Plinabulin (NPI-2358) acts as a vascular disrupting agent and inhibits tubulin depolymerization with an IC50 of 9.8 nM in HT-29 cells[1]. Plinabulin attaches to the colchicine binding site on β-tubulin, inhibiting its polymerization and exhibiting strong anti-tumor properties[2].
体内研究
Plinabulin, administered intraperitoneally at doses ranging from 0 mg/kg to 15 mg/kg to female CDF1 and C3H/He mice, results in a time- and dose-dependent reduction in tumor perfusion. KHT sarcoma exhibits a higher sensitivity to Plinabulin's anti-tumor effects compared to C3H tumors, with both models showing an enhanced response to radiation[3].
体外研究
Plinabulin (NPI-2358), in concentrations ranging from 2-200 nM and applied for 30 minutes to HUVECs cells, acts as a potent anti-tumor agent. It effectively induces tubulin depolymerization and increases monolayer permeability, showing activity against multidrug-resistant tumor cell lines with IC50 values of 18 nM for DU 145 cells, 13 nM for PC-3 cells, 14 nM for MDA-MB-231 cells, 18 nM for NCI-H292 cells, and 11 nM for Jurkat leukemia cells[1].
Plinabulin/普那布林 细胞实验
Cell Line
Concentration
Treated Time
Description
References
XS106 cells
200 nM
20 hours
To evaluate the effect of Plinabulin on the maturation of XS106 cells, results showed that Plinabulin significantly induced the expression of CD80 and CD86
Cell Rep. 2019 Sep 24;28(13):3367-3380.e8.
Splenic DCs
100 nM
20 hours
To evaluate the effect of Plinabulin on the maturation of splenic DCs, results showed that Plinabulin significantly induced the expression of CD80 and CD86
Cell Rep. 2019 Sep 24;28(13):3367-3380.e8.
SP37A3 cells
100 nM
20 hours
To evaluate the effect of Plinabulin on the maturation of SP37A3 cells, results showed that Plinabulin significantly induced the expression of CD80 and CD86
Cell Rep. 2019 Sep 24;28(13):3367-3380.e8.
HT-29 human colon cancer cells
2 nM (Z-1), 20 nM (Z-2), 200 nM (Z-3)
6 hours
Assessed microtubule network disruption via immunofluorescence imaging, showing Z-isomers induced abnormal tubulin aggregation at respective concentrations.
Nat Commun. 2022;13(1):6066.
Healthy human monocyte-derived macrophages
200 nM and 1000 nM
48 or 72 hours
To evaluate the effect of Plinabulin on human macrophage polarization. Results showed that Plinabulin treatment resulted in a dose-dependent increase in expression of CD80, a decrease of the M2 marker expression and a significant increase in the M1/M2 ratio.
Front Oncol. 2021 Mar 3;11:644608.
Murine bone marrow-derived macrophages (BMDM)
200 nM and 1000 nM
48 or 72 hours
To evaluate the effect of Plinabulin on macrophage polarization. Results showed that Plinabulin treatment led to a significant, dose-dependent increase in M1 markers CD80 and CD86 and a concomitant decrease in expression of CD206.
Front Oncol. 2021 Mar 3;11:644608.
HepaRG Cells Cryopreserved
30 μM
2 hours
Evaluation of Plinabulin metabolites in HepaRG cells, identifying 2 phase-II sulfate conjugate metabolites.
ACS Omega. 2022 Jun 14;7(25):21465-21472.
Human liver microsomes (HLMs)
30 μM
90 minutes
Evaluation of Plinabulin metabolites in the presence of NADPH, identifying 17 phase-I metabolites including isomerization, hydroxylation, hydration, and oxygenation products.
ACS Omega. 2022 Jun 14;7(25):21465-21472.
Plinabulin/普那布林 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6N wild-type mice and C57BL/6N Rag2−/− mice
Subcutaneous MC38 colon cancer model
Peritumoral injection
7.0 mg/kg
Seven doses over 11 days
To evaluate the effect of Plinabulin on tumor growth and macrophage polarization in the tumor microenvironment. Results showed that Plinabulin treatment significantly inhibited tumor growth and increased the proportion of M1-like TAMs in the tumor.
Front Oncol. 2021 Mar 3;11:644608.
Wistar rats
Leukopenia model
Intravenous injection
0.5 mg/kg, 1 mg/kg, 3 mg/kg
Single dose, observed for 10 hours
To investigate the pharmacokinetic differences of Plinabulin between leukopenic and normal rats. Results showed no significant pharmacokinetic differences between the leukopenic and normal groups.
Pharmaceuticals (Basel). 2023 Aug 14;16(8):1153
Zebrafish larvae
Zebrafish PTZ seizure model
Water immersion
1.25–10 µM
2 hours or 18 hours
Evaluate the antiseizure activity of Plinabulin, showing significant reduction in PTZ-induced seizure behavior after 18 hours of treatment
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