MedKoo Cat#: 462355 | Name: Nanatinostat
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Nanatinostat, also known as Tractinostat, CHR-3996 and VRx-3996, is an orally bioavailable, second-generation hydroxamic acid-based inhibitor of histone deacetylase (HDAC) with potential antineoplastic activity. HDAC inhibitor CHR-3996 inhibits HDAC, resulting in an accumulation of highly acetylated histones, the induction of chromatin remodeling, and the selective transcription of tumor suppressor genes; these events may result in the inhibition of tumor cell division and the induction of tumor cell apoptosis. This agent may upregulate HSP70 and downregulate anti-apoptotic Bcl-2 proteins more substantially than some first-generation HDAC inhibitors. HDACs, upregulated in many tumor cell types, are a family of metalloenzymes responsible for the deacetylation of chromatin histone proteins.

Chemical Structure

Nanatinostat
Nanatinostat
CAS#1256448-47-1 (free base)

Theoretical Analysis

MedKoo Cat#: 462355

Name: Nanatinostat

CAS#: 1256448-47-1 (free base)

Chemical Formula: C20H19FN6O2

Exact Mass: 394.1554

Molecular Weight: 394.41

Elemental Analysis: C, 60.91; H, 4.86; F, 4.82; N, 21.31; O, 8.11

Price and Availability

Size Price Availability Quantity
5mg USD 650.00 2 Weeks
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Related CAS #
914937-68-1 (racemic) 1256448-47-1 (free base) 1256448-48-2 (TFA) 2648504-17-8 (hydrate) 1235859-13-8 (deleted)
Synonym
CHR3996; CHR-3996; CHR 3996; VRx-3996; VRx3996; VRx 3996; Nanatinostat; Tractinostat;
IUPAC/Chemical Name
2-((1R,5S,6s)-6-(((6-fluoroquinolin-2-yl)methyl)amino)-3-azabicyclo[3.1.0]hexan-3-yl)-N-hydroxypyrimidine-4-carboxamide
InChi Key
GTAUPYWUPNCTCZ-HWWDLCQESA-N
InChi Code
InChI=1S/C20H19FN6O2/c21-12-2-4-16-11(7-12)1-3-13(24-16)8-23-18-14-9-27(10-15(14)18)20-22-6-5-17(25-20)19(28)26-29/h1-7,14-15,18,23,29H,8-10H2,(H,26,28)/t14-,15+,18+
SMILES Code
FC1=CC=C2N=C(CN[C@H]3[C@]4([H])CN(C5=NC=CC(C(NO)=O)=N5)C[C@]34[H])C=CC2=C1
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO
Shelf Life
>3 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Product Data
Biological target:
Nanatinostat (CHR-3996) is a potent, class I selective and orally active histone deacetylase (HDAC) inhibitor with an IC50 of 8 nM.
In vitro activity:
CHR-3996 was shown to inhibit the proliferation of a panel of myeloma cells using the WST-1 assay based on metabolic activity (Figure 1A). The LC50 values for the various cell lines treated with CHR-3996 ranged from 30.3-97.6nM. In comparison to two commercially available HDAC inhibitors, SAHA and Sodium Valproate, CHR-3996 was shown to be effective at much lower concentrations and was approximately 10-fold more potent than SAHA and 10-thousand fold more potent than Sodium Valproate (Supplementary Table 1). Reference: Oncotarget. 2015 Jul 10;6(19):17314-27. https://pubmed.ncbi.nlm.nih.gov/26015393/
In vivo activity:
Administration of CHR-3996 in a NOD/SCID IL2R gammanull xenograft model effectively inhibited tumour growth at doses that were well tolerated (Figure 5A). Reference: Oncotarget. 2015 Jul 10;6(19):17314-27. https://pubmed.ncbi.nlm.nih.gov/26015393/
Solvent mg/mL mM
Solubility
DMSO 33.3 84.51
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 394.41 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
Smith EM, Zhang L, Walker BA, Davenport EL, Aronson LI, Krige D, Hooftman L, Drummond AH, Morgan GJ, Davies FE. 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. doi: 10.18632/oncotarget.1168. PMID: 26015393; PMCID: PMC4627310.
In vitro protocol:
Smith EM, Zhang L, Walker BA, Davenport EL, Aronson LI, Krige D, Hooftman L, Drummond AH, Morgan GJ, Davies FE. 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. doi: 10.18632/oncotarget.1168. PMID: 26015393; PMCID: PMC4627310.
In vivo protocol:
Smith EM, Zhang L, Walker BA, Davenport EL, Aronson LI, Krige D, Hooftman L, Drummond AH, Morgan GJ, Davies FE. 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. doi: 10.18632/oncotarget.1168. PMID: 26015393; PMCID: PMC4627310.
1: Singh AN, Sharma N. Epigenetic Modulators as Potential Multi-targeted Drugs Against Hedgehog Pathway for Treatment of Cancer. Protein J. 2019 Oct;38(5):537-550. doi: 10.1007/s10930-019-09832-9. PMID: 30993446. 2: Garrido-Laguna I, Tometich D, Hu N, Ying J, Geiersbach K, Whisenant J, Wang K, Ross JS, Sharma S. N of 1 case reports of exceptional responders accrued from pancreatic cancer patients enrolled in first-in-man studies from 2002 through 2012. Oncoscience. 2015 Mar 14;2(3):285-93. doi: 10.18632/oncoscience.141. PMID: 25897431; PMCID: PMC4394134. 3: Smith EM, Zhang L, Walker BA, Davenport EL, Aronson LI, Krige D, Hooftman L, Drummond AH, Morgan GJ, Davies FE. 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. doi: 10.18632/oncotarget.1168. PMID: 26015393; PMCID: PMC4627310. 4: Banerji U, van Doorn L, Papadatos-Pastos D, Kristeleit R, Debnam P, Tall M, Stewart A, Raynaud F, Garrett MD, Toal M, Hooftman L, De Bono JS, Verweij J, Eskens FA. 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. doi: 10.1158/1078-0432.CCR-11-3165. PMID: 22553374. 5: Moffat D, Patel S, Day F, Belfield A, Donald A, Rowlands M, Wibawa J, Brotherton D, Stimson L, Clark V, Owen J, Bawden L, Box G, Bone E, Mortenson P, Hardcastle A, van Meurs S, Eccles S, Raynaud F, Aherne W. 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. doi: 10.1021/jm101177s. Epub 2010 Nov 16. PMID: 21080647. 6: Al-Shamahi A, Murch L, Kirkham K. American Society of Clinical Oncology--46th annual meeting. IDrugs. 2010 Aug;13(8):506-9. PMID: 20721815.