Quisinostat

Quisinostat
Clinical data
Other namesJNJ-26481585
ATC code
  • None
Pharmacokinetic data
Bioavailabilityoral[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
ChEBI
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC21H26N6O2
Molar mass394.479 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]

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]

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. ^ a b 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 (Press release).
  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.

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