Physicochemical Properties
| Molecular Formula | C34H41NO7 |
| Molecular Weight | 575.691850423813 |
| Exact Mass | 575.288 |
| CAS # | 2690312-67-3 |
| PubChem CID | 156831801 |
| Appearance | White to light yellow solid powder |
| LogP | 5.3 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 42 |
| Complexity | 1240 |
| Defined Atom Stereocenter Count | 11 |
| SMILES | C[C@]12C(C=C[C@@H]([C@@]31O[C@]3([H])C[C@@]1([H])[C@]3([H])CC[C@@]([H])([C@]3(CC[C@]21[H])C)[C@@H]([C@]1([H])OC(C(=C(C1)C)CO)=O)C)OC(C1N=CC=CC=1)=O)=O |
| InChi Key | VLOZRPFAQLWDLI-RJMVMCCISA-N |
| InChi Code | InChI=1S/C34H41NO7/c1-18-15-26(40-30(38)21(18)17-36)19(2)22-8-9-23-20-16-29-34(42-29)28(41-31(39)25-7-5-6-14-35-25)11-10-27(37)33(34,4)24(20)12-13-32(22,23)3/h5-7,10-11,14,19-20,22-24,26,28-29,36H,8-9,12-13,15-17H2,1-4H3/t19-,20-,22+,23-,24-,26+,28-,29+,32+,33-,34+/m0/s1 |
| Chemical Name | [(1S,2R,6S,7S,9R,11S,12S,15R,16S)-15-[(1S)-1-[(2R)-5-(hydroxymethyl)-4-methyl-6-oxo-2,3-dihydropyran-2-yl]ethyl]-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-6-yl] pyridine-2-carboxylate |
| 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 | The viability of HCT116 and SW620 cells is decreased by ASR-490 (0-1.6 µM; 24 hours, 48 hours) at 24 hours (IC50 = 750 nM in HCT116 cells, IC50 = 1.2 µM in SW620 cells) and 48 hours (in HCT116 cells, IC50 = 850 nM in SW620 cells) [1]. ASR-490 (750 nM in HCT116 cells, 1.2 µM in SW620 cells, 24 hours) inhibits colorectal cancer cells and exhibits apoptotic cell death and induction of pro-apoptotic markers Bax and cleaved PARP expression [1]. Notch1 overexpression is eliminated by ASR-490 (HCT116 cells; 750 nM over 24 hours, 600 nM over 48 hours), which also prevents HCT/Notch1 transfectants from growing [1]. |
| ln Vivo | ASR-490 (5 mg/kg; i.p.; three times per week for 4 weeks) suppresses control (pCMV/HCT116) and Notch1/HCT116 tumor growth in xenograft mice [1]. |
| Cell Assay |
Cell viability assay [1] Cell Types: HCT116, SW620 Cell Tested Concentrations: 0-1.6 µM Incubation Duration: 24 hrs (hours), 48 hrs (hours) Experimental Results: The viability of HCT116 and SW620 cells diminished within 24 hrs (hours) (IC50 =750 nM in HCT116 cells, IC50 = 1.2 µM in SW620 cells) and 48 hrs (hours) (IC50 = 600 nM in HCT116 cells, IC50 = 850 nM in SW620 cells). Apoptosis analysis[1] Cell Types: HCT116, SW620 Cell Tested Concentrations: 750 nM in HCT116 cells, 1.2 µM in SW620 cells Incubation Duration: 24 hrs (hours) Experimental Results: Shows apoptotic cell death and upregulation of pro-apoptotic markers Bax and cleavage PARP expression and inhibitory capacity in colorectal cancer cells. Cell proliferation experiment [1] Cell Types: HCT116 cell Tested Concentrations: 750 nM in 24 h, 600 nM in 48 h Incubation Duration: 24 h, 48 h Experimental Results: Overcome Notch1 overexpression and inhibit the growth of HCT/Notch1 transfectants. |
| Animal Protocol |
Animal/Disease Models: 6- to 8weeks old BALB/c athymic nude mice (nu/nu) (pCMV/HCT116 and Notch1/HCT116 (C4) xenografts) [1]. Doses: 5 mg/kg Route of Administration: intraperitoneal (ip) injection three times per week for 4 weeks Experimental Results: Inhibition of Notch1/HCT116 tumor growth in control (pCMV/HCT116) and xenograft mice. |
| References |
[1]. ASR490, a Small Molecule, Overrides Aberrant Expression of Notch1 in Colorectal Cancer. Mol Cancer Ther. 2020; 19(12):2422-2431. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~25 mg/mL (~43.43 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (4.34 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7370 mL | 8.6852 mL | 17.3705 mL | |
| 5 mM | 0.3474 mL | 1.7370 mL | 3.4741 mL | |
| 10 mM | 0.1737 mL | 0.8685 mL | 1.7370 mL |