32.9 °C
Exact Mass	336.158630
PSA	94.92000
LogP	2.66
Vapour Pressure	0.0±2.4 mmHg at 25°C
Index of Refraction	1.657

Precursor 6
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CAS#:17094-34-7 ethyl 4,4,4-tri... CAS#:51721-22-3 5-(1,1-Dimethyl...
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