Plinabulin (provisional name BPI-2358, formerly NPI-2358) is a small molecule under development by BeyondSpring Pharmaceuticals, and has completed 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]
Quick Facts Names, Identifiers ...
Plinabulin
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| IUPAC name
(3Z,6Z)-3-Benzylidene-6-{[5-(2-methyl-2-propanyl)-1H-imidazol-4-yl]methylene}-2,5-piperazinedione |
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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
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O=C3/C(=C/c1nc[nH]c1C(C)(C)C)NC(=O)C(=C\c2ccccc2)\N3
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| Properties |
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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). |
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Plinabulin blocks the polymerization of tubulin in a unique manner, resulting in multi-factorial effects including an enhanced immune-oncology response,[6][7][8] activation of the JNK pathway[9] and disruption of the tumor blood supply.
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.
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.
Kashyap, Abhishek S.; Fernandez-Rodriguez, Laura; Zhao, Yun; Monaco, Gianni; Trefny, Marcel P.; Yoshida, Naohiro; Martin, Kea; Sharma, Ashwani; Olieric, Natacha; Shah, Pankaj; Stanczak, Michal; Kirchhammer, Nicole; Park, Sung-Moo; Wieckowski, Sebastien; Laubli, Heinz; Zagani, Rachid; Kasenda, Benjamin; Steinmetz, Michel O.; Reinecker, Hans-Christian; Zippelius, Alfred (September 2019). "GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses". Cell Reports. 28 (13): 3367–3380.e8. doi:10.1016/j.celrep.2019.08.057. PMC 6876861. PMID 31553907. Natoli, Marina; Herzig, Petra; Pishali Bejestani, Elham; Buchi, Melanie; Ritschard, Reto; Lloyd, G. Kenneth; Mohanlal, Ramon; Tonra, James R.; Huang, Lan; Heinzelmann, Viola; Trüb, Marta; Zippelius, Alfred; Kashyap, Abhishek S. (3 March 2021). "Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity". Frontiers in Oncology. 11. doi:10.3389/fonc.2021.644608. PMC 7966525. PMID 33747968. La Sala, Giuseppina; Olieric, Natacha; Sharma, Ashwani; Viti, Federica; de Asis Balaguer Perez, Francisco; Huang, Lan; Tonra, James R.; Lloyd, G. Kenneth; Decherchi, Sergio; Díaz, José Fernando; Steinmetz, Michel O.; Cavalli, Andrea (November 2019). "Structure, Thermodynamics, and Kinetics of Plinabulin Binding to Two Tubulin Isotypes". Chem. 5 (11): 2969–2986. doi:10.1016/j.chempr.2019.08.022. hdl:10261/198993.
