SOS1-IN-27
SOS1-IN-27 is a potent, selective allosteric SOS1 inhibitor with a KD of 14 nM and SOS1-KRAS binding IC50 of 1.6 nM. SOS1-IN-27 disrupts SOS1-KRAS interaction, inhibits MAPK/PI3K signaling, induces G1 arrest and tumor cell apoptosis. SOS1-IN-27 serves as a valuable tool compound for pan-KRAS-driven colorectal cancer studies.
For research use only. We do not sell to patients.
- Formula: C32H43N5
- Molecular Weight:497.72
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
p38 MAPK |
SOS1 14 nM (Kd) |
SOS1-KRAS 1.6 nM (IC50) |
PI3K |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| SW-620 | IC50 |
0.68 μM
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Inhibits SW-620 cells growth for 120 h
Inhibits SW-620 cells growth for 120 h
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42247371 |
| SW837 | IC50 |
0.5 μM
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Inhibits SW837 cells growth for 120 h
Inhibits SW837 cells growth for 120 h
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42247371 |
| GP2D cell | IC50 |
0.2 μM
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Inhibits GP2D cells growth for 120 h
Inhibits GP2D cells growth for 120 h
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42247371 |
| HCT-116 | IC50 |
0.47 μM
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Inhibits HT-116 cells growth for 120 h
Inhibits HT-116 cells growth for 120 h
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42247371 |
| SW480 | IC50 |
0.52 μM
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Inhibits SW480 cells growth for 120 h
Inhibits SW480 cells growth for 120 h
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42247371 |
| HT-29 | IC50 |
0.56 μM
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Inhibits HT-29 cells growth for 120 h
Inhibits HT-29 cells growth for 120 h
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42247371 |
| RKO | IC50 |
0.31 μM
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Inhibits RKO cells growth for 120 h
Inhibits RKO cells growth for 120 h
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42247371 |
In Vitro
SOS1-IN-27 (78d) potently blocks SOScat-catalyzed nucleotide exchange of wild-type and mutant KRAS with IC50 values of 11 nM (wild-type), 7.0 nM (G12C), 8.1 nM (G12V), and 17 nM (G12D), while exhibiting negligible EGFR inhibitory activity even at 1 μM and thus demonstrating outstanding EGFR kinase selectivity[1].
SOS1-IN-27 (10 μM; 40 min) significantly improves the thermal stability of SOScat[1].
SOS1-IN-27 binds SOS1 to disrupt SOS1-KRAS interaction, showing reduced fluorescence polarization (FP=83 mP) and potent SOS1-KRASG12C binding inhibition (IC50=1.6 nM)[1].
SOS1-IN-27 (120 h) demonstrates potent inhibitory activity across all tested CRC cell lines (IC50 of 93-321 nM) in 3D cell culture, which is stronger than that in 2D cell culture[1].
SOS1-IN-27 (0.2-0.8 μM; 14 days) effectively inhibits the clonogenicity of SW620 and HCT116 cells[1].
SOS1-IN-27 (2-8 μM; 48 h) induces apoptosis and G1-phase cell cycle arrest in SW620 and HCT116 cells[1].
SOS1-IN-27 (0.5-2 μM; 72 h) modulates the expression of critical cell cycle regulatory proteins in SW620 and HCT116 cells[1].
SOS1-IN-27 (0.5-2 μM; 72 h) reduces the levels of key proteins in MAPK and PI3K signaling pathways in SW620 and HCT116 cells[1].
SOS1-IN-27 (1 μM; 0-60 min) exhibits moderate intrinsic clearance (CLint=36.12 mL/min/kg) and a T1/2 of 48.13 min in human liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:SW620 and HCT116 cells
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Concentration:0.2 μM, 0.4 μM, 0.8 μM
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Incubation Time:14 days
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Result:Reduced the number of colonies in a concentration-dependent manner.
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Cell Line:SW620 and HCT116 cells
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Concentration:2 μM, 4 μM, 8 μM
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Incubation Time:48 h
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Result:Significantly increased the proportion of annexin-V-positive cells in a concentration-dependent manner.
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Cell Line:SW620 and HCT116 cells
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Concentration:2 μM, 4 μM, 8 μM
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Incubation Time:48 h
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Result:Resulted in a concentration-dependent increase in the proportion of cells in the G1 phase.
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Cell Line:SW620 and HCT116 cells
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Concentration:0.5 μM, 1 μM, 2μM
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Incubation Time:72 h
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Result:Reduced cyclin D1 protein levels.
