Quisinostat

Last updated
Quisinostat
Quisinostat.svg
Clinical data
Other namesJNJ-26481585
ATC code
  • None
Pharmacokinetic data
Bioavailability oral [1]
Identifiers
  • N-Hydroxy-2-[4-({[(1-methyl-1H-indol-3-yl)methyl]amino}methyl)-1-piperidinyl]-5-pyrimidinecarboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H26N6O2
Molar mass 394.479 g·mol−1
3D model (JSmol)
  • O=C(NO)c1cnc(nc1)N2CCC(CC2)CNCc4c3ccccc3n(c4)C
  • InChI=1S/C21H26N6O2/c1-26-14-17(18-4-2-3-5-19(18)26)11-22-10-15-6-8-27(9-7-15)21-23-12-16(13-24-21)20(28)25-29/h2-5,12-15,22,29H,6-11H2,1H3,(H,25,28)
  • Key:PAWIYAYFNXQGAP-UHFFFAOYSA-N

Quisinostat (USAN; [2] development code JNJ-26481585) is an experimental drug candidate for the treatment of cancer. It is a "second generation" histone deacetylase inhibitor with antineoplastic activity. [3] [4] [5] It is highly potent against class I and II HDACs. [6]

Contents

History

It was developed by Janssen Pharmaceuticals and licensed to NewVac LLC. [7]

Preclinical studies show that quisinostat amplifies HDAC-repressed expression of E-cadherin, leading to a reversal of epithelial to mesenchymal transition in tumor cells. [7]

Clinical trials

Results of a phase I trials in patients with multiple myeloma in combination with bortezomib and dexamethasone were published in 2016. [8]

Related Research Articles

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References

  1. "NCI Drug Dictionary". National Cancer Institute. 2 February 2011.
  2. "Quisinostat" (PDF). American Medical Association.
  3. Tong WG, Wei Y, Stevenson W, Kuang SQ, Fang Z, Zhang M, et al. (February 2010). "Preclinical antileukemia activity of JNJ-26481585, a potent second-generation histone deacetylase inhibitor". Leukemia Research. 34 (2): 221–8. doi:10.1016/j.leukres.2009.07.024. PMID   19682743.
  4. Stühmer T, Arts J, Chatterjee M, Borawski J, Wolff A, King P, et al. (May 2010). "Preclinical anti-myeloma activity of the novel HDAC-inhibitor JNJ-26481585". British Journal of Haematology. 149 (4): 529–36. doi: 10.1111/j.1365-2141.2010.08126.x . PMID   20331455. S2CID   42077659.
  5. "Quisinostat". NCI Drug Dictionary. National Cancer Institute.
  6. Carol H, Gorlick R, Kolb EA, Morton CL, Manesh DM, Keir ST, et al. (February 2014). "Initial testing (stage 1) of the histone deacetylase inhibitor, quisinostat (JNJ-26481585), by the Pediatric Preclinical Testing Program". Pediatric Blood & Cancer. 61 (2): 245–52. doi:10.1002/pbc.24724. PMC   4225045 . PMID   24038993.
  7. 1 2 LLC, NewVac. "NewVac Reports Primary Endpoint Met in Phase II Clinical Trial of Quisinostat in Combination with Paclitaxel and Carboplatin in Platinum-Resistant Ovarian Cancer". www.prnewswire.com.
  8. Moreau P, Facon T, Touzeau C, Benboubker L, Delain M, Badamo-Dotzis J, et al. (July 2016). "Quisinostat, bortezomib, and dexamethasone combination therapy for relapsed multiple myeloma". Leukemia & Lymphoma. 57 (7): 1546–59. doi:10.3109/10428194.2015.1117611. PMID   26758913. S2CID   42026457.