WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 200460
Description: 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. Belinostat was approved in 2014 for relapsed or refractory peripheral T-cell lymphoma.
MedKoo Cat#: 200460
Chemical Formula: C15H14N2O4S
Exact Mass: 318.06743
Molecular Weight: 318.34
Elemental Analysis: C, 56.59; H, 4.43; N, 8.80; O, 20.10; S, 10.07.
Related CAS #: 866323-14-0 414864-00-9
Synonym: PXD 101; PXD101; PXD-101; PX105684; PX-105684; PX 105684; NSC726630; brand name: Beleodaq.
IUPAC/Chemical Name: (E)-N-hydroxy-3-[3-(phenylsulfamoyl)phenyl]prop-2-enamide.
InChi Key: NCNRHFGMJRPRSK-MDZDMXLPSA-N
InChi Code: InChI=1S/C15H14N2O4S/c18-15(16-19)10-9-12-5-4-8-14(11-12)22(20,21)17-13-6-2-1-3-7-13/h1-11,17,19H,(H,16,18)/b10-9+
SMILES Code: O=C(NO)/C=C/C1=CC=CC(S(=O)(NC2=CC=CC=C2)=O)=C1
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: 2934.99.03.00
|Biological target:||Belinostat (PXD101; PX105684) is a potent HDAC inhibitor with an IC50 of 27 nM in HeLa cell extracts.|
|In vitro activity:||PXD101 inhibited the growth of a number of human tumor cell lines in vitro with IC50s determined by a clonogenic assay in the range 0.2–3.4 μm (Table 1). There was no effect on colony size. Sensitivity to PXD101 is not related to the total HDAC activity of the cell line or inhibition of this activity in the cell lysate. There was no correlation between sensitivity to PXD101 and sensitivity to a DNA-damaging agent, such as cisplatin (r2 = 0.01). The cisplatin- (A2780/cp70) and doxorubicin (2780AD, p-glycoprotein positive)-resistant derivatives of the human ovarian tumor cell line A2780 showed low fold cross-resistance to PXD101. PXD101 induced apoptosis as determined by measurement of PARP cleavage after drug incubation for 24 h (Fig. 3a). PARP cleavage was detected in all cell lines examined except for PC3 and 2780AD (Fig. 3a). Interestingly, these two cell lines are not the most resistant to PXD101, and the lines did not show PARP cleavage when incubated with the DNA-damaging agent cisplatin (50 μm; data not shown). The colon tumor cell line HCT116 was markedly sensitive to induction of PARP cleavage, which was observed after drug incubation for between 18 and 24 h and at a PXD101 concentration as low as 0.16 μm (Fig. 3b). Acetylation of histones H3 and H4 was also clearly apparent after incubation for 1 h with PXD101 at these concentrations. Reference: Mol Cancer Ther. 2003 Aug;2(8):721-8. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12939461|
|In vivo activity:||Tumor-bearing mice were treated i.p. with PXD101 once daily for 7 days. Significant (P < 0.01) growth delay was observed at a dose of 10 mg/kg/day in xenografts of A2780 (Fig. 4a) and in the cisplatin derivative (A2780/cp70; Fig. 4c). For both tumors, growth delay increased with increasing dose of PXD101 up to a dose of 40 mg/kg/day. Drug treatment had no effect on the body weight of the mice (Fig. 4b), and there were no apparent signs of toxicity to the mice. Growth inhibition was also observed in xenografts of the human colon tumor cell line HCT116 (Fig. 4d). Acetylated histone H4 was detected in peripheral blood mononuclear cells at 1 and 2 h after a single i.p. injection of PXD101 (40 mg/kg) to A2780 tumor-bearing mice and had returned to baseline levels by 3 h (Fig. 5a). This effect of PXD101 on histone acetylation was dose dependent with marked acetylation apparent at doses of ≥10 mg/kg in both peripheral blood mononuclear cells (blood) and tumor (Fig. 5b). Plasma drug concentrations were determined at 0.5 and 2 h after a single i.p. injection of PXD101 (20 mg/kg) in mice. At 0.5 h, the mean drug concentration was 3.3 ± 0.7 μm (n = 3), and it had decreased to 0.042 ± 0.002 μm by 2 h. Reference: Mol Cancer Ther. 2003 Aug;2(8):721-8. http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=12939461|
|Solvent||Max Conc. mg/mL||Max Conc. mM|
The following data is based on the product molecular weight 318.34 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.
|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|
|In vitro protocol:||1. Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8. PMID: 12939461. 2. Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8. PMID: 12939461.|
|In vivo protocol:||1. Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8. PMID: 12939461. 2. Plumb JA, Finn PW, Williams RJ, Bandara MJ, Romero MR, Watkins CJ, La Thangue NB, Brown R. Pharmacodynamic response and inhibition of growth of human tumor xenografts by the novel histone deacetylase inhibitor PXD101. Mol Cancer Ther. 2003 Aug;2(8):721-8. PMID: 12939461.|
1: Odenike O, Halpern A, Godley LA, Madzo J, Karrison T, Green M, Fulton N, Mattison RJ, Yee KW, Bennett M, Koval G, Malnassy G, Larson RA, Ratain MJ, Stock W. A phase I and pharmacodynamic study of the histone deacetylase inhibitor belinostat plus azacitidine in advanced myeloid neoplasia. Invest New Drugs. 2014 Dec 9. [Epub ahead of print] PubMed PMID: 25483416.
