Name: ARRY 520 trifluoroacetate
Brand: GlpBio
SKU: GC11656
Availability: InStock
Rating: 5 (30 reviews)

GlpBio Products Cited In Reputable Papers

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610.7931 (2022): 366-372

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Product Documents

Quality Control & SDS

View current batch:

Purity: >99.50%

Protocol

Cell experiment:

Exponentially growing cells (0.4×106/mL) are treated with Filanesib (ARRY-520) for up to 48 hours. For combination, HL-60 and HL-60Bcl-2 cells (0.4×106/mL) are incubated with Filanesib (ARRY-520), ABT-737, or both for up to 96 hours. DMSO is used as the control agent. Apoptosis is estimated by flow cytometry measurements of phosphatidyl serine with the Annexin-V-FLUOS Staining Kit. Membrane integrity is simultaneously assessed by 7-amino-actinomycin D (7-AAD). To measure changes in the mitochondrial membrane potential (MMP), cells are loaded with CMXRos (300 nM) and MitoTracker Green (500 nM) for 1 hour at 37°C. The loss of MMP is then assessed by measuring CMXRos retention while simultaneously adjusting for mitochondrial mass.

Animal experiment:

Subcutaneous tumor xenografts are allowed to grow to a volume of 250-350 mm3. The mice are randomized into groups of 3-4 based on tumor size, and are given a single dose of Filanesib (ARRY-520) i.p. At various time-points after administration of the drug, the mice are euthanized by CO2 inhalation and the tumors excised and placed in 10% neutral buffered formalin. The formalin-fixed tumors are processed and paraffin embedded by standard procedures. Spindle morphology is analyzed by staining tumor sections for α-tubulin, and apoptosis is analyzed by TUNEL stain. Monopolar/abnormal spindles and TUNEL positive (apoptotic) cells are counted in three ×40 fields from each sample, analyzed using algorithms developed in ImagePro software.

References:

[1]. Woessner R, et al. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res. 2009 Nov;29(11):4373-80.
[2]. Tunquist BJ, et al. Mcl-1 stability determines mitotic cell fate of human multiple myeloma tumor cells treated with the kinesin spindle protein inhibitor ARRY-520. Mol Cancer Ther. 2010 Jul;9(7):2046-56.
[3]. Kim KH, et al. KSP inhibitor ARRY-520 as a substitute for Paclitaxel in Type I ovarian cancer cells. J Transl Med. 2009 Jul 20;7:63.
[4]. Carter BZ, et al. Inhibition of KSP by ARRY-520 induces cell cycle block and cell death via the mitochondrial pathway in AML cells. Leukemia. 2009 Oct;23(10):1755-62.

ARRY 520 trifluoroacetate is a synthetic and salt form of KSP inhibitor with IC50 value of 6 nM.

Kinesin spindle protein (KSP) is one member of the mitotic kinesins involved in the early stages of mitosis responsible for centrosome separation.

In vitro: ARRY-520 had low nanomolar antiproliferative activity in various tumor cell lines and exhibited activity in multidrug-resistant cell lines. EC50s of ARRY-520 for proliferation inhibition in HCT-15, NCI/ADR-RES and K562/ADR cells was 3.7, 14 and 4.2 nM, respectively, while paclitaxel EC50s in these cell lines was 35, 565 and 372 nM. Moreover, K562/ADR was found to be 118-fold resistant to paclitaxel when compared to the parent K562 line, but only 3.5-fold resistant to that of ARRY-520 [1].

In vivo: ARRY-520 was found to be active in UISO-BCA-1 xenografts, which were completely resistant to paclitaxel. The antitumor efficacy of ARRY-520 was also found to be superior to paclitaxel in mice bearing HT-29, HCT-116, MDA-MB-231 and A2780 xenografts. ARRY-520 was superior to docetaxel in the androgen receptor-negative prostate cancer PC-3 xenograft model, and was also superior to docetaxel in the DU145 prostate xenograft model [1].

Clinical trial: A phase I trial was conducted to establish the safety and the maximum tolerated dose (MTD) of ARRY-520. The MTD was 4.5 mg/m2 total dose per cycle for both dose schedules. Dose-limiting toxicities included exfoliative rash, hand-foot-syndrome, mucositis, and hyperbilirubinemia. Grades 3 or 4 reversible drug-related myelosuppression were observed in 33 of 36 patients [2].

References:
[1] Woessner R, Tunquist B, Lemieux C, Chlipala E, Jackinsky S, Dewolf W Jr, Voegtli W, Cox A, Rana S, Lee P, Walker D. ARRY-520, a novel KSP inhibitor with potent activity in hematological and taxane-resistant tumor models. Anticancer Res. 2009;29(11):4373-80.
[2] Khoury HJ, Garcia-Manero G, Borthakur G, Kadia T, Foudray MC, Arellano M, Langston A, Bethelmie-Bryan B, Rush S, Litwiler K, Karan S, Simmons H, Marcus AI, Ptaszynski M, Kantarjian H. A phase 1 dose-escalation study of ARRY-520, a kinesin spindle protein inhibitor, in patients with advanced myeloid leukemias. Cancer. 2012;118(14):3556-64.

Cas No.	885060-09-3	SDF
Synonyms	Filanesib
Chemical Name	(2S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3-carboxamide
Canonical SMILES	CN(C(=O)N1C(SC(=N1)C2=C(C=CC(=C2)F)F)(CCCN)C3=CC=CC=C3)OC
Formula	C₂₀H₂₂F₂N₄O₂S.CF₃CO₂H	M.Wt	420.48
Solubility	DMF: 20 mg/ml,DMSO: 20 mg/ml,Ethanol: 20 mg/ml,PBS (pH 7.2): 0.2 mg/ml	Storage	Store at -20°C
General tips	Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition	Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
		1 mg	5 mg	10 mg
	1 mM	2.3782 mL	11.8912 mL	23.7823 mL
	5 mM	0.4756 mL	2.3782 mL	4.7565 mL
	10 mM	0.2378 mL	1.1891 mL	2.3782 mL

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

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ARRY 520 trifluoroacetate (Synonyms: Filanesib)

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