Resulted in a concentration-dependent reduction in the phosphorylation of CRAF, MEK, and ERK in the two cell lines.
Reduced p-AKT protein levels.
Parmacokinetics
In Vivo
SOS1-IN-27 (700 mg/kg; p.o.; single dose) possesses high tolerable doses and favorable safety profiles in Balb/c mice[1].
SOS1-IN-27 (30-60 mg/kg; i.p.; once daily; for 18 days) inhibits tumor growth and demonstrates a good safety profile in HCT116 xenograft models[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Female Balb/c nude mice (6-8 weeks, 20-22 g)[1]
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Dosage:50 mg/kg
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Administration:p.o.; single dose
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Result:Accumulated primarily in the stomach and intestine.
Reached a peak intestinal concentration of 81802 ng/g at 4.0 h.
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Animal Model:Female Balb/c mice (6-8 weeks, 20-25 g)[1]
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Dosage:700 mg/kg
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Administration:p.o.; single dose
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Result:Had no significant effect on the body weight of mice.
Did not alter blood biochemical parameters.
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Animal Model:Female Balb/c nude mice (6-8 weeks, 18-22 g) were subcutaneously inoculated with HCT116 cells (5 × 106 cells per mouse)[1].
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Dosage:30 mg/kg, 60 mg/kg
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Administration:i.p.; once daily; for 18 days
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Result:Dose-dependently suppressed HCT116 xenograft tumor volume, with tumor growth inhibition (TGI) values of 71.6% at 30 mg/kg and 84.2% at 60 mg/kg.
Selectively downregulated intratumoral p-ERK levels without obvious p-ERK suppression in normal stomach, liver and lung tissues of tumor-bearing mice.
Chemical Information
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Molecular Weight 497.72
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Formula C32H43N5
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SMILES
C[C@@H](NC1=NC(N(C)C)=NC2=CC=C(C=C21)N3CCCC3)C4=CC=C(C=C4)C5=CC(C)(CC(C)(C5)C)C
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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.
Protocols
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Apoptosis
Apoptosis, also called programmed cell death, is generally characterized by distinct morphological characteristics.
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TUNEL staining for apoptotic DNA fragmentation
TUNEL staining detects DNA strand breaks by using terminal deoxynucleotidyl transferase to add labeled nucleotides to exposed 3′-OH DNA termini, generating either microscopic staining in fixed cells or tissue sections, or fluorescence/cytometric signal in cell suspensions. TUNEL positivity reflects DNA fragmentation but should not be interpreted alone as definitive apoptosis, because TUNEL can also label necrotic, autolytic, mechanically damaged, or DNA-repair-associated DNA breaks.
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Annexin V plus membrane-impermeant dye apoptosis staining
Annexin V-based apoptosis assays rely on the detection of phosphatidylserine (PS) externalization from the inner leaflet of the plasma membrane to the outer leaflet, an early biochemical hallmark of apoptosis. Fluorescently labeled Annexin V binds PS in a calcium-dependent manner, enabling identification of early apoptotic cells by flow cytometry or fluorescence microscopy. When combined with a membrane-impermeant DNA-binding dye (e. g. , propidium iodide), this approach allows discrimination between viable (Annexin V−/dye−), early apoptotic (Annexin V+/dye−), and late apoptotic or necrotic (Annexin V+/dye+) cell populations by assessing membrane integrity and PS exposure.
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Apoptosis Solutions
Apoptosis is a regulated, generally non-lytic cell-death pathway that removes unwanted, damaged, infected, or abnormal cells through coordinated morphological changes, caspase activation, DNA fragmentation, and membrane remodeling. The intrinsic apoptosis pathway is controlled mainly by mitochondrial outer membrane permeabilization, BCL-2 family proteins, cytochrome c release, apoptosome formation, caspase-9 activation, and downstream executioner caspase-3/7 activation. The extrinsic apoptosis pathway is initiated by death receptors such as Fas, TNFR, and TRAIL receptors, which recruit adaptor proteins and activate caspase-8 before engaging executioner caspases or mitochondrial amplification through BID cleavage. Apoptosis is linked to many phenotypes, including cancer cell killing, tissue homeostasis, immune regulation, neurodegeneration, infection response, and treatment-induced cytotoxicity; unresolved questions include how apoptosis interacts with necroptosis, pyroptosis, ferroptos
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SOS1-IN-27 Related Classifications
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