Quisinostat

Quisinostat
Clinical data
Other names	JNJ-26481585
ATC code	None;
Pharmacokinetic data
Bioavailability	oral[1]
Identifiers
	IUPAC name N-Hydroxy-2-[4-({[(1-methyl-1H-indol-3-yl)methyl]amino}methyl)-1-piperidinyl]-5-pyrimidinecarboxamide;
PubChem CID	11538455;
ChemSpider	9713236;
KEGG	D10321;
CompTox Dashboard (EPA)	DTXSID90236376 ;
Chemical and physical data
Formula	C21H26N6O2
Molar mass	394.470 g/mol g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(NO)c1cnc(nc1)N2CCC(CC2)CNCc4c3ccccc3n(c4)C;
	InChI 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]

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] 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, Wei-Gang; Wei, Yue; Stevenson, William; Kuang, Shao-Qing; Fang, Zhihong; Zhang, Ming; Arts, Janine; Garcia-Manero, Guillermo (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, Thorsten; Arts, Janine; Chatterjee, Manik; Borawski, Johanna; Wolff, André; King, Peter; Einsele, Hermann; Leo, Eugen; Bargou, Ralf C. (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.
"Quisinostat". NCI Drug Dictionary. National Cancer Institute.
Carol, Hernan; Gorlick, Richard; Kolb, E. Anders; Morton, Christopher L.; Manesh, Donya Moradi; Keir, Stephen T.; Reynolds, C. Patrick; Kang, Min H.; Maris, John M.; Wozniak, Amy; Hickson, Ian; Lyalin, Dmitry; Kurmasheva, Raushan T.; Houghton, Peter J.; Smith, Malcolm A.; Lock, Richard (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.
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, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier (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.

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[1] "NCI Drug Dictionary". National Cancer Institute. 2 February 2011.

[2] "Quisinostat" (PDF). American Medical Association.

[3] Tong, Wei-Gang; Wei, Yue; Stevenson, William; Kuang, Shao-Qing; Fang, Zhihong; Zhang, Ming; Arts, Janine; Garcia-Manero, Guillermo (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, Thorsten; Arts, Janine; Chatterjee, Manik; Borawski, Johanna; Wolff, André; King, Peter; Einsele, Hermann; Leo, Eugen; Bargou, Ralf C. (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.

[5] "Quisinostat". NCI Drug Dictionary. National Cancer Institute.

[6] Carol, Hernan; Gorlick, Richard; Kolb, E. Anders; Morton, Christopher L.; Manesh, Donya Moradi; Keir, Stephen T.; Reynolds, C. Patrick; Kang, Min H.; Maris, John M.; Wozniak, Amy; Hickson, Ian; Lyalin, Dmitry; Kurmasheva, Raushan T.; Houghton, Peter J.; Smith, Malcolm A.; Lock, Richard (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.

[auto-7] 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, Philippe; Facon, Thierry; Touzeau, Cyrille; Benboubker, Lotfi; Delain, Martine; Badamo-Dotzis, Julie; Phelps, Charles; Doty, Christopher; Smit, Hans; Fourneau, Nele; Forslund, Ann; Hellemans, Peter; Leleu, Xavier (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.