Plinabulin
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MedKoo CAT#: 202040

CAS#: 714272-27-2 (plinabulin)

Description: 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

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Plinabulin
CAS# 714272-27-2 (plinabulin)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 202040
Name: Plinabulin
CAS#: 714272-27-2 (plinabulin)
Chemical Formula: C19H20N4O2
Exact Mass: 336.16
Molecular Weight: 336.390
Elemental Analysis: C, 67.84; H, 5.99; N, 16.66; O, 9.51

Price and Availability

Size Price Availability Quantity
10mg USD 90 Ready to ship
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1350 Ready to ship
1g USD 1950 Ready to ship
2g USD 2950 Ready to ship
5g USD 4950 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/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 20.0 59.50

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.

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1: Yakushiji F, Tanaka H, Muguruma K, Iwahashi T, Yamazaki Y, Hayashi Y. Prodrug study of plinabulin using a click strategy focused on the effects of a replaceable water-solubilizing moiety. Chem Pharm Bull (Tokyo). 2012;60(7):877-81. PubMed PMID: 22790821.

2: Yakushiji F, Tanaka H, Muguruma K, Iwahashi T, Yamazaki Y, Hayashi Y. Water-soluble prodrug of antimicrotubule agent plinabulin: effective strategy with click chemistry. Chemistry. 2011 Nov 4;17(45):12587-90. doi: 10.1002/chem.201102293. Epub 2011 Sep 29. PubMed PMID: 21956869.

3: Bertelsen LB, Shen YY, Nielsen T, Stødkilde-Jørgensen H, Lloyd GK, Siemann DW, Horsman MR. Vascular effects of plinabulin (NPI-2358) and the influence on tumour response when given alone or combined with radiation. Int J Radiat Biol. 2011 Nov;87(11):1126-34. doi: 10.3109/09553002.2011.605418. PubMed PMID: 21815749; PubMed Central PMCID: PMC3509771.

4: 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. PubMed PMID: 21454451; PubMed Central PMCID: PMC3110026.

5: Millward M, Mainwaring P, Mita A, Federico K, Lloyd GK, Reddinger N, Nawrocki S, Mita M, Spear MA. Phase 1 study of the novel vascular disrupting agent plinabulin (NPI-2358) and docetaxel. Invest New Drugs. 2012 Jun;30(3):1065-73. doi: 10.1007/s10637-011-9642-4. Epub 2011 Feb 16. PubMed PMID: 21327495.

6: Mita MM, Spear MA, Yee LK, Mita AC, Heath EI, Papadopoulos KP, Federico KC, Reich SD, Romero O, Malburg L, Pilat M, Lloyd GK, Neuteboom ST, Cropp G, Ashton E, LoRusso PM. Phase 1 first-in-human trial of the vascular disrupting agent plinabulin(NPI-2358) in patients with solid tumors or lymphomas. Clin Cancer Res. 2010 Dec 1;16(23):5892-9. doi: 10.1158/1078-0432.CCR-10-1096. PubMed PMID: 21138873.

7: Yamazaki Y, Kido Y, Hidaka K, Yasui H, Kiso Y, Yakushiji F, Hayashi Y. Tubulin photoaffinity labeling study with a plinabulin chemical probe possessing a biotin tag at the oxazole. Bioorg Med Chem. 2011 Jan 1;19(1):595-602. doi: 10.1016/j.bmc.2010.10.055. Epub 2010 Oct 31. PubMed PMID: 21106379.

8: Yamazaki Y, Sumikura M, Hidaka K, Yasui H, Kiso Y, Yakushiji F, Hayashi Y. Anti-microtubule 'plinabulin' chemical probe KPU-244-B3 labeled both alpha- and beta-tubulin. Bioorg Med Chem. 2010 May 1;18(9):3169-74. doi: 10.1016/j.bmc.2010.03.037. Epub 2010 Mar 23. PubMed PMID: 20395148.