Tozasertib (VX-680)

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MedKoo CAT#: 201900

CAS#: 639089-54-6

Description: Tozasertib, also known as VX-680, MK0457 or VE465, is a synthetic, small-molecule Aurora kinase inhibitor with potential antitumor activity. Tozasertib binds to and inhibits Aurora kinases (AKs), thereby inducing apoptosis in tumor cells in which AKs are overexpressed. AKs, a family of serine-threonine kinases, are essential for mitotic progression, spindle formation, centrosome maturation, chromosomal segregation, and cytokinesis.

Chemical Structure

Tozasertib (VX-680)
CAS# 639089-54-6

Theoretical Analysis

MedKoo Cat#: 201900
Name: Tozasertib (VX-680)
CAS#: 639089-54-6
Chemical Formula: C23H28N8OS
Exact Mass: 464.21068
Molecular Weight: 464.59
Elemental Analysis: C, 59.46; H, 6.07; N, 24.12; O, 3.44; S, 6.90

Price and Availability

Size Price Availability Quantity
100.0mg USD 150.0 Same day
200.0mg USD 250.0 Same day
500.0mg USD 450.0 Same day
1.0g USD 750.0 Same day
2.0g USD 1250.0 Same day
5.0g USD 2150.0 2 Weeks
10.0g USD 3850.0 2 Weeks
20.0g USD 6950.0 2 Weeks
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Synonym: VX680; VX 680; VX-680; MK0457; MK 0457; MK-0457; VE465; VE-465; VE 465; Tozasertib

IUPAC/Chemical Name: (N-[4({4-(4-methylpiperazin-1-yl)-6-[(3-methyl-1H-pyrazol-5 -yl)amino]pyrimidin-2-yl}thio)phenyl]cyclopropanecarboxamide)


InChi Code: InChI=1S/C23H28N8OS/c1-15-13-20(29-28-15)25-19-14-21(31-11-9-30(2)10-12-31)27-23(26-19)33-18-7-5-17(6-8-18)24-22(32)16-3-4-16/h5-8,13-14,16H,3-4,9-12H2,1-2H3,(H,24,32)(H2,25,26,27,28,29)


Appearance: white solid powder

Purity: >98% (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: Tozasertib (VX 680; MK-0457) is an inhibitor of Aurora A/B/C kinases with Kis of 0.6, 18, 4.6 nM, respectively.
In vitro activity: Tozasertib inhibited the release of β‐hexosaminidase and histamine in BMMCs (bone marrow-derived mast cells) activated with IgE/Ag stimulation in a concentration‐dependent manner (Figure 3b,c). Western blot analyses of signal pathway molecules showed that tozasertib pretreatment inhibited activation of NF‐κB and MAPKs (p38, JNK, and ERK) in BMMCs, as shown by decreased levels of p‐p38, p‐JNK, p‐ERK1/2, p‐p65, and IκBα (Figure 3d,e). The effects of tozasertib on NF‐κB and MAPK signalling molecules exhibited concentration‐dependence in IgE/Ag‐stimulated BMMCs. These results indicated that tozasertib suppressed activation of IgE/Ag‐stimulated BMMCs through down‐regulation of NF‐κB and MAPK pathways. Reference: Br J Pharmacol. 2020 Jun;177(12):2848-2859.
In vivo activity: PCA (passive cutaneous anaphylaxis) was used in mouse ears to evaluate tozasertib effects on anaphylaxis in vivo. When ears were injected with 4% Evans blue dye mixed with Ag in PCA tests, tozasertib reduced allergic responses in DNP‐HSA‐sensitized PCA mice, compared with the PBS‐injected control group, as shown by decreased Evans blue dye density in the injected ear (Figure 4a), decreased ear thickness (Figure 4b,c), and diminished extrusion of dye from the injected ear (Figure 4d). Reference: Br J Pharmacol. 2020 Jun;177(12):2848-2859.