2: Kim MJ, Lee JS, Park SE, Yi HJ, Jeong IG, Kang JS, Yun J, Lee JY, Ro S, Lee JS, Choi EK, Hwang JJ, Kim CS. Combination treatment of renal cell carcinoma with belinostat and 5-fluorouracil: A role for oxidative stress-induced DNA damage and HSP90-regulated thymidine synthase. J Urol. 2014 Nov 26. pii: S0022-5347(14)05012-5. doi: 10.1016/j.juro.2014.11.091. [Epub ahead of print] PubMed PMID: 25433307.
3: Foss F, Advani R, Duvic M, Hymes KB, Intragumtornchai T, Lekhakula A, Shpilberg O, Lerner A, Belt RJ, Jacobsen ED, Laurent G, Ben-Yehuda D, Beylot-Barry M, Hillen U, Knoblauch P, Bhat G, Chawla S, Allen LF, Pohlman B. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2014 Nov 17. doi: 10.1111/bjh.13222. [Epub ahead of print] PubMed PMID: 25404094.
4: Bodiford A, Bodge M, Talbott MS, Reddy NM. Profile of belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. Onco Targets Ther. 2014 Oct 24;7:1971-7. doi: 10.2147/OTT.S59269. eCollection 2014. Review. PubMed PMID: 25368524; PubMed Central PMCID: PMC4216035.
5: Thomas A, Rajan A, Szabo E, Tomita Y, Carter CA, Scepura B, Lopez-Chavez A, Lee MJ, Redon CE, Frosch A, Peer CJ, Chen Y, Piekarz R, Steinberg SM, Trepel JB, Figg WD, Schrump DS, Giaccone G. A phase I/II trial of belinostat in combination with cisplatin, doxorubicin, and cyclophosphamide in thymic epithelial tumors: a clinical and translational study. Clin Cancer Res. 2014 Nov 1;20(21):5392-402. doi: 10.1158/1078-0432.CCR-14-0968. Epub 2014 Sep 4. PubMed PMID: 25189481; PubMed Central PMCID: PMC4216756.
6: Poole RM. Belinostat: first global approval. Drugs. 2014 Sep;74(13):1543-54. doi: 10.1007/s40265-014-0275-8. PubMed PMID: 25134672.
7: Thompson CA. Belinostat approved for use in treating rare lymphoma. Am J Health Syst Pharm. 2014 Aug 15;71(16):1328. doi: 10.2146/news140056. PubMed PMID: 25074945.
8: McDermott J, Jimeno A. Belinostat for the treatment of peripheral T-cell lymphomas. Drugs Today (Barc). 2014 May;50(5):337-45. doi: 10.1358/dot.2014.50.5.2138703. Review. PubMed PMID: 24918834.
9: Savickiene J, Treigyte G, Valiuliene G, Stirblyte I, Navakauskiene R. Epigenetic and molecular mechanisms underlying the antileukemic activity of the histone deacetylase inhibitor belinostat in human acute promyelocytic leukemia cells. Anticancer Drugs. 2014 Sep;25(8):938-49. doi: 10.1097/CAD.0000000000000122. PubMed PMID: 24800886.
10: Kirschbaum MH, Foon KA, Frankel P, Ruel C, Pulone B, Tuscano JM, Newman EM. A phase 2 study of belinostat (PXD101) in patients with relapsed or refractory acute myeloid leukemia or patients over the age of 60 with newly diagnosed acute myeloid leukemia: a California Cancer Consortium Study. Leuk Lymphoma. 2014 Oct;55(10):2301-4. doi: 10.3109/10428194.2013.877134. Epub 2014 Feb 24. PubMed PMID: 24369094; PubMed Central PMCID: PMC4143479.
Belinostat (PXD101, trade name Beleodaq) is a drug under development by TopoTarget for the treatment of hematological malignancies and solid tumors. It is a histone deacetylase inhibitor. In 2007 preliminary results were released from the Phase II clinical trial of intravenous belinostat in combination with carboplatin and paclitaxel for relapsed ovarian cancer. Final results in late 2009 of a phase II trial for T-cell lymphoma were encouraging. Belinostat has been granted orphan drug and fast track designation by the FDA, and was approved in the US for the use against peripheral T-cell lymphoma. (http://en.wikipedia.org/wiki/Belinostat).