Nanatinostat (CHR-3996) is a potent, class I selective and orally active HDAC inhibitor with IC₅₀s of 3 nM, 4 nM, and 7 nM for HDAC1, HDAC2, and HDAC3, respectively. Nanatinostat has low activity against HDAC5 (IC₅₀ of 200 nM) and HDAC6 (IC₅₀ of 2100 nM). Nanatinostat induces apoptosis in myeloma cells. Nanatinostat has potent anticancer effects, such as myeloma, advanced solid tumours and colorectal cancer^[1][2][3].

Nanatinostat (CHR-3996) (0.0001-1 μM; 48 hours) inhibits the proliferation of myeloma cell lines, with LC₅₀ values ranging from 30.3-97.6 nM in different cell lines^[2].
Nanatinostat (250-100 nM; 8-48 hours) induces apoptosis and increases the level of acetylated H3K9 in H929 and RPMI-8226 myeloma cell lines^[2].
Nanatinostat (0-200 nM; 24 hours) reduces the levels of IL-6 and VEGF secreted by bone marrow stromal cells in the co-culture system of bone marrow stromal cells and myeloma cells^[2].
Nanatinostat (250 nM and 100 nM; 48 hours) arrests the cell cycle at the G0/G1 phase in H929 and RPMI-8226 myeloma cell lines^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Nanatinostat (50 mg/kg; orally administered; once daily; for 14 days) can almost completely inhibit tumor growth in the female CrTac:NCr-Fox1ν mouse HCT116 tumor xenograft model^[1].
Nanatinostat (25-50 mg/kg; orally administered; once daily; for 19 days) can significantly reduce tumor volume in a dose-dependent manner in the female BALB/c nude mouse LoVo human colon xenograft model^[1].
Nanatinostat (30 mg/kg; orally administered; once daily; for 28 days) can effectively inhibit tumor growth in the NOD/SCID IL2R gamma^null mouse myeloma model^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

394.40

C₂₀H₁₉FN₆O₂

1256448-47-1

Solid

White to off-white

FC(C=C1)=CC(C=C2)=C1N=C2CN[C@H]3[C@@]4(05)[C@]3(05)CN(C5=NC=C(C(NO)=O)C=N5)C4

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen

*In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Moffat D, et al. Discovery of 2-(6-{[(6-fluoroquinolin-2-yl)methyl]amino}bicyclo[3.1.0]hex-3-yl)-N-hydroxypyrimidine-5-carboxamide (CHR-3996), a class I selective orally active histone deacetylase inhibitor. J Med Chem. 2010 Dec 23;53(24):8663-78.  [Content Brief]

  [2]. Smith EM, et al. The combination of HDAC and aminopeptidase inhibitors is highly synergistic in myeloma and leads to disruption of the NFκB signalling pathway. Oncotarget. 2015 Jul 10;6(19):17314-27.  [Content Brief]

  [3]. Banerji U, et al. A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors. Clin Cancer Res. 2012 May 1;18(9):2687-94.  [Content Brief]