Plinabulin

{{Chembox

| ImageFile = Plinabulin.svg

| ImageSize = 200px

| IUPACName = (3Z,6Z)-3-Benzylidene-6-{[5-(2-methyl-2-propanyl)-1H-imidazol-4-yl]methylene}-2,5-piperazinedione

| OtherNames =

|Section1={{Chembox Identifiers

| CASNo = 714272-27-2

| CASNo_Ref = {{cascite|correct|}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 986FY7F8XR

| PubChem = 9949641

| ChemSpiderID = 8125252

| ChEBI = 177413

| KEGG = D09655

| SMILES = O=C3/C(=C/c1nc[nH]c1C(C)(C)C)NC(=O)C(=C\c2ccccc2)\N3

| 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-

| InChIKey = UNRCMCRRFYFGFX-TYPNBTCFBU

| StdInChI = 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-

| StdInChIKey = UNRCMCRRFYFGFX-TYPNBTCFSA-N

}}

|Section2={{Chembox Properties

| C=19 | H=20 | N=4 | O=2

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|Section3={{Chembox Hazards

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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.{{Cite web |date=2021-05-23 |title=Completed: Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced NSCLC (DUBLIN-3), Phase Three |url=https://clinicaltrials.gov/study/NCT02504489 |access-date=2024-07-19 |website=clinicaltrials.gov}} Plinabulin is being investigated for the reduction of chemotherapy-induced neutropenia{{cite conference

| title = Randomized Phase 2 Trial of Plinabulin (NPI-2358) Plus Docetaxel in Patients with Advanced Non-Small Lung Cancer (NSCLC)

| last1 = Heist | first1 = R.S.

| last2 = Aren | first2 = O.R.

| last3 = Mita | first3 = A.C.

| last4 = Polikoff | first4 = J.

| last5 = Bazhenova | first5 = L.

| last6 = Lloyd | first6 = G.K.

| last7 = Mikrut | first7 = W.

| last8 = Reich | first8 =W.

| last9 = Spear | first9 = M.A.

| last10 = Huang | first10 = L.

| year = 2014

| conference = J Clin Oncol 32:5s

| editor =

| volume =

| edition =

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}} and for anti-cancer effects in combination with immune checkpoint inhibitors{{cite web

| url = https://clinicaltrials.gov/show/NCT02846792

| title = Nivolumab and Plinabulin in Treating Patients With Stage IIIB-IV, Recurrent, or Metastatic Non-small Cell Lung Cancer

}}{{cite conference

| url = https://clinicaltrials.gov/show/NCT02812667

| title = Nivolumab in Combination With Plinabulin in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC)

}} and in KRAS mutated tumors.{{cite conference

| title = Activity of Plinabulin in Tumor Models with Kras Mutations

| last1 = Lloyd | first1 = G.K.

| last2 = Du | first2 = L.

| last3 = Lee | first3 = G.

| last4 = Dalsing-Hernandez | first4 = J.

| last5 = Kotlarczyk | first5 = K.

| last6 = Gonzalez | first6 = K.

| last7 = Nawrocki | first7 = S.

| last8 = Carew | first8 = J.

| last9 = Huang | first9= L.

| date = October 5–9, 2015

| conference = Proceedings of the International Conference on Molecular Targets and Cancer Therapeutics

| location = Boston MA

}}

Plinabulin blocks the polymerization of tubulin in a unique manner, resulting in multi-factorial effects including an enhanced immune-oncology response,{{cite journal |last1=Kashyap |first1=Abhishek S. |last2=Fernandez-Rodriguez |first2=Laura |last3=Zhao |first3=Yun |last4=Monaco |first4=Gianni |last5=Trefny |first5=Marcel P. |last6=Yoshida |first6=Naohiro |last7=Martin |first7=Kea |last8=Sharma |first8=Ashwani |last9=Olieric |first9=Natacha |last10=Shah |first10=Pankaj |last11=Stanczak |first11=Michal |last12=Kirchhammer |first12=Nicole |last13=Park |first13=Sung-Moo |last14=Wieckowski |first14=Sebastien |last15=Laubli |first15=Heinz |date=September 2019 |title=GEF-H1 Signaling upon Microtubule Destabilization Is Required for Dendritic Cell Activation and Specific Anti-tumor Responses |journal=Cell Reports |volume=28 |issue=13 |pages=3367–3380.e8 |last16=Zagani |first16=Rachid |last17=Kasenda |first17=Benjamin |last18=Steinmetz |first18=Michel O. |last19=Reinecker |first19=Hans-Christian |last20=Zippelius |first20=Alfred|doi=10.1016/j.celrep.2019.08.057 |pmid=31553907 |pmc=6876861 }}{{cite journal |last1=Natoli |first1=Marina |last2=Herzig |first2=Petra |last3=Pishali Bejestani |first3=Elham |last4=Buchi |first4=Melanie |last5=Ritschard |first5=Reto |last6=Lloyd |first6=G. Kenneth |last7=Mohanlal |first7=Ramon |last8=Tonra |first8=James R. |last9=Huang |first9=Lan |last10=Heinzelmann |first10=Viola |last11=Trüb |first11=Marta |last12=Zippelius |first12=Alfred |last13=Kashyap |first13=Abhishek S. |date=3 March 2021 |title=Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity |journal=Frontiers in Oncology |volume=11|doi=10.3389/fonc.2021.644608 |doi-access=free |pmid=33747968 |pmc=7966525 }}{{cite journal |last1=La Sala |first1=Giuseppina |last2=Olieric |first2=Natacha |last3=Sharma |first3=Ashwani |last4=Viti |first4=Federica |last5=de Asis Balaguer Perez |first5=Francisco |last6=Huang |first6=Lan |last7=Tonra |first7=James R. |last8=Lloyd |first8=G. Kenneth |last9=Decherchi |first9=Sergio |last10=Díaz |first10=José Fernando |last11=Steinmetz |first11=Michel O. |last12=Cavalli |first12=Andrea |date=November 2019 |title=Structure, Thermodynamics, and Kinetics of Plinabulin Binding to Two Tubulin Isotypes |journal=Chem |volume=5 |issue=11 |pages=2969–2986|doi=10.1016/j.chempr.2019.08.022 |hdl=10261/198993 |hdl-access=free }} activation of the JNK pathway{{cite journal

| last1 = Singh | first1 = A.V.

| last2 = Bandi | first2 = M.

| last3 = Raje | first3 = N.

| last4 = Richardson | first4 = P.

| last5 = Palladino | first5 = M.A.

| last6 = Chauhan | first6 = D.

| last7 = Anderson | first7 = K.

| title = A Novel Vascular Disrupting Agent Plinabulin Triggers JNK-Mediated Apoptosis and Inhibits Angiogenesis in Multiple Myeloma Cells

| journal = Blood

| year = 2011

| volume = 117

| issue = 21