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MedKoo Cat#: 202040 | Name: Plinabulin
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Plinabulin is a VDA of novel structure in having been derived from a marine microbial source, as opposed to terrestrial sources for other VDAs. Plinabulin binds to the colchicine binding site of b-tubulin preventing polymerization and disrupting the cytoplasmic microtubule network. Plinabulin has been shown to produce anti-tumor activity in animal models as a single agent and synergistically with other chemotherapy agents including taxanes. Overall, preclinical studies indicated plinabulin had a favorable safety and activity profile leading to the initiation of clinical trials. Favorable data from early clinical studies lead to the initiation of a Phase 2 clinical trial program.

Chemical Structure

Plinabulin
Plinabulin
CAS#714272-27-2 (plinabulin)

Theoretical Analysis

MedKoo Cat#: 202040

Name: Plinabulin

CAS#: 714272-27-2 (plinabulin)

Chemical Formula: C19H20N4O2

Exact Mass: 336.1586

Molecular Weight: 336.39

Elemental Analysis: C, 67.84; H, 5.99; N, 16.66; O, 9.51

Price and Availability

Size Price Availability Quantity
10mg USD 90.00 Ready to ship
25mg USD 150.00 Ready to ship
50mg USD 250.00 Ready to ship
100mg USD 450.00 Ready to ship
200mg USD 750.00 Ready to ship
500mg USD 1,350.00 Ready to ship
1g USD 1,950.00 Ready to ship
2g USD 2,950.00 Ready to ship
5g USD 4,950.00 Ready to ship
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Related CAS #
714272-27-2 (plinabulin) 2054938-28-0 (deuterated form)
Synonym
NPI 2358; NPI2358; NPI-2358; Plinabulin
IUPAC/Chemical Name
(3E,6E)-3-benzylidene-6-((5-(tert-butyl)-1H-imidazol-4-yl)methylene)piperazine-2,5-dione
InChi Key
UNRCMCRRFYFGFX-AOEKMSOUSA-N
InChi Code
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+
SMILES Code
O=C(/C(NC/1=O)=C\C2=CC=CC=C2)NC1=C\C3=C(C(C)(C)C)NC=N3
Appearance
Yellow solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
           
