Belinostat
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MedKoo CAT#: 200460

CAS#: 866323-14-0

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.

Chemical Structure

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Belinostat
CAS# 866323-14-0
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 200460
Name: Belinostat
CAS#: 866323-14-0
Chemical Formula: C15H14N2O4S
Exact Mass: 318.07
Molecular Weight: 318.340
Elemental Analysis: C, 56.59; H, 4.43; N, 8.80; O, 20.10; S, 10.07.

Price and Availability

Size Price Availability Quantity
50mg USD 150 Ready to ship
100mg USD 250 Ready to ship
200mg USD 450 Ready to ship
500mg USD 950 Ready to ship
1g USD 1650 Ready to ship
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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

More Info: 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).  

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

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 64.0 201.40

Preparing Stock Solutions

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.

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:
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.

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1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012–. Belinostat. 2020 Sep 25. PMID: 31644024.


2: Shen Y, Yang R, Zhao J, Chen M, Chen S, Ji B, Chen H, Liu D, Li L, Du G. The histone deacetylase inhibitor belinostat ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting TLR2/MyD88 and HDAC3/ NF-κB p65-mediated neuroinflammation. Pharmacol Res. 2022 Feb;176:105969. doi: 10.1016/j.phrs.2021.105969. Epub 2021 Nov 7. PMID: 34758400.


3: Campbell P, Thomas CM. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. J Oncol Pharm Pract. 2017 Mar;23(2):143-147. doi: 10.1177/1078155216634178. Epub 2016 Jun 23. PMID: 26921086.


4: Belinostat (Beleodaq) for peripheral T-Cell lymphoma. Med Lett Drugs Ther. 2015 Apr 27;57(1467):e66-7. PMID: 25988963.


5: Hood K, Shah A. Belinostat for Relapsed or Refractory Peripheral T-Cell Lymphoma. J Adv Pract Oncol. 2016 Mar;7(2):209-218. doi: 10.6004/jadpro.2016.7.2.6. Epub 2016 Mar 1. PMID: 28090369; PMCID: PMC5226312.


6: Goey AK, Figg WD. UGT genotyping in belinostat dosing. Pharmacol Res. 2016 Mar;105:22-7. doi: 10.1016/j.phrs.2016.01.002. Epub 2016 Jan 7. PMID: 26773202; PMCID: PMC4775324.


7: 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. PMID: 24918834.


8: Molife LR, de Bono JS. Belinostat: clinical applications in solid tumors and lymphoma. Expert Opin Investig Drugs. 2011 Dec;20(12):1723-32. doi: 10.1517/13543784.2011.629604. Epub 2011 Nov 3. PMID: 22046971.


9: Sawas A, Radeski D, O'Connor OA. Belinostat in patients with refractory or relapsed peripheral T-cell lymphoma: a perspective review. Ther Adv Hematol. 2015 Aug;6(4):202-8. doi: 10.1177/2040620715592567. PMID: 26288714; PMCID: PMC4530372.


10: Rashidi A, Cashen AF. Belinostat for the treatment of relapsed or refractory peripheral T-cell lymphoma. Future Oncol. 2015;11(11):1659-64. doi: 10.2217/fon.15.62. PMID: 26043217.


11: O'Connor OA, Horwitz S, Masszi T, Van Hoof A, Brown P, Doorduijn J, Hess G, Jurczak W, Knoblauch P, Chawla S, Bhat G, Choi MR, Walewski J, Savage K, Foss F, Allen LF, Shustov A. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015 Aug 10;33(23):2492-9. doi: 10.1200/JCO.2014.59.2782. Epub 2015 Jun 22. PMID: 26101246; PMCID: PMC5087312.


12: Quah S, Subramanian G, Sampath P. Repurposing Belinostat for Alleviation of Atopic Dermatitis. Dermatol Ther (Heidelb). 2021 Jun;11(3):655-660. doi: 10.1007/s13555-021-00527-7. Epub 2021 Apr 14. PMID: 33852133; PMCID: PMC8163942.


13: Jia HJ, Ge Y, Xia J, Shi YL, Wang XB. Belinostat (PXD101) resists UVB irradiation-induced cellular senescence and skin photoaging. Biochem Biophys Res Commun. 2022 Oct 30;627:122-129. doi: 10.1016/j.bbrc.2022.08.038. Epub 2022 Aug 17. PMID: 36030653.


14: Eckschlager T, Plch J, Stiborova M, Hrabeta J. Histone Deacetylase Inhibitors as Anticancer Drugs. Int J Mol Sci. 2017 Jul 1;18(7):1414. doi: 10.3390/ijms18071414. PMID: 28671573; PMCID: PMC5535906.


15: 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. PMID: 25368524; PMCID: PMC4216035.


16: Poh C, Arora M, Ghuman S, Tuscano J. Belinostat in Relapsed/Refractory T-Cell Large Granular Lymphocyte Leukemia. Acta Haematol. 2021;144(1):95-99. doi: 10.1159/000506918. Epub 2020 Apr 29. PMID: 32348994.


17: Pulya S, Amin SA, Adhikari N, Biswas S, Jha T, Ghosh B. HDAC6 as privileged target in drug discovery: A perspective. Pharmacol Res. 2021 Jan;163:105274. doi: 10.1016/j.phrs.2020.105274. Epub 2020 Nov 7. PMID: 33171304.


18: Kenny RG, Ude Z, Docherty JR, Marmion CJ. Vorinostat and Belinostat, hydroxamate-based anti-cancer agents, are nitric oxide donors. J Inorg Biochem. 2020 May;206:110981. doi: 10.1016/j.jinorgbio.2019.110981. Epub 2019 Dec 27. PMID: 32088592.


19: Lu P, Gu Y, Li L, Wang F, Yang X, Yang Y. Belinostat suppresses cell proliferation by inactivating Wnt/β-catenin pathway and promotes apoptosis through regulating PKC pathway in breast cancer. Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3955-3960. doi: 10.1080/21691401.2019.1671855. Retraction in: Artif Cells Nanomed Biotechnol. 2021 Dec;49(1):287. PMID: 31571495.


20: Poole RM. Belinostat: first global approval. Drugs. 2014 Sep;74(13):1543-54. doi: 10.1007/s40265-014-0275-8. PMID: 25134672.