From Wikipedia, the free encyclopedia
Chemical compound
Quisinostat
Other names JNJ-26481585
ATC code
Bioavailability oral
[1]
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 )
Formula C 21 H 26 N 6 O 2
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]
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
^
"NCI Drug Dictionary" . National Cancer Institute . 2 February 2011.
^
"Quisinostat" (PDF) .
American Medical Association .
^ 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 .
^ 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 .
^
"Quisinostat" . NCI Drug Dictionary .
National Cancer Institute .
^ 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 .
^
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 .
^ 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 .