Physicochemical Properties
| Molecular Formula | C29H25FN4O4 |
| Molecular Weight | 512.53 |
| Exact Mass | 512.185 |
| CAS # | 2411379-14-9 |
| PubChem CID | 163322268 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 3.9 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 38 |
| Complexity | 911 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CN1C2C3=C(CCN2C(=O)C4=C1C=CC(=C4)F)C5=C(N3)C=CC(=C5)OCC6=CC=C(C=C6)/C=C/C(=O)NO |
| InChi Key | OYPZLONUGJGMDS-IZZDOVSWSA-N |
| InChi Code | InChI=1S/C29H25FN4O4/c1-33-25-10-7-19(30)14-23(25)29(36)34-13-12-21-22-15-20(8-9-24(22)31-27(21)28(33)34)38-16-18-4-2-17(3-5-18)6-11-26(35)32-37/h2-11,14-15,28,31,37H,12-13,16H2,1H3,(H,32,35)/b11-6+ |
| Chemical Name | (E)-3-[4-[(17-fluoro-21-methyl-14-oxo-3,13,21-triazapentacyclo[11.8.0.02,10.04,9.015,20]henicosa-2(10),4(9),5,7,15(20),16,18-heptaen-7-yl)oxymethyl]phenyl]-N-hydroxyprop-2-enamide |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | HDAC/Top-IN-1 (compound 16j) (0-2 μM; 48 hours) demonstrated noteworthy inhibitory action on the evaluated cell lines [1]. In HEL cells, HDAC/Top-IN-1 (20 and 100 nM; 24 hours) dramatically raises acetyl-H3 and acetyl-H4 levels [1]. HDAC/Top-IN-1 efficiently promotes apoptosis in HEL cells in a dose-dependent manner (0.1 and 0.5 μM; 48 hours) [1]. In 48 hours, HDAC/Top-IN-1 (0.02-0.5 μM) stops HEL cells in S phase [1]. |
| ln Vivo | HDAC/Top-IN-1 has good metabolic properties, with a 173.32 mL/min/mg clearance rate and a half-life (T1/2) of 31.49 minutes[1]. HDAC/Top-IN-1 has strong oral antitumor activity when taken orally for 14 days at doses of 5 and 10 mg/kg [1]. |
| Cell Assay |
Cell proliferation experiment Cell Types: MCF-7, A549, HCT116, HepG-2, K562 and HEL[1] Tested Concentrations: 0-2 μM Incubation Duration: 48 hrs (hours) Experimental Results: demonstrated significant inhibitory activity on the tested cell lines, IC50s are 0.68, 0.21, 0.26, 0.35 and 0.029 μM in MCF-7, A549, HCT116, HepG-2, K562 and HEL respectively. Western Blot Analysis Cell Types: HEL[1] Tested Concentrations: 20 and 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Significant increase in acetyl-H3 and acetyl-H4 levels. Apoptosis analysis Cell Types: HEL[1] Tested Concentrations: 0.1 and 0.5 μM Incubation Duration: 48 hrs (hours) Experimental Results: At concentrations of 0.1 and 0.5 μM, the cell apoptosis rates were 56.02% and 76.45%, respectively Cell cycle analysis Cell Types: HEL [1 ] Tested Concentrations: 0.02, 0.1 and 0.5 μM Incubation Duration: 48 hrs (hours) Experimental Results: The proportion of S phase changed Dramatically at 0.02, 0.1 and 0.5 μM, which were 9.8%, 15.4% and 25.8% respectively. |
| Animal Protocol |
Animal/Disease Models: Female BALB/C nude mice (5-6 weeks, 18-20 g; injected with human K562 cells) [1] Doses: 5 and 10 mg/kg Route of Administration: Oral; one time/day for 14 days Experimental Results: 5 mg/kg demonstrated effective anti-tumor activity when taken orally, with a TGI value of 41.4% and a T/C value of 54.3%, and achieved better tumor growth inhibition with a TGI of 68.5% and a T/C value of 25.5%. |
| References | [1]. Wu S, Huang Y, Wang T, et al. Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy. J Med Chem. 2022;65(6):4818-4831. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9511 mL | 9.7555 mL | 19.5111 mL | |
| 5 mM | 0.3902 mL | 1.9511 mL | 3.9022 mL | |
| 10 mM | 0.1951 mL | 0.9756 mL | 1.9511 mL |