Physicochemical Properties
| Molecular Formula | C42H51CL2N11O8 |
| Molecular Weight | 908.83 |
| Exact Mass | 907.329 |
| CAS # | 2624181-69-5 |
| PubChem CID | 162641701 |
| Appearance | Light yellow to yellow solid powder |
| LogP | 2.2 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 22 |
| Heavy Atom Count | 63 |
| Complexity | 1520 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PVZCLGQITBYVPH-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C42H51Cl2N11O8/c1-42(10-13-53(14-11-42)33-25-47-37(38(45)49-33)29-5-2-6-30(43)36(29)44)48-24-27-26-54(52-51-27)15-17-61-19-21-63-23-22-62-20-18-60-16-12-46-31-7-3-4-28-35(31)41(59)55(40(28)58)32-8-9-34(56)50-39(32)57/h2-7,25-26,32,46,48H,8-24H2,1H3,(H2,45,49)(H,50,56,57) |
| Chemical Name | 4-[2-[2-[2-[2-[2-[4-[[[1-[6-amino-5-(2,3-dichlorophenyl)pyrazin-2-yl]-4-methylpiperidin-4-yl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione |
| 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 | SHP2[1] |
| ln Vitro | Compound SP4, or SHP2 protein degrader-1, has a growth inhibitory effect on Hela cells with an IC50 of 5.77 and 4.30 nM, respectively, over a 24-hour period. This is approximately 100 times more active than SHP099, a SHP2 inhibitor [1]. Compound SP4, or SHP2 protein degrader-1, causes 54.01% apoptotic death at concentrations of 0–200 μM over a period of 96 hours, as opposed to 0.13% at 100 nM. Compound SP4, or SHP2 protein degrader-1, can cause cell cycle arrest in Hela cells at the G1 phase (100-200 μM) in 96 hours[1]. Compound SP4 (SHP2 protein degrader-1; 0-200 μM; 96 hours) strongly suppresses JNK, Erk, and p38 phosphorylation[1]. Through a mechanism involving the inhibition of SHP2 catalytic activity, SHP2 protein degrader-1 (compound SP4) (0-200 μM; 96 hours) inhibits RAS/MAPK signaling and cellular responses[1]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: Hela cells Tested Concentrations: 0-200 μM Incubation Duration: 24 hrs (hours) Experimental Results: Strongly inhibited the growth of Hela cells, with IC50 of 5.77 and 4.30 nM, respectively, which were about 100 times higher than the activity of SHP099 (SHP2 inhibitor). Apoptosis Analysis[1] Cell Types: Hela cells Tested Concentrations: 0-100 μM Incubation Duration: 96 hrs (hours) Experimental Results: Induced 54.01% apoptotic death compared with 0.13% of the control at 100 nM. While SHP099 at 1000 nM could induce 33.74% apoptotic death compared with 0.13% of the control. Cell Cycle Analysis[1] Cell Types: Hela cells Tested Concentrations: 0 -100 μM Incubation Duration: 96 hrs (hours) Experimental Results: Induced cell cycle arrested at the G1 phase in Hela cells. Western Blot Analysis[1] Cell Types: Hela cells Tested Concentrations: 0-100 μM Incubation Duration: 96 hrs (hours) Experimental Results: Dramatically inhibited the phosphorylation of JNK, Erk and p38. |
| References |
[1]. Novel PROTACs for degradation of SHP2 protein. Bioorg Chem. 2021;110:104788. |
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 | 1.1003 mL | 5.5016 mL | 11.0032 mL | |
| 5 mM | 0.2201 mL | 1.1003 mL | 2.2006 mL | |
| 10 mM | 0.1100 mL | 0.5502 mL | 1.1003 mL |