Physicochemical Properties
| Molecular Formula | C52H57CLFN9O6 |
| Molecular Weight | 958.52 |
| Appearance | Typically exists as solid at room temperature |
| 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 | In JeKo-1 cells, PROTAC BTK Degrader-5 (Compound 3e) (1.6~1000 nM; 24 h) causes BTK degradation with a DC50 value of 7.0 nM[1]. With a half-life of 145 minutes, PROTAC BTK Degrader-5 (100 and 1000 nM) exhibits metabolic stability [1]. The proteasome inhibitor MG-132 (HY-13259) (5.0 μM) effectively blocks BTK degradation produced by PROTAC BTK Degrader-5 (100 nM; 12 h) [1]. PROTAC BTK Degrader-5 (1.6~1000 nM; 24 h) does not degrade GSPT1 or IKZF1, although it does degrade IKZF3 somewhat [1]. The anti-proliferative effects of PROTAC BTK Degrader-5 (72 h) are observed in OCI-ly10, TMD8, JeKo-1, and BTKC481S Ba/F3 cells. The effect is greater than that of Ibrutinib (HY-10997), whose IC50 values are 4.5, 4.7, 79.8, and 1546.0 nM, respectively[1]. The IC50 values are 2.3, 4.5, 38.1, and 86.0 nM, respectively. |
| ln Vivo | In mice, PROTAC BTK Degrader-5 (2 mg/kg, intravenous injection, single dose) exhibits metabolic stability [1]. |
| Animal Protocol |
Animal/Disease Models: The male balb/c (Bagg ALBino) mouse[1] Doses: a single dose 2 mg/kg or 100 mg/kg, 5% DMSO, 10% Solutol, 85% saline Route of Administration: intravenous (iv) injection; po (oral gavage) (po ) Experimental Results: Maintained above 10 nM for at least 4 h after administration of PROTAC BTK Degrader-5 at a single dose of 2 mg/kg via intravenous (iv) (IV) injection in the plasma (the effective BTK degradation DC5050 = 7.0nM). Had poor oral bioavailability at a dose of 100 mg/kg. |
| References |
[1]. Discovery of novel BTK PROTACs with improved metabolic stability via linker rigidification strategy. European Journal of Medicinal Chemistry.Volume 255, 5 July 2023, 115403. |
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 | 1.0433 mL | 5.2164 mL | 10.4328 mL | |
| 5 mM | 0.2087 mL | 1.0433 mL | 2.0866 mL | |
| 10 mM | 0.1043 mL | 0.5216 mL | 1.0433 mL |