Plinabulin

Plinabulin

Names
IUPAC name (3Z,6Z)-3-Benzylidene-6-{[5-(2-methyl-2-propanyl)-1H-imidazol-4-yl]methylene}-2,5-piperazinedione
Identifiers
CAS Number	714272-27-2
ChemSpider	8125252
Jmol interactive 3D	Image
PubChem	9949641
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- Key: UNRCMCRRFYFGFX-TYPNBTCFSA-N InChI=1/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- Key: UNRCMCRRFYFGFX-TYPNBTCFBU
SMILES O=C3/C(=C/c1ncnc1C(C)(C)C)NC(=O)C(=C\c2ccccc2)\N3
Properties
Chemical formula	C19H20N4O2
Molar mass	336.40 g·mol^−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Plinabulin (NPI-2358) is a 2,5-diketopiperazine derivative ^[1] that is being developed as an experimental cancer drug. It is a synthetic analog of the natural compound phenylahistin.^[2] Plinabulin interrupts tumor blood flow via disruption of the tumor's vascular endothelial cells resulting in tumor necrosis.^[3][4] It also has a tubulin-depolymerizing activity.^[5]

It has undergone Phase I and Phase II clinical trials for non-small cell lung cancer.^[6][7]

References

1. Borthwick AD (2012). "2,5-Diketopiperazines: Synthesis, Reactions, Medicinal Chemistry, and Bioactive Natural Products". Chemical Reviews 112 (7): 3641–3716. doi:10.1021/cr200398y. PMID 22575049.
2. Yamazaki, Yuri; Tanaka, Koji; Nicholson, Benjamin; Deyanat-Yazdi, Gordafaried; Potts, Barbara; Yoshida, Tomoko; Oda, Akiko; Kitagawa, Takayoshi; Orikasa, Sumie; Kiso, Yoshiaki (2012). "Synthesis and structure-activity relationship study of antimicrotubule agents phenylahistin derivatives with a didehydropiperazine-2,5-dione structure". Journal of Medicinal Chemistry 55 (3): 1056–1071. doi:10.1021/jm2009088. PMID 22185476.
3. Nicholson, Benjamin; Lloyd, G. Kenneth; Miller, Brian R.; Palladino, Michael A.; Kiso, Yoshiaki; Hayashi, Yoshio; Neuteboom, Saskia T. C. (2006). "NPI-2358 is a tubulin-depolymerizing agent: in-vitro evidence for activity as a tumor vascular-disrupting agent". Anti-Cancer Drugs 17 (1): 25–31. doi:10.1097/01.cad.0000182745.01612.8a. PMID 16317287.
4. Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, Anderson KC (2011). "A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells". Blood 117 (21): 5692–700. doi:10.1182/blood-2010-12-323857. PMC 3110026. PMID 21454451.
5. Hayashi Y, Yamazaki-Nakamura Y, Yakushiji F. "Medicinal chemistry and chemical biology of diketopiperazine-type antimicrotubule and vascular-disrupting agents." Chem Pharm Bull (Tokyo). 2013;61(9) 889-901. PMID 23995353
6. "NPI-2358". clinicaltrials.gov.
7. Monica M. Mita; et al. (2010). "Phase 1 First-in-Human Trial of the Vascular Disrupting Agent Plinabulin (NPI-2358) in Patients with Solid Tumors or Lymphomas". Clin Cancer Res 16 (23): 5892–5899. doi:10.1158/1078-0432.CCR-10-1096. PMID 21138873.