PROTAC SOS1 degrader-1 TFA
Based on 1 Customer Validation
PROTAC SOS1 degrader-1 TFA is a degrader of SOS1 PROTAC, with a DC50 of 98.4 nM and a Kd value of 44 nM. PROTAC SOS1 degrader-1 TFA induces the formation of a ternary complex with SOS1 and the VCB E3 ubiquitin ligase complex, thereby promoting the ubiquitination and proteasomal degradation of SOS1. PROTAC SOS1 degrader-1 TFA reduces KRAS-GTP levels, inhibits the phosphorylation of ERK in the RAS-RAF-MEK-ERK pathway, and suppresses the proliferation of cancer cells carrying KRAS mutations. PROTAC SOS1 degrader-1 TFA inhibits tumor growth in mouse xenograft models. PROTAC SOS1 degrader-1 TFA can be used for the research of KRAS-driven cancers.
(Pink: SOS1 ligand (HY-111671); Blue: VHL ligand (HY-112078); Black: linker).
For research use only. We do not sell to patients.
- Purity: 98.38%
- Formula: C59H77ClF4N10O6S
- Molecular Weight:1165.82
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Storage:
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Biological Activity
DC50: 98.4 nM (SOS1)[1]
PROTAC SOS1 degrader-1 (Compound 9d) (contact time: 120 s, dissociation time: 240 s) TFA forms a ternary complex with highly positive cooperativity with SOS1 and VCB proteins, with a cooperativity factor of 15.1, a binary KD value of 56.0 nM, and a ternary KD value of 3.7 nM[1].
PROTAC SOS1 degrader-1 (0-2000 nM; 24 h) TFA induces dose-dependent degradation of SOS1 in NCI-H358 cells, with a DC50 of 98.4 nM, and achieves a degradation rate of 92.5% after treatment at 1 μM for 24 h[1].
PROTAC SOS1 degrader-1 (1 μM; 1-24 h) TFA induces time-dependent degradation of SOS1 in NCI-H358 cells (peaking at 24 h) and AsPC-1 cells (peaking at 16 h)[1].
PROTAC SOS1 degrader-1 (7 days) TFA inhibits 3D proliferation of human cancer cells harboring KRASG12C, KRASG12D, KRASG12V, and KRASG12S mutations, with IC50 values ranging from 0.115 to 0.525 μM after 7 days of treatment, but exerts no inhibitory effect on the proliferation of CAL-62 or 293T cells[1].
PROTAC SOS1 degrader-1 (1 μM; 1-24 h) TFA transiently increases pERK levels in NCI-H358 cells, followed by inhibition of ERK phosphorylation; it exhibits an IC50 of 72.3 nM for pERK inhibition after 24 hours of treatment[1].
Treatment with PROTAC SOS1 degrader-1 TFA for 24 h reduces the level of activated KRAS-GTP in NCI-H358 cells in a dose-dependent manner[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:NCI-H358 cells
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Concentration:7.8, 15.6, 31.2, 62.5, 125, 250, 500, 1000, 2000 nM
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Incubation Time:24 h
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Result:Induced 56.2% SOS1 degradation at 0.1 μM.
Induced 92.5% SOS1 degradation at 1 μM.
Had a half-maximal degradation concentration (DC50) of 98.4 nM, with near-complete degradation at higher concentrations.
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Cell Line:NCI-H358, AsPC-1 cells
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Concentration:1 μM
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Incubation Time:1, 2, 4, 6, 8, 12, 14, 16, 24 h
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Result:Caused significant SOS1 degradation in NCI-H358 cells at 4 hours, with degradation peaking at 24 hours.
Caused SOS1 degradation in AsPC-1 cells that peaked at 16 hours.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:BALB/c nude mice (6-8 weeks old; subcutaneously injected with 1 × 107 NCI-H358 cells)[1]
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Dosage:10 mg/kg; 20 mg/kg
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Administration:i.p.; daily; 21 days
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Result:Inhibited tumor growth by 72.5% (P < 0.001).
Inhibited tumor growth by 86.1% (P < 0.001).
Caused no statistically significant body weight loss.
Achieved persisted SOS1 degradation and pERK inhibition in harvested tumor xenografts.
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Animal Model:BALB/c nude mice (6-8 weeks old; subcutaneously injected with 5 × 106 NCI-H358 cells)[1]
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Dosage:20 mg/kg; 50 mg/kg
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Administration:intratumoral injection; twice weekly; 35 days
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Result:Resulted in significant tumor growth inhibition.
Caused no body weight loss during the study.
Achieved persisted SOS1 degradation and pERK inhibition in harvested tumor xenografts.
Chemical Information
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Appearance Solid
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Molecular Weight 1165.82
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Formula C59H77ClF4N10O6S
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Color White to off-white
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SMILES
O=C([C@H]1N(C([C@@H](NC(CCCCCCCCN2CCN(C3=C4C(N(CC5=CC(C)=C(F)C(C)=C5)C(N6CC7(CNC7)C6)=N4)=CC(Cl)=C3)CC2)=O)C(C)(C)C)=O)C[C@H](O)C1)N[C@H](C8=CC=C(C9=C(C)N=CS9)C=C8)C.OC(C(F)(F)F)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture and light
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light)
Solvent & Solubility
DMSO : 100 mg/mL (85.78 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (279 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 0.8578 mL | 4.2888 mL | 8.5777 mL | 21.4441 mL |
| 5 mM | 0.1716 mL | 0.8578 mL | 1.7155 mL | 4.2888 mL | |
| 10 mM | 0.0858 mL | 0.4289 mL | 0.8578 mL | 2.1444 mL | |
| 15 mM | 0.0572 mL | 0.2859 mL | 0.5718 mL | 1.4296 mL | |
| 20 mM | 0.0429 mL | 0.2144 mL | 0.4289 mL | 1.0722 mL | |
| 25 mM | 0.0343 mL | 0.1716 mL | 0.3431 mL | 0.8578 mL | |
| 30 mM | 0.0286 mL | 0.1430 mL | 0.2859 mL | 0.7148 mL | |
| 40 mM | 0.0214 mL | 0.1072 mL | 0.2144 mL | 0.5361 mL | |
| 50 mM | 0.0172 mL | 0.0858 mL | 0.1716 mL | 0.4289 mL | |
| 60 mM | 0.0143 mL | 0.0715 mL | 0.1430 mL | 0.3574 mL | |
| 80 mM | 0.0107 mL | 0.0536 mL | 0.1072 mL | 0.2681 mL |
PROTAC SOS1 degrader-1 TFA Related Classifications
HY-145737A Related Classifications
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