Biological target:
Plinabulin (NPI-2358) is a vascular disrupting agent (VDA) against β-tubulin -depolymerizing with an IC50 of 9.8 nM against HT-29 cells.
In vitro activity:
To examine the antivascular activity of plinabulin, capillary tubule formation assays were performed with the use of HUVECs. Even low concentrations of plinabulin (5nM treatment for 12 hours) triggered significantly decreased tubule formation in HUVECs (Figure 3A; 70%-80% decrease; P < .05; n = 3). To further confirm the antivascular activity of plinabulin, the effects of plinabulin on the chemotactic motility of both MM and endothelial cells were examined with the use of trans-well insert assays. A marked reduction was observed in serum-dependent migration in plinabulin-treated MM cells (Figure 3B; 58% ± 2.1% inhibition in plinabulin-treated vs control; P < .05). At this concentration 5nM plinabulin for 12 hours did not affect survival of MM cells (> 95% viable cells). Similar effects of plinabulin were noted against HUVECs (Figure 3C; 48% ± 1.7% decrease in migration; P < .05). Together, these data suggest that plinabulin disrupts tumor vasculature by inhibiting both cell migration and endothelial cell tubule formation. Blood. 2011 May 26; 117(21): 5692–5700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110026/
In vivo activity:
MM.1S tumor-bearing mice were treated with plinabulin (7.5 mg/kg intraperitoneally) or vehicle alone twice a week for 3 weeks. Plinabulin treatment inhibited tumor growth and prolonged survival in mice (Figure 7A,C; P < .05). Plinabulin treatment was well tolerated, without significant weight loss (Figure 7B). Importantly, increased survival was noted in mice receiving plinabulin versus vehicle alone (P = .0041); median survival in the control group was 15 days versus 35 days in the plinabulin treatment group (Figure 7C). Tumors from plinabulin-treated compared with control mice were next examined, and immunostaining for cleaved caspase-3 and vasculature-related marker such as factor VIII was performed. As shown in Figure 7D, increase in cleaved caspase-3 was observed in tumor sections from the plinabulin-treated group versus the control group (Figure 7D bottom). Moreover, antivascular activity of plinabulin was evidenced by a significant reduction in factor VIII expression (Figure 7D top). These results show that in vivo antiMM activity of plinabulin is associated with disruption of tumor vasculature and proapoptotic activity. Blood. 2011 May 26; 117(21): 5692–5700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110026/
Solvent mg/mL mM
Solubility
DMSO 20.0 59.50
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 336.39 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Cimino PJ, Huang L, Du L, Wu Y, Bishop J, Dalsing-Hernandez J, Kotlarczyk K, Gonzales P, Carew J, Nawrocki S, Jordan MA, Wilson L, Lloyd GK, Wirsching HG. Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling. Biomed Rep. 2019 Apr;10(4):218-224. doi: 10.3892/br.2019.1196. Epub 2019 Mar 5. PMID: 30972217; PMCID: PMC6439430. 2. Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, Anderson KC. A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood. 2011 May 26;117(21):5692-700. doi: 10.1182/blood-2010-12-323857. Epub 2011 Mar 31. PMID: 21454451; PMCID: PMC3110026.
In vitro protocol:
1. Cimino PJ, Huang L, Du L, Wu Y, Bishop J, Dalsing-Hernandez J, Kotlarczyk K, Gonzales P, Carew J, Nawrocki S, Jordan MA, Wilson L, Lloyd GK, Wirsching HG. Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling. Biomed Rep. 2019 Apr;10(4):218-224. doi: 10.3892/br.2019.1196. Epub 2019 Mar 5. PMID: 30972217; PMCID: PMC6439430. 2. Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, Anderson KC. A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood. 2011 May 26;117(21):5692-700. doi: 10.1182/blood-2010-12-323857. Epub 2011 Mar 31. PMID: 21454451; PMCID: PMC3110026.
