PROTAC SOS1 degrader-6
PROTAC SOS1 degrader-6 is a selective SOS1 PROTAC degrader with a DC50 of 43-130 nM. PROTAC SOS1 degrader-6 induces ubiquitination and degradation of SOS1 via the ubiquitin-proteasome system by recruiting the E3 ligase VHL. PROTAC SOS1 degrader-6 reduces the levels of phosphorylated MEK and ERK. PROTAC SOS1 degrader-6 exerts antiproliferative effects in KRAS-driven cancer cells. PROTAC SOS1 degrader-6 can be used in research related to KRASG12C-mutant cancers and chronic myeloid leukemia.
(Pink: SOS1 ligand (HY-169371); Blue: VHL ligand (HY-125845); Black: linker (HY-W016456)).
For research use only. We do not sell to patients.
- CAS No.: 3032282-51-9
- Formula: C46H55F3N8O6S
- Molecular Weight:905.04
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
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VHL |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| K562 | IC50 |
0.535 μM
Compound: 23
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Antiproliferative activity against human K562 cells incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human K562 cells incubated for 72 hrs by CCK8 assay
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[PMID: 38316747] |
| MIA PaCa-2 | IC50 |
3479 nM
Compound: 23
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Antiproliferative activity against human MIA PaCa-2 cells incubated for 6 days by CCK8 assay
Antiproliferative activity against human MIA PaCa-2 cells incubated for 6 days by CCK8 assay
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[PMID: 38316747] |
| MIA PaCa-2 | IC50 |
98 nM
Compound: 23
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Antiproliferative activity against human MIA PaCa-2 cells incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human MIA PaCa-2 cells incubated for 72 hrs by CCK8 assay
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[PMID: 38316747] |
| NCI-H358 | IC50 |
2450 nM
Compound: 23
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Antiproliferative activity against human NCI-H358 cells incubated for 6 days by CCK8 assay
Antiproliferative activity against human NCI-H358 cells incubated for 6 days by CCK8 assay
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[PMID: 38316747] |
| SW837 | IC50 |
1035 nM
Compound: 23
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Antiproliferative activity against human SW837 cells incubated for 6 days by CCK8 assay
Antiproliferative activity against human SW837 cells incubated for 6 days by CCK8 assay
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[PMID: 38316747] |
PROTAC SOS1 degrader-6 (Compound 23) (0.003-10 μM; 24 h) potently induces dose-dependent degradation of SOS1 in K562 (DC50=130 nM), PANC-1 (DC50=43 nM), MIA PaCa-2 (DC50=61 nM) and NCI-H358 (DC50=50 nM) cell lines after 24 h of treatment[1].
PROTAC SOS1 degrader-6 (1 μM; 0.167-24 h) induces rapid and sustained SOS1 degradation in K562, PANC-1, MIA PaCa-2 and NCI-H358 cell lines at a treatment concentration of 1 μM, with the degradation effect peaking within 4 h and showing no rebound within 96 h[1].
PROTAC SOS1 degrader-6 is a highly selective SOS1 degrader in the MIA PaCa-2 cell line, which exerts no significant effect on the abundance of other cellular proteins including SOS2[1].
PROTAC SOS1 degrader-6 (0-3 μM) downregulates the levels of pMEK and pERK in K562 cell lines via degrading SOS1, thereby inhibiting signal transduction of the RAS-MAPK pathway[1].
PROTAC SOS1 degrader-6 (3-10 days) exhibits significant antiproliferative activity in K562, MIA PaCa-2 (IC50 = 98 nM) and NCI-H358 cell lines[1].
PROTAC SOS1 degrader-6 (1-10 μM) sensitizes KRASG12C-mutant NCI-H358, MIA PaCa-2 and SW837 cell lines to AMG510 (HY-114277), induces a synergistic antiproliferative effect, enhances inhibition of the RAS-MAPK pathway, and increases the level of cell apoptosis[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:K562 (wild-type KRAS), PANC-1 (KRASG12D), MIA PaCa-2 (KRASG12C), NCI-H358 (KRASG12C)
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Concentration:0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10 μM
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Incubation Time:24 h
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Result:Induced dose-dependent SOS1 degradation across all tested cell lines, with over 90% maximum degradation achieved in each line.
Achieved half-maximal degradation concentrations (DC50) of 130 nM in K562 cells, 43 nM in PANC-1 cells, 61 nM in MIA PaCa-2 cells, and 50 nM in NCI-H358 cells.
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Cell Line:K562 (wild-type KRAS), PANC-1 (KRASG12D), MIA PaCa-2 (KRASG12C), NCI-H358 (KRASG12C)
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Concentration:1 μM
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Incubation Time:0.167, 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24 h
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Result:Induced rapid SOS1 degradation, with measurable reduction in SOS1 levels within 1 h and maximum degradation reached by 4 h in most tested cell lines.
Prevented SOS1 protein levels from rebounding even after 96 h of treatment.
| Species | Dose | Route | T1/2 | AUC0-∞ | Cmax | AUC0-t |
|---|---|---|---|---|---|---|
| Mice[1] | 10 mg/kg | i.p. | 4.19 h | 4277 ng·h/mL | 1650 ng/mL | 4259 ng·h/mL |
PROTAC SOS1 degrader-6 (i.p.; 30 mg/kg; once daily; for 28 days) induces mild growth inhibition (TGI 11.4%) in NCI-H358 xenograft tumors. When combined with AMG510 (p.o.; 10 mg/kg; once daily; for 28 days), it produces a synergistic effect with a tumor growth inhibition rate of 78.8%, and no toxicity is detected[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD-SCID (male, 6 weeks old, 18−20 g, K562 cell xenograft model)[1]
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Dosage:5 mg/kg (tumor inhibition); 25 mg/kg (tumor inhibition; SOS1 degradation)
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Administration:i.p.; 5 days on/2 days off; 21 days; i.p.; single dose
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Result:Inhibited tumor growth by 56.3% compared to vehicle control.
Inhibited tumor growth by 72.3% compared to vehicle control.
Reduced SOS1 protein levels in tumor tissues by ~70% relative to control.
Caused no significant body weight loss during treatment.
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Animal Model:BALB/c nude (male, 5 weeks old, 20−22 g, NCI-H358 cell xenograft model)[1]
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Dosage:30 mg/kg (monotherapy TGI); 30 mg/kg (combination TGI with AMG510 10 mg/kg)
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Administration:i.p.; daily; 28 days
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Result:Achieved a tumor growth inhibition (TGI) of 11.4% as monotherapy.
Achieved a tumor growth inhibition (TGI) of 78.8% in combination with 10 mg/kg AMG510, a significant enhancement over either monotherapy.
Caused no significant body weight loss during any treatment.
Chemical Information
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CAS No. 3032282-51-9
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Molecular Weight 905.04
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Formula C46H55F3N8O6S
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SMILES
CC1=NC2=C(C=C(C(OC)=C2)OCCCCC(N[C@@H](C(C)(C)C)C(N3C[C@H](O)C[C@H]3C(NCC4=CC=C(C5=C(C)N=CS5)C=C4)=O)=O)=O)C(N[C@H](C)C6=CC(N)=CC(C(F)(F)F)=C6)=N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC SOS1 degrader-6 Related Classifications
HY-162281 Related Classifications
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