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MedKoo Cat#: 200292 | Name: Filanesib
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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

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

Theoretical Analysis

MedKoo Cat#: 200292

Name: Filanesib

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

Chemical Formula: C20H22F2N4O2S

Exact Mass: 420.1432

Molecular Weight: 420.48

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
5mg USD 110.00 Ready to ship
10mg USD 200.00 Ready to ship
25mg USD 450.00 Ready to ship
50mg USD 800.00 Ready to ship
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Related CAS #
885060-09-3 (free base) 1781834-99-8 (TFA) 885060-08-2 (R-isomer) 1385020-40-5 (HCl)
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
More Info
In preclinical studies of multiple myeloma, ARRY-520 monotherapy has superior anti-tumor activity compared to Velcade® (bortezomib) or Revlimid® (lenalidomide). Also, ARRY-520 combined with Velcade, including bortezomib-refractory models, showed synergistic activity in vivo and superadditive activity when combined with Revlimid. Apoptosis in myeloma cells treated with ARRY-520 requires loss of the short-lived survival protein Mcl-1, providing a likely mechanistic explanation for ARRY-520 activity. Further studies, including a single-agent Phase 2 study and combination trials in multiple myeloma, are planned. ARRY-520 inhibits kinesin spindle protein, or KSP, which plays an essential role in mitotic spindle formation. Like taxanes and vinca alkaloids, KSP inhibitors inhibit tumor growth by preventing mitotic spindle formation and cell division. However, unlike taxanes and vinca alkaloids, KSP inhibitors do not demonstrate certain side effects such as peripheral neuropathy and alopecia. ARRY-520 has demonstrated efficacy in preclinical hematological tumor models, with a 100.0% complete response rate observed in models of acute myeloid leukemia, or AML, and multiple myeloma, or MM. Treatment of MM models with ARRY-520 resulted in significant regression of tumors that had previously progressed after treatment with Velcade_ (bortezomib) or Revlimid_ (lenalidomide). In addition, ARRY-520 retained activity in a wide range of tumors resistant to other molecules with different mechanisms of action, such as the taxanes. Examination of pharmacodynamic activity in preclinical models reinforced that hematological cancers were among the most sensitive to ARRY-520. (Source: http://www.arraybiopharma.com/ProductPipeline/Cancer/KSP.asp).   On June 05, 2010, Array BioPharma Inc. announced the presentation of positive Phase 1 clinical data for its novel kinesin spindle protein (KSP) inhibitor, ARRY-520. The data, which were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, indicate that ARRY-520 was well tolerated and has shown encouraging preliminary results in the treatment of multiple myeloma. ARRY-520 is a novel, first-in-class, highly potent, selective KSP inhibitor currently advancing into a single-agent Phase 2 clinical trial and combination trials in patients with multiple myeloma.       
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/
Solvent mg/mL 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
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 420.48 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.
1: Algarín EM, Hernández-García S, Garayoa M, Ocio EM. Filanesib for the treatment of multiple myeloma. Expert Opin Investig Drugs. 2020 Jan;29(1):5-14. doi: 10.1080/13543784.2020.1703179. Epub 2019 Dec 12. PMID: 31815551. 2: Pan D, Kaufman JL, Htut M, Agrawal M, Mazumder A, Cornell RF, Zonder JA, Fay JW, Modiano MR, Moshier EL, Rush SA, Tunquist BJ, Chari A. Filanesib plus bortezomib and dexamethasone in relapsed/refractory t(11;14) and 1q21 gain multiple myeloma. Cancer Med. 2022 Jan;11(2):358-370. doi: 10.1002/cam4.4451. Epub 2021 Dec 17. PMID: 34921527; PMCID: PMC8729045. 3: Jungwirth G, Yu T, Cao J, Eddine MA, Moustafa M, Warta R, Debus J, Unterberg A, Abdollahi A, Herold-Mende C. KIF11 inhibitors filanesib and ispinesib inhibit meningioma growth in vitro and in vivo. Cancer Lett. 2021 May 28;506:1-10. doi: 10.1016/j.canlet.2021.02.016. Epub 2021 Feb 27. PMID: 33652084. 4: Ocio EM, Motlló C, Rodríguez-Otero P, Martínez-López J, Cejalvo MJ, Martín- Sánchez J, Bladé J, García-Malo MD, Dourdil MV, García-Mateo A, de Arriba F, García-Sanz R, de la Rubia J, Oriol A, Lahuerta JJ, San-Miguel JF, Mateos MV. Filanesib in combination with pomalidomide and dexamethasone in refractory MM patients: safety and efficacy, and association with alpha 1-acid glycoprotein (AAG) levels. Phase Ib/II Pomdefil clinical trial conducted by the Spanish MM group. Br J Haematol. 