| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Filanesib TFA (formerly ARRY520 trifluoroacetic acid) is a novel, potent and synthetic small molecule inhibitor of kinesin spindle protein (KSP) with anticancer activity. It inhibits KSP with IC50 of 6 nM. Kinesin spindle protein (KSP), a microtubule-associated motor protein essential for cell cycle progression, is overexpressed in many cancers and is a potential anti-tumor target. Filanesib blocked cell cycle progression, leading to apoptosis in acute myeloid leukemia cell lines that express high levels of KSP. Knockdown of p53, overexpression of XIAP and mutation in caspase-8 did not significantly affect sensitivity to ARRY-520, suggesting that the response is independent of p53, XIAP and the extrinsic apoptotic pathway. Although ARRY-520 induced mitotic arrest in both HL-60 and Bcl-2-overexpressing HL-60Bcl-2 cells, cell death was blunted in HL-60Bcl-2 cells, suggesting that the apoptotic program is executed through the mitochondrial pathway. Accordingly, inhibition of Bcl-2 by ABT-737 was synergistic with ARRY-520 in HL-60Bcl-2 cells. Furthermore, ARRY-520 increased Bim protein levels prior to caspase activation in HL-60 cells. ARRY-520 significantly inhibited tumor growth of xenografts in SCID mice and inhibited AML blast but not normal colony formation, supporting a critical role for KSP in proliferation of leukemic progenitor cells. These results demonstrate that ARRY-520 potently induces cell cycle block and subsequent death in leukemic cells via the mitochondrial pathway and has the potential to eradicate AML progenitor cells.
| ln Vitro |
Filanesib TFA inhibits human KSP with an IC50 of 6 nM via a mechanism that has been shown to be uncompetitive with ATP and noncompetitive with tubulin[1]. Filanesib TFA causes mitotic arrest in several cell lines[1]. Filanesib TFA inhibits the proliferation of a wide spectrum of human and rodent tumor cell lines[1]. Filanesib TFA (0.001-0.1 nM; 36 hours) promotes apoptosis by a mechanism that is independent of p53 status, as indicated by nucleosome formation, caspase 3 and 7 activation, and accumulation in SubG0/1 by FACS [1]. Filanesib TFA (0.1-100 nM; 18 hours) increases the buildup of phospho-Histone H3 (a mitosis marker and indicative of mitotic arrest) in HeLa cells [1]. Filanesib TFA (0.78-6.25 nM; 44 hours) administration induces G2/M arrest [1]. Filanesib TFA (10 nM; 16 hours) administration causes the development of monopolar spindles[1]. Filanesib TFA potently promotes cell cycle arrest and subsequent death in leukemic cells via the mitochondrial pathway, with the ability to eliminate AML progenitor cells[2]. Filanesib TFA (3 μM, 6-24 hours) activates caspase-2 [3]. Filanesib TFA (0.003-3 μM; 24-48 hours) exhibits cytotoxicity in Type II EOC cells [3].
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| ln Vivo |
Anti-tumor efficacy of filanesib TFA (20 mg/kg, 30 mg/kg; ip; q4dx3) has been seen in vivo[3].
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| Cell Assay |
Apoptosis Analysis[1]
Cell Types: Hela cells Tested Concentrations: 0.01-0.1 nM Incubation Duration: 36 hrs (hours) Experimental Results: Induced cell death by apoptosis. Cell Cycle Analysis[1] Cell Types: HeLa cells Tested Concentrations: 44 hrs (hours) Incubation Duration: 0.78 nM, 1.56 nM, 3.13 nM, 6.25 nM Experimental Results: Resulted in G2/M arrest. Western Blot Analysis[3] Cell Types: Type II EOC cells Tested Concentrations: 3 μM Incubation Duration: 6 hrs (hours), 12 hrs (hours), 24 hrs (hours) Experimental Results: Induced caspase-2 activation in a time-dependent manner. Cell Cytotoxicity Assay[3] Cell Types: Type II EOC cell lines ( A2780, CP70, 01-28) Tested Concentrations: 0.003 μM, 0.03 μM, 0.3μM, 3 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: Effectively diminished cell viability in a time-dependent manner in the Type II EOC cell lines. |
| Animal Protocol |
Animal/Disease Models: Female nude mice, EOC mice xenograft model[3]
Doses: 20 mg/kg, 30 mg/kg Route of Administration: intraperitoneal (ip)injection, q4dx3 Experimental Results: Induced a decrease in tumor kinetics in a dose-dependent manner. |
| References |
|
| Molecular Formula |
C22H23F5N4O4S
|
|---|---|
| Molecular Weight |
534.499441385269
|
| Exact Mass |
534.135
|
| CAS # |
1781834-99-8
|
| Related CAS # |
Filanesib;885060-09-3
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| PubChem CID |
90488964
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| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
6
|
| Heavy Atom Count |
36
|
| Complexity |
689
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
S1C(C2C=C(C=CC=2F)F)=NN(C(N(C)OC)=O)[C@@]1(C1C=CC=CC=1)CCCN.FC(C(=O)O)(F)F
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| InChi Key |
CIJUJPVFECBUKG-BDQAORGHSA-N
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| InChi Code |
InChI=1S/C20H22F2N4O2S.C2HF3O2/c1-25(28-2)19(27)26-20(11-6-12-23,14-7-4-3-5-8-14)29-18(24-26)16-13-15(21)9-10-17(16)22;3-2(4,5)1(6)7/h3-5,7-10,13H,6,11-12,23H2,1-2H3;(H,6,7)/t20-;/m0./s1
|
| Chemical Name |
(2S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3-carboxamide;2,2,2-trifluoroacetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8709 mL | 9.3545 mL | 18.7091 mL | |
| 5 mM | 0.3742 mL | 1.8709 mL | 3.7418 mL | |
| 10 mM | 0.1871 mL | 0.9355 mL | 1.8709 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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