Filanesib
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MedKoo CAT#: 200292

CAS#: 885060-09-3 (free base)

Description: Filanesib, also known as ARRY-520, is a synthetic, small molecule targeting the kinesin spindle protein (KSP) with potential antineoplastic activity. KSP inhibitor ARRY-520 specifically inhibits KSP (kinesin-5 or Eg5), resulting in activation of the spindle assembly checkpoint, induction of cell cycle arrest during the mitotic phase, and consequently cell death in tumor cells that are actively dividing. Because KSP is not involved in postmitotic processes, such as neuronal transport, this agent does not cause the peripheral neuropathy that is often associated with tubulin-targeting agents. KSP is an ATP-dependent microtubule motor protein that is essential for the formation of bipolar spindles and the proper segregation of sister chromatids during mitosis.

Chemical Structure

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Filanesib
CAS# 885060-09-3 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200292
Name: Filanesib
CAS#: 885060-09-3 (free base)
Chemical Formula: C20H22F2N4O2S
Exact Mass: 420.14
Molecular Weight: 420.480
Elemental Analysis: C, 57.13; H, 5.27; F, 9.04; N, 13.32; O, 7.61; S, 7.6

Price and Availability

Size Price Availability Quantity
10mg USD 250 Same day
25mg USD 550 Same day
50mg USD 950 Same day
5mg USD 150 Same day
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Related CAS #: 885060-09-3 (free base), 1781834-99-8 (TFA), 885060-08-2 (R-isomer),

Synonym: ARRY-520; ARRY 520; ARRY520; Filanesib.

IUPAC/Chemical Name: (S)-2-(3-aminopropyl)-5-(2,5-difluorophenyl)-N-methoxy-N-methyl-2-phenyl-1,3,4-thiadiazole-3(2H)-carboxamide.

InChi Key: LLXISKGBWFTGEI-FQEVSTJZSA-N

InChi Code: InChI=1S/C20H22F2N4O2S/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/h3-5,7-10,13H,6,11-12,23H2,1-2H3/t20-/m0/s1

SMILES Code: O=C(N1[C@@](C2=CC=CC=C2)(CCCN)SC(C3=CC(F)=CC=C3F)=N1)N(OC)C

Appearance: white solid powder

Purity: >95% (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

Biological target: Filanesib is a kinesin spindle protein (KSP) inhibitor with an IC50 of 6 nM.
In vitro activity: Inhibition of KSP by ARRY-520 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. Furthermore, ARRY-520 increased Bim protein levels prior to caspase activation in HL-60 cells. Reference: Leukemia. 2009 Oct;23(10):1755-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593228/
In vivo activity: SCID mice implanted with HL-60 cells were treated with ARRY-520 to evaluate its effect in vivo. As shown in Figure 8A, ARRY-520 greatly decreased tumor volumes and all 5 mice showed complete responses (CR) on day 15. Although tumor growth was significantly inhibited during ARRY-520 treatment and became undetectable shortly after the treatment, tumors eventually outgrew suggesting that prolonged/repeated treatment is required to achieve better outcome. Reference: Leukemia. 2009 Oct;23(10):1755-62. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593228/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 60.0 142.69
Ethanol 20.0 47.56
DMF 20.0 47.56
PBS (pH 7.2) 0.2 0.48

Preparing Stock Solutions

The following data is based on the product molecular weight 420.480000000000000000000000000000 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. Carter BZ, Mak DH, Woessner R, Gross S, Schober WD, Estrov Z, Kantarjian H, Andreeff M. 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. doi: 10.1038/leu.2009.101. Epub 2009 May 21. PMID: 19458629; PMCID: PMC3593228. 2. 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 Nov;29(11):4373-80. PMID: 20032381.
In vitro protocol: 1. Carter BZ, Mak DH, Woessner R, Gross S, Schober WD, Estrov Z, Kantarjian H, Andreeff M. 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. doi: 10.1038/leu.2009.101. Epub 2009 May 21. PMID: 19458629; PMCID: PMC3593228. 2. 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 Nov;29(11):4373-80. PMID: 20032381.
In vivo protocol: 1. Carter BZ, Mak DH, Woessner R, Gross S, Schober WD, Estrov Z, Kantarjian H, Andreeff M. 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. doi: 10.1038/leu.2009.101. Epub 2009 May 21. PMID: 19458629; PMCID: PMC3593228. 2. 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 Nov;29(11):4373-80. PMID: 20032381.

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1: 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 Jul 15;118(14):3556-64. doi: 10.1002/cncr.26664. Epub 2011 Dec 2. PubMed PMID: 22139909. 2: Tunquist BJ, Woessner RD, Walker DH. 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. doi: 10.1158/1535-7163.MCT-10-0033. Epub 2010 Jun 22. PubMed PMID: 20571074. 3: 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 Nov;29(11):4373-80. PubMed PMID: 20032381. 4: Kim KH, Xie Y, Tytler EM, Woessner R, Mor G, Alvero AB. KSP inhibitor ARRY-520 as a substitute for Paclitaxel in Type I ovarian cancer cells. J Transl Med. 2009 Jul 20;7:63. doi: 10.1186/1479-5876-7-63. PubMed PMID: 19619321; PubMed Central PMCID: PMC2719595. 5: Carter BZ, Mak DH, Woessner R, Gross S, Schober WD, Estrov Z, Kantarjian H, Andreeff M. 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. doi: 10.1038/leu.2009.101. Epub 2009 May 21. PubMed PMID: 19458629; PubMed Central PMCID: PMC3593228.