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
DMSO 71.56 154.03
DMF 20.0 43.05
DMF:PBS (pH 7) (1:10) 0.1 21.52

Preparing Stock Solutions

The following data is based on the product molecular weight 464.59 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. Zhang LN, Ji K, Sun YT, Hou YB, Chen JJ. Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo. Br J Pharmacol. 2020 Jun;177(12):2848-2859. doi: 10.1111/bph.15012. Epub 2020 Apr 6. PMID: 32017040; PMCID: PMC7236079.
In vitro protocol: 1. Zhang LN, Ji K, Sun YT, Hou YB, Chen JJ. Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo. Br J Pharmacol. 2020 Jun;177(12):2848-2859. doi: 10.1111/bph.15012. Epub 2020 Apr 6. PMID: 32017040; PMCID: PMC7236079.
In vivo protocol: 1. Zhang LN, Ji K, Sun YT, Hou YB, Chen JJ. Aurora kinase inhibitor tozasertib suppresses mast cell activation in vitro and in vivo. Br J Pharmacol. 2020 Jun;177(12):2848-2859. doi: 10.1111/bph.15012. Epub 2020 Apr 6. PMID: 32017040; PMCID: PMC7236079.

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1: Elkins JM, Santaguida S, Musacchio A, Knapp S. Crystal structure of human aurora B in complex with INCENP and VX-680. J Med Chem. 2012 Sep 13;55(17):7841-8. doi: 10.1021/jm3008954. Epub 2012 Sep 4. PubMed PMID: 22920039; PubMed Central PMCID: PMC3621106.

2: Dewerth A, Wonner T, Lieber J, Ellerkamp V, Warmann SW, Fuchs J, Armeanu-Ebinger S. In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma. Pediatr Surg Int. 2012 Jun;28(6):579-89. doi: 10.1007/s00383-012-3086-6. Epub 2012 Apr 18. PubMed PMID: 22526548.

3: Salah E, Ugochukwu E, Barr AJ, von Delft F, Knapp S, Elkins JM. Crystal structures of ABL-related gene (ABL2) in complex with imatinib, tozasertib (VX-680), and a type I inhibitor of the triazole carbothioamide class. J Med Chem. 2011 Apr 14;54(7):2359-67. doi: 10.1021/jm101506n. Epub 2011 Mar 18. PubMed PMID: 21417343; PubMed Central PMCID: PMC3075623.

4: Rao B, van Leeuwen IM, Higgins M, Campbel J, Thompson AM, Lane DP, Lain S. Evaluation of an Actinomycin D/VX-680 aurora kinase inhibitor combination in p53-based cyclotherapy. Oncotarget. 2010 Nov;1(7):639-50. PubMed PMID: 21317459; PubMed Central PMCID: PMC3248124.

5: Fei F, Stoddart S, Groffen J, Heisterkamp N. Activity of the Aurora kinase inhibitor VX-680 against Bcr/Abl-positive acute lymphoblastic leukemias. Mol Cancer Ther. 2010 May;9(5):1318-27. doi: 10.1158/1535-7163.MCT-10-0069. Epub 2010 Apr 13. PubMed PMID: 20388735; PubMed Central PMCID: PMC2868097.

6: Cheok CF, Kua N, Kaldis P, Lane DP. Combination of nutlin-3 and VX-680 selectively targets p53 mutant cells with reversible effects on cells expressing wild-type p53. Cell Death Differ. 2010 Sep;17(9):1486-500. doi: 10.1038/cdd.2010.18. Epub 2010 Mar 5. PubMed PMID: 20203688.

7: Donato NJ, Fang D, Sun H, Giannola D, Peterson LF, Talpaz M. Targets and effectors of the cellular response to aurora kinase inhibitor MK-0457 (VX-680) in imatinib sensitive and resistant chronic myelogenous leukemia. Biochem Pharmacol. 2010 Mar 1;79(5):688-97. doi: 10.1016/j.bcp.2009.10.009. Epub 2009 Oct 27. PubMed PMID: 19874801.

8: Bebbington D, Binch H, Charrier JD, Everitt S, Fraysse D, Golec J, Kay D, Knegtel R, Mak C, Mazzei F, Miller A, Mortimore M, O'Donnell M, Patel S, Pierard F, Pinder J, Pollard J, Ramaya S, Robinson D, Rutherford A, Studley J, Westcott J. The discovery of the potent aurora inhibitor MK-0457 (VX-680). Bioorg Med Chem Lett. 2009 Jul 1;19(13):3586-92. doi: 10.1016/j.bmcl.2009.04.136. Epub 2009 May 3. PubMed PMID: 19447622.

