Back to products

Browse products

Approved anticancer agents

Anticancer agents in trials

Anticancer agents in preclinical trials

Anticancer molecular libraries

MedKoo product information:

Belinostat

Belinostat is a novel hydroxamic acid-type histone deacetylase (HDAC) inhibitor with antineoplastic activity. Belinostat targets HDAC enzymes, thereby inhibiting tumor cell proliferation, inducing apoptosis, promoting cellular differentiation, and inhibiting angiogenesis. This agent may sensitize drug-resistant tumor cells to other antineoplastic agents, possibly through a mechanism involving the down-regulation of thymidylate synthase. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus).

Current developer:   TopoTarget A/S.

According to http://www.topotarget.com/index.dsp?area=272; Belinostat (PXD 101) is in late stage clinical development with more than 600 patients treated. Belinostat is well tolerated which allows combination with traditional chemotherapy without causing further bone marrow toxicity. In pre-clinical trials belinostat has shown to be effective against multiple cancers by inhibiting cell proliferation (the cancer is prevented from growing) and inducing programmed cell death (“apoptosis”) in tumour cells (the tumour cells are forced to self-destruct). Belinostat has been tested in a number of Phase I/II clinical trials in haematological cancers and solid tumours. Data from these trials has provided proof for the anti-tumour effect of belinostat as monotherapy in two types of T-cell lymphomas (PTCL and CTCL) and in thymoma, and have demonstrated that belinostat has beneficial effects in combination with other anti-cancer drugs for the treatment of multiple types of cancer including ovarian cancer, CUP, multiple myeloma, acute myeloid leukaemia and bladder cancer.

1: Gravina GL, Marampon F, Giusti I, Carosa E, Di Sante S, Ricevuto E, Dolo V, Tombolini V, Jannini EA, Festuccia C. Differential effects of PXD101 (belinostat) on androgen-dependent and androgen-independent prostate cancer models. Int J Oncol. 2012 Mar;40(3):711-20. doi: 10.3892/ijo.2011.1270. Epub 2011 Nov 23. PubMed PMID: 22134754.

2: Molife LR, de Bono JS. Belinostat: clinical applications in solid tumors and lymphoma. Expert Opin Investig Drugs. 2011 Dec;20(12):1723-32. Epub 2011 Nov 3. PubMed PMID: 22046971.

3: Chowdhury S, Howell GM, Teggart CA, Chowdhury A, Person JJ, Bowers DM, Brattain MG. Histone deacetylase inhibitor belinostat represses survivin expression through reactivation of transforming growth factor beta (TGFbeta) receptor II leading to cancer cell death. J Biol Chem. 2011 Sep 2;286(35):30937-48. Epub 2011 Jul 8. PubMed PMID: 21757750; PubMed Central PMCID: PMC3162453.

4: Cashen A, Juckett M, Jumonville A, Litzow M, Flynn PJ, Eckardt J, Laplant B, Laumann K, Erlichman C, Dipersio J. Phase II study of the histone deacetylase inhibitor belinostat (PXD101) for the treatment of myelodysplastic syndrome (MDS). Ann Hematol. 2012 Jan;91(1):33-8. Epub 2011 May 3. PubMed PMID: 21538061.

5: Giaccone G, Rajan A, Berman A, Kelly RJ, Szabo E, Lopez-Chavez A, Trepel J, Lee MJ, Cao L, Espinoza-Delgado I, Spittler J, Loehrer PJ Sr. Phase II study of belinostat in patients with recurrent or refractory advanced thymic epithelial tumors. J Clin Oncol. 2011 May 20;29(15):2052-9. Epub 2011 Apr 18. PubMed PMID: 21502553; PubMed Central PMCID: PMC3107761.

6: Dai Y, Chen S, Wang L, Pei XY, Kramer LB, Dent P, Grant S. Bortezomib interacts synergistically with belinostat in human acute myeloid leukaemia and acute lymphoblastic leukaemia cells in association with perturbation in NF-κB and Bim. Br J Haematol. 2011 Mar 6. doi: 10.1111/j.1365-2141.2011.08591.x. [Epub ahead of print] PubMed PMID: 21375523.