In vivo protocol:
1. Cimino PJ, Huang L, Du L, Wu Y, Bishop J, Dalsing-Hernandez J, Kotlarczyk K, Gonzales P, Carew J, Nawrocki S, Jordan MA, Wilson L, Lloyd GK, Wirsching HG. Plinabulin, an inhibitor of tubulin polymerization, targets KRAS signaling through disruption of endosomal recycling. Biomed Rep. 2019 Apr;10(4):218-224. doi: 10.3892/br.2019.1196. Epub 2019 Mar 5. PMID: 30972217; PMCID: PMC6439430. 2. Singh AV, Bandi M, Raje N, Richardson P, Palladino MA, Chauhan D, Anderson KC. A novel vascular disrupting agent plinabulin triggers JNK-mediated apoptosis and inhibits angiogenesis in multiple myeloma cells. Blood. 2011 May 26;117(21):5692-700. doi: 10.1182/blood-2010-12-323857. Epub 2011 Mar 31. PMID: 21454451; PMCID: PMC3110026.
1: Lv J, Xu Y, Liu Y, Sakurai K, Yu H, Tang Z. Co-delivery of Plinabulin and Tirapazamine boosts anti-tumor efficacy by simultaneously destroying tumor blood vessels and killing tumor cells. Biomaterials. 2024 Sep;309:122586. doi: 10.1016/j.biomaterials.2024.122586. Epub 2024 Apr 30. PMID: 38718615. 2: Wang S, Zhong C, Li F, Ding Z, Tang Y, Li W. Design, synthesis, and structure-activity relationship study of novel plinabulin derivatives as anti- tumor agents based on the co-crystal structure. Mol Divers. 2024 Apr 23. doi: 10.1007/s11030-024-10835-7. Epub ahead of print. PMID: 38652366. 3: Seliwjorstow A, Takamiya M, Rastegar S, Pianowski Z. Reversible Influence of Hemipiperazine Photochromism on the Early Development of Zebrafish Embryo. Chembiochem. 2024 Apr 16;25(8):e202400143. doi: 10.1002/cbic.202400143. Epub 2024 Mar 22. PMID: 38442077. 4: Niu X, Chen D, He W, Tang Y, Zhao J. Development and Validation of a Novel UHPLC-MS/MS Method for the Quantification of Plinabulin in Plasma and Its Application in a Pharmacokinetic Study with Leukopenic Rats. Pharmaceuticals (Basel). 2023 Aug 14;16(8):1153. doi: 10.3390/ph16081153. PMID: 37631067; PMCID: PMC10459361. 5: Fang S, Bi S, Li Y, Tian S, Xu H, Fu L, Wang S, Tang Y, Qiu P. Design, synthesis and anti-tumor evaluation of plinabulin derivatives as potential agents targeting β-tubulin. Bioorg Med Chem Lett. 2023 Jul 15;91:129370. doi: 10.1016/j.bmcl.2023.129370. Epub 2023 Jun 8. PMID: 37301522. 6: Crawford J, Oswalt C. The impact of new and emerging agents on outcomes for febrile neutropenia: addressing clinical gaps. Curr Opin Oncol. 2023 Jul 1;35(4):241-247. doi: 10.1097/CCO.0000000000000952. Epub 2023 May 3. PMID: 37222193. 7: Liu J, Chen M, Gao X, Liu X, Zhao J, Pan R, Zhong W, Xu Y, Wang M. Study protocol of KeyPemls-004: A phase 2 study of pembrolizumab in combination with plinabulin and docetaxel in previously treated patients with metastatic non- small cell lung cancer and progressive disease (PD) after immunotherapy (PD-1/PD-L1 inhibitor) alone or in combination with platinum-doublet chemotherapy. Thorac Cancer. 2023 Mar;14(8):773-778. doi: 10.1111/1759-7714.14806. Epub 2023 Feb 1. PMID: 36725772; PMCID: PMC10008678. 8: Chu Y, Tian Z, Yang M, Li W. Conformation and energy investigation of microtubule longitudinal dynamic instability induced by natural products. Chem Biol Drug Des. 2023 Sep;102(3):444-456. doi: 10.1111/cbdd.14189. Epub 2022 Dec 15. PMID: 36509697. 9: Kirchner S, Leistner AL, Gödtel P, Seliwjorstow A, Weber S, Karcher J, Nieger M, Pianowski Z. Hemipiperazines as peptide-derived molecular photoswitches with low-nanomolar cytotoxicity. Nat Commun. 2022 Oct 14;13(1):6066. doi: 10.1038/s41467-022-33750-7. PMID: 36241620; PMCID: PMC9568564. 