Plinabulin

Last updated
Plinabulin
Plinabulin.svg
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
PubChem CID
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).

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.

Related Research Articles

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<span class="mw-page-title-main">Non-small-cell lung cancer</span> Any type of epithelial lung cancer other than small-cell lung carcinoma

Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitive to chemotherapy, compared to small-cell carcinoma. When possible, they are primarily treated by surgical resection with curative intent, although chemotherapy has been used increasingly both preoperatively and postoperatively.

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Nivolumab, sold under the brand name Opdivo, is an anti-cancer medication used to treat a number of types of cancer. This includes melanoma, lung cancer, malignant pleural mesothelioma, renal cell carcinoma, Hodgkin lymphoma, head and neck cancer, urothelial carcinoma, colon cancer, esophageal squamous cell carcinoma, liver cancer, gastric cancer, and esophageal or gastroesophageal junction cancer. It is administered intravenously.

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References

  1. "Completed: Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC (DUBLIN-3), Phase Three". clinicaltrials.gov. 2021-05-23. Retrieved 2024-07-19.
  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. 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.
  7. 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.
  8. 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.
  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. PMC   3110026 . PMID   21454451.