Quisinostat

Quisinostat
Clinical data
Other names	JNJ-26481585
ATC code	None;
Pharmacokinetic data
Bioavailability	oral
Identifiers
	IUPAC name N-Hydroxy-2-[4-({[(1-methyl-1H-indol-3-yl)methyl]amino}methyl)-1-piperidinyl]-5-pyrimidinecarboxamide;
CAS Number	875320-29-9 ;
PubChem CID	11538455;
ChemSpider	9713236;
UNII	9BJ85K1J8S;
KEGG	D10321;
ChEBI	CHEBI:94771;
CompTox Dashboard (EPA)	DTXSID90236376 ;
Chemical and physical data
Formula	C21H26N6O2
Molar mass	394.479 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]

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 (Press release).
^ 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.

[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.

[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 (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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