10: Suo L, Dai W, Qin X, Li G, Zhang D, Cheng T, Yao T, Zhang C. Screening of primary open-angle glaucoma diagnostic markers based on immune-related genes and immune infiltration. BMC Genom Data. 2022 Aug 24;23(1):67. doi: 10.1186/s12863-022-01072-8. PMID: 36002796; PMCID: PMC9400315. 11: Xu Y, Lv J, Shen N, Tang Z, Chen X. A self-activating nanoized vascular disrupting agent for selective anti-tumor therapy. Biomaterials. 2022 Sep;288:121736. doi: 10.1016/j.biomaterials.2022.121736. Epub 2022 Aug 14. PMID: 35995623. 12: Al-Shakliah NS, Kadi AA, Al-Salahi R, Rahman AFMM. In Vitro Identification of Potential Metabolites of Plinabulin (NPI 2358) in Hepatic Preparations Using Liquid Chromatography-Ion Trap Mass Spectrometry. ACS Omega. 2022 Jun 14;7(25):21465-21472. doi: 10.1021/acsomega.2c00929. PMID: 35785266; PMCID: PMC9245099. 13: Copmans D, Kildgaard S, Roux E, Partoens M, Steurs G, Wang X, De Borggraeve WM, Esguerra CV, Crawford AD, Larsen TO, de Witte PAM. From the North Sea to Drug Repurposing, the Antiseizure Activity of Halimide and Plinabulin. Pharmaceuticals (Basel). 2022 Feb 18;15(2):247. doi: 10.3390/ph15020247. PMID: 35215359; PMCID: PMC8878679. 14: Blayney DW, Mohanlal R, Adamchuk H, Kirtbaya DV, Chen M, Du L, Ogenstad S, Ginn G, Huang L, Zhang Q. Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Docetaxel-Induced Neutropenia in Patients With Solid Tumors: A Randomized Clinical Trial. JAMA Netw Open. 2022 Jan 4;5(1):e2145446. doi: 10.1001/jamanetworkopen.2021.45446. PMID: 35084480; PMCID: PMC8796017. 15: Natoli M, Herzig P, Pishali Bejestani E, Buchi M, Ritschard R, Lloyd GK, Mohanlal R, Tonra JR, Huang L, Heinzelmann V, Trüb M, Zippelius A, Kashyap AS. Plinabulin, a Distinct Microtubule-Targeting Chemotherapy, Promotes M1-Like Macrophage Polarization and Anti-tumor Immunity. Front Oncol. 2021 Mar 3;11:644608. doi: 10.3389/fonc.2021.644608. PMID: 33747968; PMCID: PMC7966525. 16: Blayney DW, Zhang Q, Feng J, Zhao Y, Bondarenko I, Vynnychenko I, Kovalenko N, Nair S, Ibrahim E, Udovista DP, Mohanlal R, Ogenstad S, Ette E, Du L, Huang L, Shi YK. Efficacy of Plinabulin vs Pegfilgrastim for Prevention of Chemotherapy-Induced Neutropenia in Adults With Non-Small Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA Oncol. 2020 Nov 1;6(11):e204429. doi: 10.1001/jamaoncol.2020.4429. Epub 2020 Nov 12. PMID: 32970104; PMCID: PMC7516815. 17: Ding Z, Li F, Zhong C, Li F, Liu Y, Wang S, Zhao J, Li W. Structure-based design and synthesis of novel furan-diketopiperazine-type derivatives as potent microtubule inhibitors for treating cancer. Bioorg Med Chem. 2020 May 15;28(10):115435. doi: 10.1016/j.bmc.2020.115435. Epub 2020 Mar 13. PMID: 32278711. 18: Tonra JR, Lloyd GK, Mohanlal R, Huang L. Plinabulin ameliorates neutropenia induced by multiple chemotherapies through a mechanism distinct from G-CSF therapies. Cancer Chemother Pharmacol. 2020 Feb;85(2):461-468. doi: 10.1007/s00280-019-03998-w. Epub 2019 Dec 6. PMID: 31811421; PMCID: PMC7015961. 19: Liu Y, Zang R, Li F, Shi C, Zhao J, Zhong L, Wang X, Yang J, Li W. Combination of a novel microtubule inhibitor MBRI-001 and gemcitabine synergistically induces cell apoptosis by increasing DNA damage in pancreatic cancer cell lines. Invest New Drugs. 2020 Oct;38(5):1207-1217. doi: 10.1007/s10637-019-00874-5. Epub 2019 Dec 4. PMID: 31802375. 20: Ding Z, Ma M, Zhong C, Wang S, Fu Z, Hou Y, Liu Y, Zhong L, Chu Y, Li F, Song C, Wang Y, Yang J, Li W. Development of novel phenoxy-diketopiperazine-type plinabulin derivatives as potent antimicrotubule agents based on the co-crystal structure. Bioorg Med Chem. 2020 Jan 1;28(1):115186. doi: 10.1016/j.bmc.2019.115186. Epub 2019 Nov 11. PMID: 31759826.