Synonym
AZ505 2TFA salt; AZ 505 2TFA salt; AZ-505 2TFA salt
IUPAC/Chemical Name
N-cyclohexyl-3-((3,4-dichlorophenethyl)amino)-N-(2-((2-(5-hydroxy-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-8-yl)ethyl)amino)ethyl)propanamide bis(2,2,2-trifluoroacetate)
InChi Key
LTZSXVZCRINTGV-UHFFFAOYSA-N
InChi Code
InChI=1S/C29H38Cl2N4O4.2C2HF3O2/c30-23-8-6-20(18-24(23)31)10-13-32-15-12-27(38)35(22-4-2-1-3-5-22)17-16-33-14-11-21-7-9-25(36)28-29(21)39-19-26(37)34-28;2*3-2(4,5)1(6)7/h6-9,18,22,32-33,36H,1-5,10-17,19H2,(H,34,37);2*(H,6,7)
SMILES Code
O=C(N(C1CCCCC1)CCNCCC2=C(C(N3)=C(O)C=C2)OCC3=O)CCNCCC4=CC=C(Cl)C(Cl)=C4.O=C(O)C(F)(F)F.O=C(O)C(F)(F)F
Appearance
white 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, not in water
Shelf Life
>2 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
Biological target:
AZ505 ditrifluoroacetate is a potent and selective SMYD2 inhibitor with IC50 of 0.12 μM.
In vitro activity:
Knockdown of Smyd2 inhibited Pkd1 mutant renal epithelial cell growth as examined by MTT assay (Supplemental Figure 2, A and B) and decreased S-phase entry as determined by flow cytometry (FACS) analysis (Supplemental Figure 2C). Treatment with AZ505 further decreased S-phase entry in Smyd2-knockdown Pkd1 mutant renal epithelial cells compared with that in DMSO-treated Smyd2-knockdown cells (Supplemental Figure 2C), which might be caused by the inhibition of AZ505 on the remaining SMYD2 in the Smyd2-knockdown Pkd1 mutant renal epithelial cells. These results support the specificity of AZ505 for the inhibition of SMYD2.
Reference: Cell Death Dis. 2018 Feb 27;9(3):326. https://pubmed.ncbi.nlm.nih.gov/28604386/
In vivo activity:
This study further found that the tumor growth in MDA-MB231 implanted female nude mice was significantly retarded by daily intraperitoneal injections of AZ505 at a dose of 40 mg/kg body weight (Figs. 4a–c). AZ505 treatment also decreased tumor cell proliferation and induced tumor cell apoptosis as seen by Ki67 staining (Fig. 4d) and TUNEL analysis (Fig. 4e). The effect of AZ505 on inhibition of TNBC growth was also confirmed in nude mice with MDA-MB468 xenografts (Figs. 4f–j). Our results suggest that SMYD2 may serve as a potent therapeutic target in TNBC treatment justifying further investigation into the mechanisms of SMYD2 in TNBC development.
Reference: Cell Death Dis. 2018 Feb 27;9(3):326. https://pubmed.ncbi.nlm.nih.gov/29487338/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
125.0 |
216.43 |
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
577.54
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.
| 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:
1. Parmar N, Chandrakar P, Kar S. Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization. J Immunol. 2020 May 15;204(10):2762-2778. doi: 10.4049/jimmunol.1900251. Epub 2020 Apr 10. PMID: 32277055.
2. Li LX, Fan LX, Zhou JX, Grantham JJ, Calvet JP, Sage J, Li X. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 2017 Jun 30;127(7):2751-2764. doi: 10.1172/JCI90921. Epub 2017 Jun 12. PMID: 28604386; PMCID: PMC5490754.
3. Li LX, Zhou JX, Calvet JP, Godwin AK, Jensen RA, Li X. Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression. Cell Death Dis. 2018 Feb 27;9(3):326. doi: 10.1038/s41419-018-0347-x. PMID: 29487338; PMCID: PMC5832424.
In vitro protocol:
1. Parmar N, Chandrakar P, Kar S. Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization. J Immunol. 2020 May 15;204(10):2762-2778. doi: 10.4049/jimmunol.1900251. Epub 2020 Apr 10. PMID: 32277055.
2. Li LX, Fan LX, Zhou JX, Grantham JJ, Calvet JP, Sage J, Li X. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 2017 Jun 30;127(7):2751-2764. doi: 10.1172/JCI90921. Epub 2017 Jun 12. PMID: 28604386; PMCID: PMC5490754.
In vivo protocol:
1. Parmar N, Chandrakar P, Kar S. Leishmania donovani Subverts Host Immune Response by Epigenetic Reprogramming of Macrophage M(Lipopolysaccharides + IFN-γ)/M(IL-10) Polarization. J Immunol. 2020 May 15;204(10):2762-2778. doi: 10.4049/jimmunol.1900251. Epub 2020 Apr 10. PMID: 32277055.
2. Li LX, Zhou JX, Calvet JP, Godwin AK, Jensen RA, Li X. Lysine methyltransferase SMYD2 promotes triple negative breast cancer progression. Cell Death Dis. 2018 Feb 27;9(3):326. doi: 10.1038/s41419-018-0347-x. PMID: 29487338; PMCID: PMC5832424.
1: Li LX, Fan LX, Zhou JX, Grantham JJ, Calvet JP, Sage J, Li X. Lysine methyltransferase SMYD2 promotes cyst growth in autosomal dominant polycystic kidney disease. J Clin Invest. 2017 Jun 30;127(7):2751-2764. doi: 10.1172/JCI90921. Epub 2017 Jun 12. PubMed PMID: 28604386; PubMed Central PMCID: PMC5490754.
2: de Grass D, Manie S, Amosun SL. Effectiveness of a home-based pulmonary rehabilitation programme in pulmonary function and health related quality of life for patients with pulmonary tuberculosis: a pilot study. Afr Health Sci. 2014 Dec;14(4):866-72. doi: 10.4314/ahs.v14i4.14. PubMed PMID: 25834495; PubMed Central PMCID: PMC4370065.
3: Ferguson AD, Larsen NA, Howard T, Pollard H, Green I, Grande C, Cheung T, Garcia-Arenas R, Cowen S, Wu J, Godin R, Chen H, Keen N. Structural basis of substrate methylation and inhibition of SMYD2. Structure. 2011 Sep 7;19(9):1262-73. doi: 10.1016/j.str.2011.06.011. Epub 2011 Jul 21. PubMed PMID: 21782458.
