Physicochemical Properties
| Molecular Formula | C21H19N3O4 |
| Molecular Weight | 377.393265008926 |
| Exact Mass | 377.14 |
| Elemental Analysis | C, 66.83; H, 5.07; N, 11.13; O, 16.96 |
| CAS # | 2716217-79-5 |
| PubChem CID | 168429726 |
| Appearance | Typically exists as solid at room temperature |
| LogP | 2 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 28 |
| Complexity | 514 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | BOPYJZYHIIFOOS-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H19N3O4/c1-28-18-8-6-15(7-9-18)19-12-17(10-11-22-19)20(25)23-13-14-2-4-16(5-3-14)21(26)24-27/h2-12,27H,13H2,1H3,(H,23,25)(H,24,26) |
| Chemical Name | N-(4-(hydroxycarbamoyl)benzyl)-2-(4-methoxyphenyl)isonicotinamide |
| Synonyms | HDAC-IN-57; HDAC-IN57; HDACIN-57; HDACIN57; HDAC IN 57 |
| 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
| Targets | HDAC1 2.07 nM (IC50) HDAC2 4.71 nM (IC50) HDAC6 2.4 nM (IC50) HDAC8 107 nM (IC50) |
| ln Vitro | In solid tumor cell lines MGC-803, A549, and HCT-116, HDAC-IN-57 (Compound 5e) (1.0 μM, 2.5 μM, 5.0 μM; 48 hours) suppresses migration and invasion [1]. The proliferation of solid tumor cell lines MGC-803, A549, and HCT-116 is considerably inhibited by HDAC-IN-57 (1.0 μM, 2.5 μM, and 5.0 μM; 48 hours), with IC50 values of 0.45 μM, 1.48 μM, and 0.57 μM, respectively[1]. In MGC-803 and HCT-116 cells, HDAC-IN-57 (1.0 μM, 2.5 μM, 5.0 μM; 48 hours) causes apoptosis in a dose-dependent way [1]. In MGC-803 and HCT-116 cell lines, HDAC-IN-57 (1.0 μM, 2.5 μM, 5.0 μM; 48 hours) suppresses LSD1 and HDACs [1]. In MGC-803 and HCT-116 cell cycles, HDAC-IN-57 (1.0 μM, 2.5 μM, 5.0 μM; 48 hours) causes G2/M phase arrest [1]. In vitro, HDAC-IN-57 exhibits good metabolic stability. retains 86.1% and 87.4% of the parent molecule in human liver microsomes (HLM) and rat liver microsomes (RLM), respectively, after an hour of incubation, with a T1/2 greater than 120 minutes [1]. |
| ln Vivo | HDAC-IN-57 (Compound 5e) (1 mg/kg IV, 10 mg/kg PO) showed an oral bioavailability (F%) of 10.6% and T1/2 of 0.37 hours (IV) and 2.75 hours (OR)[1]. In the NOD-SCID mouse MGC-803 xenograft model, HDAC-IN-57 (gavaged at 25 or 50 mg/kg, once daily for 21 days) achieved dose-dependent suppression of tumor growth [1]. |
| Cell Assay |
Western Blot Analysis[1] Cell Types: MGC-803 cells, HCT-116 cells Tested Concentrations: 1.5 μM Incubation Duration: 48 hrs (hours) Experimental Results: Inhibited cellular LSD1 and HDACs. Upregulated the expression of apoptotic markers, including cytochrome C, Bax, cleaved caspase-3/7/9, and cleaved PARP, while downregulating the expression of anti-apoptotic protein Bcl-2. Apoptosis Analysis[1] Cell Types: MGC-803 cells, HCT-116 cells Tested Concentrations: 1.0 μM, 2.5 μM, 5.0 μM Incubation Duration: 48 hrs (hours) Experimental Results: Triggered MGC-803 and HCT116 cells apoptosis in a dose-dependent manner. Induced about 55.4% and 51.5% MGC-803 cell apoptosis at a concentration of 5 μM. Cell Migration Assay [1] Cell Types: MGC-803 cells, HCT-116 cells Tested Concentrations: 1.0 μM, 2.0 μM, 4 μM Incubation Duration: 48 hrs (hours) Experimental Results: decreased the number of migrated of MGC-803 and HCT-116 cells. Inhibited the migration and invasion of cancer cells. Cell Cycle Analysis[1] Cell Types: MGC-803 cells, HCT-116 cells Tested Concentrations: 1.0 μM, 2.5 μM, 5.0 μM Incubation Duration: 48 hrs (hours) Experimental Results: Induced G2/M cycle arrest in MGC-803 and HCT-116 cells. |
| Animal Protocol |
Animal/Disease Models: MGC-803 xenograft model in NOD-SCID (severe combined immunodeficient) mouse[1] Doses: 25 or 50 mg/ kg Route of Administration: po (oral gavage); Experimental Results: Achieved a dose-dependent tumor growth inhibition (TGI) of 44.8% at 25 mg/kg and 71.5% at 50 mg/kg. Animal/Disease Models: Male SD rats (pharmacokinetic/PK assay)[1] Doses: 1 mg/kg; 10 mg/kg Route of Administration: intravenous (iv)injection; po (oral gavage) Experimental Results: pharmacokinetic/PK parameters for HDAC-IN-57 (Compound 5e) in SD rats[1] |
| References |
[1]. Discovery of novel, potent, and orally bioavailable HDACs inhibitors with LSD1 inhibitory activity for the treatment of solid tumors. Eur J Med Chem. 2023 Jun 5;254:115367. |
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 | 2.6498 mL | 13.2489 mL | 26.4978 mL | |
| 5 mM | 0.5300 mL | 2.6498 mL | 5.2996 mL | |
| 10 mM | 0.2650 mL | 1.3249 mL | 2.6498 mL |