| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
SHP2 protein degrader-2 targets SHP2 for proteasomal degradation. It acts as a PROTAC, bringing SHP2 into proximity with an E3 ubiquitin ligase, leading to ubiquitination and subsequent degradation of the SHP2 protein.
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|---|---|
| ln Vitro |
For MV4;11 and KYSE520 cells, respectively, SHP2 Protein Degrader-2 (SHP2-D26) achieves good degradation of SHP2, with DC50 values (concentration at which 50% of the protein is degraded) of 2.6 nM and 6.0 nM [1].
In MV4;11 and KYSE520 cancer cells, SHP2 protein degrader-2 achieves potent degradation of SHP2 with DC50 values of 2.6 nM and 6.0 nM, respectively. It reduces SHP2 expression levels across various cancer cell types, leading to antiproliferative effects. |
| ln Vivo |
Dedicated in vivo efficacy studies for this specific degrader are not extensively documented in standard profiles. As a PROTAC with potent DC50 values in the low nanomolar range, it is expected to demonstrate in vivo efficacy in tumor xenograft models.
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| Enzyme Assay |
SHP2 degradation is measured by Western blot. Cancer cells are treated with varying concentrations of SHP2 protein degrader-2 for a specified time (e.g., 6-24 hours). Cells are lysed, and SHP2 protein levels are quantified. The DC50 (concentration for 50% protein degradation) is calculated.
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| Cell Assay |
Cancer cell lines (e.g., MV4;11, KYSE520) are cultured in appropriate media. Cells are treated with SHP2 protein degrader-2 across a concentration range (0.1 nM to 1 uM). Cell viability is measured using CellTiter-Glo assay. For degradation studies, cells are harvested after treatment and analyzed by Western blot.
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| Animal Protocol |
In vivo protocols would typically involve establishing subcutaneous tumor xenografts of cancer cell lines in immunodeficient mice. Once tumors reach a certain size, mice would be administered SHP2 protein degrader-2 via intraperitoneal or intravenous injection. Tumor tissues would be harvested for SHP2 protein level analysis.
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| ADME/Pharmacokinetics |
Detailed PK parameters for SHP2 protein degrader-2 are not extensively documented. As a PROTAC with high molecular weight (approx. 1100-1200 g/mol), it is typically administered via parenteral routes for in vivo studies due to expected poor oral bioavailability.
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| Toxicity/Toxicokinetics |
SHP2 protein degrader-2 is a PROTAC degrader, a relatively new class of therapeutics. Comprehensive toxicology studies are not available in standard profiles. As with other molecularly targeted agents, on-target and off-target toxicity would need to be evaluated.
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| References | |
| Additional Infomation |
SHP2 is an important node in the RAS signaling pathway and is a validated target for cancer therapy. Unlike traditional inhibitors, PROTAC degraders like SHP2-D26 remove the entire protein, potentially overcoming resistance mutations and providing sustained target inhibition. It is not an approved drug.
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| Molecular Formula |
C56H79CLN12O6S2
|
|---|---|
| Molecular Weight |
1115.89
|
| Exact Mass |
1114.537
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| CAS # |
2740582-16-3
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| PubChem CID |
163408836
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| Appearance |
White to off-white solid powder
|
| LogP |
6.2
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
23
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| Heavy Atom Count |
77
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| Complexity |
1920
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
C(N1C[C@H](C[C@@H]1C(=O)N[C@@H](C1C=CC(C2=C(N=CS2)C)=CC=1)C)O)(=O)[C@@H](C(C)(C)C)NC(=O)CCCCCCCCN1CCN(CC1)C(=O)CCC(=O)NC1C=CC=C(C=1Cl)SC1=NC=C(N2CCC(CC2)(N)C)N=C1N
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| InChi Key |
XJSPAQRZSJUBLB-ISSNAGQGSA-N
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| InChi Code |
InChI=1S/C56H79ClN12O6S2/c1-36(38-17-19-39(20-18-38)49-37(2)61-35-76-49)62-52(74)42-32-40(70)34-69(42)54(75)50(55(3,4)5)65-45(71)16-11-9-7-8-10-12-25-66-28-30-68(31-29-66)47(73)22-21-46(72)63-41-14-13-15-43(48(41)57)77-53-51(58)64-44(33-60-53)67-26-23-56(6,59)24-27-67/h13-15,17-20,33,35-36,40,42,50,70H,7-12,16,21-32,34,59H2,1-6H3,(H2,58,64)(H,62,74)(H,63,72)(H,65,71)/t36-,40+,42-,50+/m1/s1
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| Chemical Name |
(2R,4S)-1-[(2R)-2-[9-[4-[4-[3-[3-amino-5-(4-amino-4-methylpiperidin-1-yl)pyrazin-2-yl]sulfanyl-2-chloroanilino]-4-oxobutanoyl]piperazin-1-yl]nonanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1R)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~89.61 mM)
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|---|---|
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8961 mL | 4.4807 mL | 8.9615 mL | |
| 5 mM | 0.1792 mL | 0.8961 mL | 1.7923 mL | |
| 10 mM | 0.0896 mL | 0.4481 mL | 0.8961 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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