7: Wang LZ, Chan D, Yeo W, Wan SC, Chan S, Chan A, Lee SC, Lee HS, Goh BC. A sensitive and specific liquid chromatography-tandem mass spectrometric method for determination of belinostat in plasma from liver cancer patients. J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Sep 15;878(26):2409-14. Epub 2010 Jul 30. PubMed PMID: 20724229.

8: Beck HC, Petersen J, Nielsen SJ, Morsczeck C, Jensen PB, Sehested M, Grauslund M. Proteomic profiling of human colon cancer cells treated with the histone deacetylase inhibitor belinostat. Electrophoresis. 2010 Aug;31(16):2714-21. Erratum in: Electrophoresis. 2010 Oct;31(21):3619. Morszeck, Christian [corrected to Morsczeck, Christian]. PubMed PMID: 20717991.

9: Steele NL, Plumb JA, Vidal L, Tjørnelund J, Knoblauch P, Buhl-Jensen P, Molife R, Brown R, de Bono JS, Evans TR. Pharmacokinetic and pharmacodynamic properties of an oral formulation of the histone deacetylase inhibitor Belinostat (PXD101). Cancer Chemother Pharmacol. 2011 Jun;67(6):1273-9. Epub 2010 Aug 13. PubMed PMID: 20706839.

10: Lassen U, Molife LR, Sorensen M, Engelholm SA, Vidal L, Sinha R, Penson RT, Buhl-Jensen P, Crowley E, Tjornelund J, Knoblauch P, de Bono JS. A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours. Br J Cancer. 2010 Jun 29;103(1):12-7. Epub 2010 Jun 15. PubMed PMID: 20588278; PubMed Central PMCID: PMC2905291.

11: Mackay HJ, Hirte H, Colgan T, Covens A, MacAlpine K, Grenci P, Wang L, Mason J, Pham PA, Tsao MS, Pan J, Zwiebel J, Oza AM. Phase II trial of the histone deacetylase inhibitor belinostat in women with platinum resistant epithelial ovarian cancer and micropapillary (LMP) ovarian tumours. Eur J Cancer. 2010 Jun;46(9):1573-9. Epub 2010 Mar 19. PubMed PMID: 20304628; PubMed Central PMCID: PMC3244274.

12: Paoluzzi L, Scotto L, Marchi E, Zain J, Seshan VE, O'Connor OA. Romidepsin and belinostat synergize the antineoplastic effect of bortezomib in mantle cell lymphoma. Clin Cancer Res. 2010 Jan 15;16(2):554-65. Epub 2010 Jan 12. PubMed PMID: 20068080.

13: Monks A, Hose CD, Pezzoli P, Kondapaka S, Vansant G, Petersen KD, Sehested M, Monforte J, Shoemaker RH. Gene expression-signature of belinostat in cell lines is specific for histone deacetylase inhibitor treatment, with a corresponding signature in xenografts. Anticancer Drugs. 2009 Sep;20(8):682-92. PubMed PMID: 19606018.

14: Gimsing P. Belinostat: a new broad acting antineoplastic histone deacetylase inhibitor. Expert Opin Investig Drugs. 2009 Apr;18(4):501-8. Erratum in: Expert Opin Investig Drugs. 2009 Jun;18(6):873. PubMed PMID: 19335278.

15: Ma BB, Sung F, Tao Q, Poon FF, Lui VW, Yeo W, Chan SL, Chan AT. The preclinical activity of the histone deacetylase inhibitor PXD101 (belinostat) in hepatocellular carcinoma cell lines. Invest New Drugs. 2010 Apr;28(2):107-14. Epub 2009 Jan 27. PubMed PMID: 19172229.

