| ln Vitro |
Aurora kinase/HDAC-IN-1 (compound 6) (0.64 nM-10 μM; 72 h) inhibited the proliferation of HCT-116 and MIA PaCa-2 cells, with IC50 values of 30.2 nM and 42.8 nM, respectively [1]. Aurora kinase/HDAC-IN-1 (30-120 nM; 24 h) induced G2/M phase arrest in HCT-116 cells [1]. Aurora kinase/HDAC-IN-1 (30-120 nM; 48 h) induced apoptosis in HCT-116 cells [1]. Aurora kinase/HDAC-IN-1 (30-120 nM; 72 h) regulated Aurora/HDAC-related signaling in HCT-116 cells, including promoting Ac-H3 and inhibiting Aurora A phosphorylation [1].
|
|---|---|
| ln Vivo |
Aurora kinase/HDAC-IN-1 (compound 6) (50-150 mg/kg/d; po to wound; once daily QD; for 21 consecutive days) significantly inhibited tumor growth in the HCT-116 rectal cancer xenograft model (TGI = 71.8% at 150 mg/kg/d) and showed better external bioavailability in the model (F = 23.2%) [1].
|
| Cell Assay |
Cell Viability Assay[1]
Cell Types: HCT-116 cells; MIA PaCa-2 cells Tested Concentrations: 0.64 nM-10 μM Incubation Duration: 72 h Experimental Results: Inhibited HCT-116 cell proliferation with an IC50 value of 30.2 nM. Inhibited MIA PaCa-2 cell proliferation with an IC50 value of 42.8 nM. Cell Cycle Analysis[1] Cell Types: HCT-116 cells Tested Concentrations: 30 nM, 60 nM, 120 nM Incubation Duration: 24 h Experimental Results: Increased G2/M-phase population from 5.03% (control) to 12.68% (30 nM), 20.17% (60 nM), and 25.40% (120 nM). Apoptosis Analysis[1] Cell Types: HCT-116 cells Tested Concentrations: 30 nM, 60 nM, 120 nM Incubation Duration: 48 h Experimental Results: Increased apoptosis rate from 1.99% (control) to 21.03% (30 nM), 42.81% (60 nM), and 59.13% (120 nM). Western Blot Analysis[1] Cell Types: HCT-116 cells Tested Concentrations: 30 nM, 60 nM, 120 nM Incubation Duration: 72 h Experimental Results: Increased Ac-H3 expression and upregulated p53 and Caspase 3 expression, and reduced p-Aurora A levels. |
| Animal Protocol |
Animal/Disease Models: Female BALB/c nude mice (6-8 weeks old) bearing subcutaneous HCT-116 xenografts [1]
Doses: 50 mg/kg/d, 150 mg/kg/d Route of Administration: Oral gavage (p.o.), once daily (QD), for 21 days. Experimental Results: Inhibited tumor growth in HCT-116 colorectal cancer xenograft mice, resulting in a significant reduction in tumor volume without obvious toxicity. Increased tumor necrosis and reduced Ki67 staining (decreased proliferation), with more pronounced effects at 150 mg/kg/d. |
| References |
| Exact Mass |
449.143
|
|---|---|
| CAS # |
2727102-12-5
|
| PubChem CID |
156894795
|
| Appearance |
Typically exists as solids at room temperature
|
| Hydrogen Bond Donor Count |
4
|
| Rotatable Bond Count |
7
|
| Heavy Atom Count |
32
|
| Complexity |
609
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
IPSHRTLGOBYBHK-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H20FN7OS/c1-13-10-20(30-29-13)27-19-8-9-25-22(28-19)32-12-14-2-4-15(5-3-14)21(31)26-18-7-6-16(23)11-17(18)24/h2-11H,12,24H2,1H3,(H,26,31)(H2,25,27,28,29,30)
|
| Chemical Name |
N-(2-amino-4-fluorophenyl)-4-[[4-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylmethyl]benzamide
|
| 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)
|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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