2021 Feb;192(3):522-530. doi: 10.1111/bjh.16788. Epub 2020 Jun 5. PMID: 32501528. 5: Hernández-García S, San-Segundo L, González-Méndez L, Corchete LA, Misiewicz- Krzeminska I, Martín-Sánchez M, López-Iglesias AA, Algarín EM, Mogollón P, Díaz- Tejedor A, Paíno T, Tunquist B, Mateos MV, Gutiérrez NC, Díaz-Rodriguez E, Garayoa M, Ocio EM. The kinesin spindle protein inhibitor filanesib enhances the activity of pomalidomide and dexamethasone in multiple myeloma. Haematologica. 2017 Dec;102(12):2113-2124. doi: 10.3324/haematol.2017.168666. Epub 2017 Aug 31. PMID: 28860344; PMCID: PMC5709111. 6: Lee HC, Shah JJ, Feng L, Manasanch EE, Lu R, Morphey A, Crumpton B, Patel KK, Wang ML, Alexanian R, Thomas SK, Weber DM, Orlowski RZ. A phase 1 study of filanesib, carfilzomib, and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Blood Cancer J. 2019 Oct 1;9(10):80. doi: 10.1038/s41408-019-0240-6. PMID: 31575851; PMCID: PMC6773683. 7: LoRusso PM, Goncalves PH, Casetta L, Carter JA, Litwiler K, Roseberry D, Rush S, Schreiber J, Simmons HM, Ptaszynski M, Sausville EA. First-in-human phase 1 study of filanesib (ARRY-520), a kinesin spindle protein inhibitor, in patients with advanced solid tumors. Invest New Drugs. 2015 Apr;33(2):440-9. doi: 10.1007/s10637-015-0211-0. Epub 2015 Feb 17. PMID: 25684345. 8: Shah JJ, Kaufman JL, Zonder JA, Cohen AD, Bensinger WI, Hilder BW, Rush SA, Walker DH, Tunquist BJ, Litwiler KS, Ptaszynski M, Orlowski RZ, Lonial S. A Phase 1 and 2 study of Filanesib alone and in combination with low-dose dexamethasone in relapsed/refractory multiple myeloma. Cancer. 2017 Dec 1;123(23):4617-4630. doi: 10.1002/cncr.30892. Epub 2017 Aug 17. PMID: 28817190; PMCID: PMC5856158. 9: Norris EJ, DeStephanis D, Tunquist B, Usmani S, Ganapathi R, Ganapathi M. Cytotoxic efficacy of filanesib and melphalan combination is governed by sequence of treatment in human myeloma cells. Blood Cancer J. 2016 Oct 7;6(10):e480. doi: 10.1038/bcj.2016.92. PMID: 27716742; PMCID: PMC5098264. 10: Chari A, Htut M, Zonder JA, Fay JW, Jakubowiak AJ, Levy JB, Lau K, Burt SM, Tunquist BJ, Hilder BW, Rush SA, Walker DH, Ptaszynski M, Kaufman JL. A phase 1 dose-escalation study of filanesib plus bortezomib and dexamethasone in patients with recurrent/refractory multiple myeloma. Cancer. 2016 Nov 15;122(21):3327-3335. doi: 10.1002/cncr.30174. Epub 2016 Jul 19. PMID: 27433944; PMCID: PMC6857452. 11: Naymagon L, Abdul-Hay M. Novel agents in the treatment of multiple myeloma: a review about the future. J Hematol Oncol. 2016 Jun 30;9(1):52. doi: 10.1186/s13045-016-0282-1. PMID: 27363832; PMCID: PMC4929712. 12: Rajan AM, Kumar S. New investigational drugs with single-agent activity in multiple myeloma. Blood Cancer J. 2016 Jul 29;6(7):e451. doi: 10.1038/bcj.2016.53. PMID: 27471867; PMCID: PMC5030378. 13: Chamariya R, Suvarna V. Role of KSP Inhibitors as Anti-cancer Therapeutics: An Update. Anticancer Agents Med Chem. 2022;22(14):2517-2538. doi: 10.2174/1871520622666220119093105. PMID: 35043768. 14: Zhang K, Desai A, Zeng D, Gong T, Lu P, Wang M. Magic year for multiple myeloma therapeutics: Key takeaways from the ASH 2015 annual meeting. Oncotarget. 2017 Feb 7;8(6):10748-10759. doi: 10.18632/oncotarget.13314. PMID: 27863374; PMCID: PMC5354697. 15: D'Agostino M, Salvini M, Palumbo A, Larocca A, Gay F. Novel investigational drugs active as single agents in multiple myeloma. Expert Opin Investig Drugs. 2017 Jun;26(6):699-711. doi: 10.1080/13543784.2017.1324571. Epub 2017 May 8. PMID: 28448171. 16: Garcia-Saez I, Skoufias DA. Eg5 targeting agents: From new anti-mitotic based inhibitor discovery to cancer therapy and resistance. Biochem Pharmacol. 2021 Feb;184:114364. doi: 10.1016/j.bcp.2020.114364. Epub 2020 Dec 11. PMID: 33310050. 17: Shahin R, Aljamal S. Kinesin spindle protein inhibitors in cancer: from high throughput screening to novel therapeutic strategies. Future Sci OA. 2022 Feb 21;8(3):FSO778. doi: 10.2144/fsoa-2021-0116. PMID: 35251692; PMCID: PMC8890118. 18: Chen GY, Kang YJ, Gayek AS, Youyen W, Tüzel E, Ohi R, Hancock WO. Eg5 Inhibitors Have Contrasting Effects on Microtubule Stability and Metaphase Spindle Integrity. ACS Chem Biol. 2017 Apr 21;12(4):1038-1046. doi: 10.1021/acschembio.6b01040. Epub 2017 Feb 22. PMID: 28165699; PMCID: PMC5515541. 19: Milic B, Chakraborty A, Han K, Bassik MC, Block SM. KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics. Proc Natl Acad Sci U S A. 2018 May 15;115(20):E4613-E4622. doi: 10.1073/pnas.1801242115. Epub 2018 Apr 27. PMID: 29703754; PMCID: PMC5960320. 20: Owens B. Kinesin inhibitor marches toward first-in-class pivotal trial. Nat Med. 2013 Dec;19(12):1550. doi: 10.1038/nm1213-1550a. PMID: 24309639.