16: Ramalingam SS, Belani CP, Ruel C, Frankel P, Gitlitz B, Koczywas M, Espinoza-Delgado I, Gandara D. Phase II study of belinostat (PXD101), a histone deacetylase inhibitor, for second line therapy of advanced malignant pleural mesothelioma. J Thorac Oncol. 2009 Jan;4(1):97-101. PubMed PMID: 19096314; PubMed Central PMCID: PMC3263397.

17: Kapoor S. Inhibition of HDAC6-dependent carcinogenesis: emerging, new therapeutic options besides belinostat. Int J Cancer. 2009 Jan 15;124(2):509. PubMed PMID: 18942705.

18: Dejligbjerg M, Grauslund M, Litman T, Collins L, Qian X, Jeffers M, Lichenstein H, Jensen PB, Sehested M. Differential effects of class I isoform histone deacetylase depletion and enzymatic inhibition by belinostat or valproic acid in HeLa cells. Mol Cancer. 2008 Sep 12;7:70. PubMed PMID: 18789133; PubMed Central PMCID: PMC2553797.

19: Gimsing P, Hansen M, Knudsen LM, Knoblauch P, Christensen IJ, Ooi CE, Buhl-Jensen P. A phase I clinical trial of the histone deacetylase inhibitor belinostat in patients with advanced hematological neoplasia. Eur J Haematol. 2008 Sep;81(3):170-6. Epub 2008 May 27. PubMed PMID: 18510700.

20: Dejligbjerg M, Grauslund M, Christensen IJ, Tjørnelund J, Buhl Jensen P, Sehested M. Identification of predictive biomarkers for the histone deacetylase inhibitor belinostat in a panel of human cancer cell lines. Cancer Biomark. 2008;4(2):101-9. PubMed PMID: 18503161.

21: Marquard L, Petersen KD, Persson M, Hoff KD, Jensen PB, Sehested M. Monitoring the effect of belinostat in solid tumors by H4 acetylation. APMIS. 2008 May;116(5):382-92. PubMed PMID: 18452428; PubMed Central PMCID: PMC2774150.

22: Steele NL, Plumb JA, Vidal L, Tjørnelund J, Knoblauch P, Rasmussen A, Ooi CE, Buhl-Jensen P, Brown R, Evans TR, DeBono JS. A phase 1 pharmacokinetic and pharmacodynamic study of the histone deacetylase inhibitor belinostat in patients with advanced solid tumors. Clin Cancer Res. 2008 Feb 1;14(3):804-10. PubMed PMID: 18245542.

23: Dai Y, Chen S, Kramer LB, Funk VL, Dent P, Grant S. Interactions between bortezomib and romidepsin and belinostat in chronic lymphocytic leukemia cells. Clin Cancer Res. 2008 Jan 15;14(2):549-58. PubMed PMID: 18223231.

24: Qian X, Ara G, Mills E, LaRochelle WJ, Lichenstein HS, Jeffers M. Activity of the histone deacetylase inhibitor belinostat (PXD101) in preclinical models of prostate cancer. Int J Cancer. 2008 Mar 15;122(6):1400-10. PubMed PMID: 18027850.

25: Warren KE, McCully C, Dvinge H, Tjørnelund J, Sehested M, Lichenstein HS, Balis FM. Plasma and cerebrospinal fluid pharmacokinetics of the histone deacetylase inhibitor, belinostat (PXD101), in non-human primates. Cancer Chemother Pharmacol. 2008 Aug;62(3):433-7. Epub 2007 Oct 25. PubMed PMID: 17960383.

26: Buckley MT, Yoon J, Yee H, Chiriboga L, Liebes L, Ara G, Qian X, Bajorin DF, Sun TT, Wu XR, Osman I. The histone deacetylase inhibitor belinostat (PXD101) suppresses bladder cancer cell growth in vitro and in vivo. J Transl Med. 2007 Oct 12;5:49. PubMed PMID: 17935615; PubMed Central PMCID: PMC2100044.