Bortezomib

Biological Activity

Bortezomib (Velcade) is a highly selective, reversible inhibitor of the 26S proteasome with a ki value of 6nM, which has shown high antimyeloma activity. Bortezomib caused comparable growth suppression in LNCaP-Pro5 and PC3M-Pro4 cells with an IC90 of 10 nM.

Product Citations

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  Sci Rep. 2020 Feb 25;10(1):3386.

  Gender-specific Changes in Energy Metabolism and Protein Degradation as Major Pathways Affected in Livers of Mice Treated With Ibuprofen
  Bortezomib purchased from AbMole

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  Cell Physiol Biochem. 2018;50(6):2341-2364.

  Peperomin E Induces Promoter Hypomethylation of Metastatic-Suppressor Genes and Attenuates Metastasis in Poorly Differentiated Gastric Cancer.
  Bortezomib purchased from AbMole

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  Int J Oncol. 2016 Oct;49(4):1469-78.

  Metabotropic glutamate receptor 3 is involved in B-cell-related tumor apoptosis
  Bortezomib purchased from AbMole

Customer Product Validations & Biological Datas

	Source	INTERNATIONAL JOURNAL OF ONCOLOGY (2016) . Figure 9. Bortezomib (M1686) was from Abmole Bioscience Inc. (Houston, TX, USA)
	Method	FACS
	Cell Lines	B cells from CD19 cre/+Foxo1F/+ and CD19 cre/+Foxo1F/F mice
	Concentrations	0.05 μg/ml
	Incubation Time	24 h
	Results	The effect of Foxo1-defciency on cell apoptosis was approved by using B cells from CD19cre/+Foxo1F/+ and CD19cre/+Foxo1F/F (Fig. 9D).

	Source	INTERNATIONAL JOURNAL OF ONCOLOGY (2016) . Figure 5. MBortezomib (M1686) was from Abmole Bioscience Inc. (Houston, TX, USA)
	Method	FACS
	Cell Lines	SP2/0 cells
	Concentrations	0, 0.05 and 0.25 μg/ml
	Incubation Time	24 h
	Results	Low dose of bortezomib, frst-line drug in patients with newly diagnosed multiple myeloma, could effectively induce apoptosis and Grm3 expression (Fig. 5).

Protocol

Cell Experiment
Cell lines	Nine canine melanoma cell lines (CMM-1, CMM-2, ChMC, KMeC, LMeC, OMJ, OMS, OMK, and NML)
Preparation method	Cell growth inhibition assay Nine canine melanoma cell lines (CMM-1, CMM-2, ChMC, KMeC, LMeC, OMJ, OMS, OMK, and NML) were cultured in 96-well plates (2 *102 cells/well) for 24 h in cDMEM and treated with different concentrations of bortezomib (0–100 nM) for 72 h. Cell viability was then measured by a WST-1 cell proliferation assay kit (Takara) and the half maximal inhibitory concentration (IC50) of bortezomib for each cell line was calculated using the GraphPad Prism software (GraphPad Software).
Concentrations	0–100 nM
Incubation time	72 h

Animal Experiment
Animal models	CMM-1 cells in xenograft mouse models
Formulation	100 µL PBS containing 4.2% DMSO
Dosages	0.8mg/kg twice weekly
Administration	intravenous(IV) injections

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

Chemical Information

References

Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes
Andrew Sandstrom, et al. Science. 2019 Apr 5;364(6435):eaau1330. PMID: 30872533.

N-terminal degradation activates the NLRP1B inflammasome
Ashley J Chui, et al. Science. 2019 Apr 5;364(6435):82-85. PMID: 30872531.

Early onset of paralytic ileus caused by simultaneous administration of bortezomib and azole antifungals in multiple myeloma patients.
Koda et al. Rinsho Ketsueki. 2012 Aug;53(8):760-4. PMID: 22975816.

BTK inhibitor ibrutinib is cytotoxic to myeloma and potently enhances bortezomib and lenalidomide activities through NF-κB.
Rushworth et al. Cell Signal. 2012 Sep 10. PMID: 22975686.

A small molecule inhibitor of ubiquitin-specific protease-7 induces apoptosis in multiple myeloma cells and overcomes bortezomib resistance.
Chauhan et al. Cancer Cell. 2012 Sep 11;22(3):345-58. PMID: 22975377.

Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell lymphoma.
Jung et al. Am J Hematol. 2012 Aug 2. PMID: 22965904.