Physicochemical Properties
| Molecular Formula | C29H27F3N2O2 |
| Molecular Weight | 492.53 |
| Exact Mass | 492.202 |
| CAS # | 2235396-63-9 |
| PubChem CID | 135230895 |
| Appearance | Brown to reddish brown solid powder |
| LogP | 4.1 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 36 |
| Complexity | 777 |
| Defined Atom Stereocenter Count | 2 |
| SMILES | C1(C2=CC(F)=C([C@@H]3C4=C(C[C@@H](C)N3CC(F)(C)C)C3=C(N4)C=CC=C3)C(F)=C2)=CC=C(C(O)=O)C=C1 |
| InChi Key | XKYAKCQZMYWSSE-CHAGWJKLSA-N |
| InChi Code | InChI=1S/C29H27F3N2O2/c1-16-12-21-20-6-4-5-7-24(20)33-26(21)27(34(16)15-29(2,3)32)25-22(30)13-19(14-23(25)31)17-8-10-18(11-9-17)28(35)36/h4-11,13-14,16,27,33H,12,15H2,1-3H3,(H,35,36)/t16-,27-/m1/s1 |
| Chemical Name | 4-[3,5-difluoro-4-[(1R,3R)-2-(2-fluoro-2-methylpropyl)-3-methyl-1,3,4,9-tetrahydropyrido[3,4-b]indol-1-yl]phenyl]benzoic acid |
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | ERα 4.6 nM (IC50) |
| ln Vitro | ERα degrader-2 (0.01-40 nM) lowers ERα expression and not entirely destroys ERα in MCF-7 cells even at a higher biological dose in MCF7 cells[1]. |
| ln Vivo | In mice, ERα degrader-2 (oral; 2–6 mg/kg; QD; 21 days) significantly inhibits tumor growth and reduces tumor volume[1]. The pharmacokinetic parameters of ERα degrader-2 (oral gavage; 2 mg/kg; single dosage) are superior to those of AZD9496. Its half-life period is 12.1 hours, its plasma exposure (AUC) is 16073.7 h*ng/mL, and its oral availability is 80.5%[1]. |
| Animal Protocol |
Animal/Disease Models: MCF-7 human breast cancer xenograft model in nude mice[1] Doses: 2 mg/kg; 6 mg/kg Route of Administration: Oral administration; 2-6 mg/kg; QD; 21 days Experimental Results: demonstrated in vivo efficacy in breast cancer xenograft model. |
| References |
[1]. Dynamics-Based Discovery of Novel, Potent Benzoic Acid Derivatives as Orally Bioavailable Selective Estrogen Receptor Degraders for ERα+ Breast Cancer. J Med Chem. |
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 | 2.0303 mL | 10.1517 mL | 20.3033 mL | |
| 5 mM | 0.4061 mL | 2.0303 mL | 4.0607 mL | |
| 10 mM | 0.2030 mL | 1.0152 mL | 2.0303 mL |