Plinabulin

Plinabulin (provisional name BPI-2358, formerly NPI-2358) is a small molecule under development by BeyondSpring Pharmaceuticals, and is in a world-wide Phase 3 clinical trial for non-small cell lung cancer.[1] Plinabulin is being investigated for the reduction of chemotherapy-induced neutropenia[2] and for anti-cancer effects in combination with immune checkpoint inhibitors[3][4] and in KRAS mutated tumors.[5]

Plinabulin
Names
IUPAC name
(3Z,6Z)-3-Benzylidene-6-{[5-(2-methyl-2-propanyl)-1H-imidazol-4-yl]methylene}-2,5-piperazinedione
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
UNII
  • 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
  • O=C3/C(=C/c1nc[nH]c1C(C)(C)C)NC(=O)C(=C\c2ccccc2)\N3
Properties
C19H20N4O2
Molar mass 336.395 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 blocks the polymerization of tubulin in a unique manner, resulting in multi-factorial effects including an enhanced immune-oncology response,[6] activation of the JNK pathway[7] and disruption of the tumor blood supply.

References
  1. "Assessment of Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC With at Least One Measurable Lung Lesion (DUBLIN-3)".
  2. Heist, R.S.; Aren, O.R.; Mita, A.C.; Polikoff, J.; Bazhenova, L.; Lloyd, G.K.; Mikrut, W.; Reich, W.; Spear, M.A.; Huang, L. (2014). Randomized Phase 2 Trial of Plinabulin (NPI-2358) Plus Docetaxel in Patients with Advanced Non-Small Lung Cancer (NSCLC). J Clin Oncol 32:5s.
  3. "Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer".
  4. Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC).
  5. Lloyd, G.K.; Du, L.; Lee, G.; Dalsing-Hernandez, J.; Kotlarczyk, K.; Gonzalez, K.; Nawrocki, S.; Carew, J.; Huang, L. (October 5–9, 2015). Activity of Plinabulin in Tumor Models with Kras Mutations. Proceedings of the International Conference on Molecular Targets and Cancer Therapeutics. Boston MA.
  6. Lloyd, G.K.; Muller, Ph.; Kashyap, A.; Zippelius, A.; Huang, L. (January 7–9, 2016). Plinabulin: Evidence for an Immune Mediated Mechanism of Action. Proceedings of the Meeting on the Function of Tumor Microenvironment in Cancer Progression. San Diego CA.
  7. Singh, A.V.; Bandi, M.; Raje, N.; Richardson, P.; Palladino, M.A.; Chauhan, D.; Anderson, K. (2011). "A Novel Vascular Disrupting Agent Plinabulin Triggers JNK-Mediated Apoptosis and Inhibits Angiogenesis in Multiple Myeloma Cells". Blood. 117 (21): 5692–5700. doi:10.1182/blood-2010-12-323857. PMC 3110026. PMID 21454451.
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