9: Fiskus W, Wang Y, Joshi R, Rao R, Yang Y, Chen J, Kolhe R, Balusu R, Eaton K, Lee P, Ustun C, Jillella A, Buser CA, Peiper S, Bhalla K. Cotreatment with vorinostat enhances activity of MK-0457 (VX-680) against acute and chronic myelogenous leukemia cells. Clin Cancer Res. 2008 Oct 1;14(19):6106-15. doi: 10.1158/1078-0432.CCR-08-0721. PubMed PMID: 18829489; PubMed Central PMCID: PMC2665710.

10: Zhao B, Smallwood A, Yang J, Koretke K, Nurse K, Calamari A, Kirkpatrick RB, Lai Z. Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2. Protein Sci. 2008 Oct;17(10):1791-7. doi: 10.1110/ps.036590.108. Epub 2008 Jul 28. PubMed PMID: 18662907; PubMed Central PMCID: PMC2548374.

11: Arlot-Bonnemains Y, Baldini E, Martin B, Delcros JG, Toller M, Curcio F, Ambesi-Impiombato FS, D'Armiento M, Ulisse S. Effects of the Aurora kinase inhibitor VX-680 on anaplastic thyroid cancer-derived cell lines. Endocr Relat Cancer. 2008 Jun;15(2):559-68. doi: 10.1677/ERC-08-0021. Epub 2008 Apr 22. PubMed PMID: 18430894.

12: Huang XF, Luo SK, Xu J, Li J, Xu DR, Wang LH, Yan M, Wang XR, Wan XB, Zheng FM, Zeng YX, Liu Q. Aurora kinase inhibitory VX-680 increases Bax/Bcl-2 ratio and induces apoptosis in Aurora-A-high acute myeloid leukemia. Blood. 2008 Mar 1;111(5):2854-65. Epub 2007 Dec 26. PubMed PMID: 18160664.

13: Tyler RK, Shpiro N, Marquez R, Eyers PA. VX-680 inhibits Aurora A and Aurora B kinase activity in human cells. Cell Cycle. 2007 Nov 15;6(22):2846-54. Epub 2007 Aug 27. PubMed PMID: 18032922.

14: Cheetham GM, Charlton PA, Golec JM, Pollard JR. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett. 2007 Jun 28;251(2):323-9. Epub 2007 Jan 19. PubMed PMID: 17240048.

15: Gizatullin F, Yao Y, Kung V, Harding MW, Loda M, Shapiro GI. The Aurora kinase inhibitor VX-680 induces endoreduplication and apoptosis preferentially in cells with compromised p53-dependent postmitotic checkpoint function. Cancer Res. 2006 Aug 1;66(15):7668-77. PubMed PMID: 16885368.

16: Young MA, Shah NP, Chao LH, Seeliger M, Milanov ZV, Biggs WH 3rd, Treiber DK, Patel HK, Zarrinkar PP, Lockhart DJ, Sawyers CL, Kuriyan J. Structure of the kinase domain of an imatinib-resistant Abl mutant in complex with the Aurora kinase inhibitor VX-680. Cancer Res. 2006 Jan 15;66(2):1007-14. PubMed PMID: 16424036.

17: Harrington EA, Bebbington D, Moore J, Rasmussen RK, Ajose-Adeogun AO, Nakayama T, Graham JA, Demur C, Hercend T, Diu-Hercend A, Su M, Golec JM, Miller KM. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med. 2004 Mar;10(3):262-7. Epub 2004 Feb 22. Erratum in: Nat Med. 2007 Apr;13(4):511. PubMed PMID: 14981513.

Additional Information

According CNBC news  published on 20 Nov, 2007, Vertex Pharmaceuticals said Merck & Co halted enrollment on trials of their investigational leukemia drug MK-0457 due to a potential heart safety issue in one patient. They suspended trials involving MK-0457, also known as VX-680, pending a full analysis of efficacy and safety data after preliminary data showed that one patient experienced QTc prolongation. The companies also said they discontinued development of their Aurora kinase inhibitor MK-6592, or VX-667, after the investigational drug failed to meet pharmacokinetic objectives in a Phase 1 trial.