Chemistry:Plinabulin

From HandWiki

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]

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.

References

  1. ↑ "Completed: Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC (DUBLIN-3), Phase Three". 2021-05-23. https://clinicaltrials.gov/study/NCT02504489. 
  2. ↑ Heist, R.S.; Aren, O.R.; Mita, A.C.; Polikoff, J.; Bazhenova, L.; Lloyd, G.K.; Mikrut, W.; Reich, W. et al. (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". https://clinicaltrials.gov/show/NCT02846792. 
  4. ↑ "Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)". https://clinicaltrials.gov/show/NCT02812667. 
  5. ↑ Lloyd, G.K.; Du, L.; Lee, G.; Dalsing-Hernandez, J.; Kotlarczyk, K.; Gonzalez, K.; Nawrocki, S.; Carew, J. et al. (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. ↑ Kashyap, Abhishek S.; Fernandez-Rodriguez, Laura; Zhao, Yun; Monaco, Gianni; Trefny, Marcel P.; Yoshida, Naohiro; Martin, Kea; Sharma, Ashwani et al. (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. PMID 31553907. 
  7. ↑ Natoli, Marina; Herzig, Petra; Pishali Bejestani, Elham; Buchi, Melanie; Ritschard, Reto; Lloyd, G. Kenneth; Mohanlal, Ramon; Tonra, James R. et al. (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. PMID 33747968. 
  8. ↑ La Sala, Giuseppina; Olieric, Natacha; Sharma, Ashwani; Viti, Federica; de Asis Balaguer Perez, Francisco; Huang, Lan; Tonra, James R.; Lloyd, G. Kenneth et al. (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. 
  9. ↑ 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. PMID 21454451. 



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