GIT1-IN-1
GIT1-IN-1 is an inhibitor of ARF GTPase-activating protein 1 (GIT1) with a KD of 6.2 μM. GIT1-IN-1 induces apoptosis (apoptosis) in liver and colon cancer cells, arrests the cell cycle at the G2/M phase, and inhibits cell proliferation, colony formation and migration. GIT1-IN-1 inhibits the activities of MEK and ERK, reduces the expression level of cyclin D1, and stabilizes cyclin B1 protein in liver and colon cancer cells. GIT1-IN-1 can be used in the research of liver cancer and colon cancer.
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- CAS. Nr.: 844464-54-6
- Formel: C21H20N4O4S
- Molecular Weight:424.47
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Speicherung:
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Biologische Aktivität
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ERK1 |
ERK2 |
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MEK2 |
CDK1/cyclinB1 |
GIT1-IN-1 (Compound C3) (10-100 μM; 24 h) inhibits viability and proliferation of HepG2, Hep3B, MzChA-1, HT-29, and RKO liver and colon cancer cells with an IC50 of around 20 μM, but does not affect non-malignant AML12, HEK293, or primary mouse or human hepatocytes at concentrations up to 100 μM[1].
GIT1-IN-1 (1-5 μM; 24 h) induces dose-dependent G2/M phase arrest in HepG2 and RKO liver and colon cancer cells, but does not affect cell cycle progression in non-malignant AML12 or HEK293 cells[1].
GIT1-IN-1 (5 μM; 24-48 h) induces time-dependent apoptosis in RKO colon cancer cells and increases apoptosis and necrosis in HepG2 liver cancer cells after 48 hours, but does not induce cell death in non-malignant AML12, HEK293, or primary mouse or human hepatocytes[1].
GIT1-IN-1 (1-10 μM; 24 h) inhibits clonogenic potential of HepG2 liver cancer cells and RKO colon cancer cells in a dose-dependent manner, but does not affect non-malignant AML12 cells[1].
GIT1-IN-1 (1-2 μM; 24 h) inhibits migration of RKO colon cancer cells and MzChA-1 liver cancer cells in a dose-dependent manner[1].
GIT1-IN-1 (5-10 μM; 24 h) at 10 μM disrupts GIT1-MAT2B and MEK1/2-cRAF/BRAF/ERK1/2/GIT1 interactions, and at 5 μM disrupts GIT1-CDC20, GIT1-APC3, cyclin B1-CDC20, and cyclin B1-APC3 interactions while enhancing GIT1-cyclin B1 interactions in HepG2 and RKO liver and colon cancer cells[1].
GIT1-IN-1 (2-10 μM; 24 h) inhibits MEK and ERK pathway activity, as measured by reduced pMEK1/2, pERK1/2, and cyclin D1 levels, in HepG2, RKO, and MC38 liver and colon cancer cells, but does not affect pathway activity in non-malignant AML12 cells[1].
GIT1-IN-1 (2-5 μM; 24 h) increases cyclin B1 protein stability, cyclin B1-CDK1 complex formation, and CDK1 activity in HepG2 and RKO liver and colon cancer cells, as indicated by a prolonged cyclin B1 half-life, reduced inhibitory CDK1 phosphorylation, and increased activating cyclin B1 phosphorylation[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HepG2, Hep3B, MzChA-1, HT-29, RKO, AML12, HEK293, primary mouse hepatocytes, primary human hepatocytes
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Concentration:10 μM; 50 μM; 100 μM
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Incubation Time:24 h
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Result:Inhibited growth of HepG2, Hep3B, MzChA-1, HT-29, and RKO cells at 10 μM.
Exhibited dose-dependent reduction in viability and proliferation of cancer cells at 10, 50, and 100 μM.
Exerted dose-dependent inhibition of cancer cell viability with an IC50 of around 20 μM.
Did not reduce viability or proliferation in AML12, HEK293, primary mouse hepatocytes, or primary human hepatocytes at concentrations up to 100 μM.
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Cell Line:HepG2, RKO, AML12, HEK293
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Concentration:1 μM; 2 μM; 5 μM
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Incubation Time:24 h
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Result:Reduced the percentage of HepG2 and RKO cells in the G1 phase.
Significantly increased the percentage of HepG2 and RKO cells in the G2/M phase, indicating G2/M phase arrest.
Induced dose-dependent G2/M phase arrest in HepG2 and RKO cells at concentrations from 1 to 5 μM.
Caused no G2/M arrest in AML12 or HEK293 cells.
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Cell Line:HepG2, RKO, AML12, HEK293, primary mouse hepatocytes, primary human hepatocytes
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Concentration:5 μM
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Incubation Time:24 h; 48 h
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Result:Induced significant time-dependent apoptosis in RKO cells.
Increased apoptosis and necrosis significantly in HepG2 cells after 48 hours of treatment, though absolute values remained low.
Caused no increase in apoptosis or necrosis in AML12, HEK293, primary mouse hepatocytes, or primary human hepatocytes after 48 hours of treatment.
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Cell Line:RKO, MzChA-1
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Concentration:1 μM; 2 μM
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Incubation Time:24 h
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Result:Induced dose-dependent inhibition of cell migration in both RKO and MzChA-1 cells at 1 and 2 μM, measured as reduced scratch closure relative to baseline.
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Cell Line:HepG2, RKO
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Concentration:5 μM; 10 μM
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Incubation Time:24 h
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Result:Reduced the interaction between GIT1 and MAT2B in HepG2 cells at 10 μM.
Reduced recruitment of cRAF, BRAF, ERK1/2, and GIT1 to MEK1/2 in HepG2 and RKO cells at 10 μM.
Reduced interactions between GIT1 and CDC20, GIT1 and APC3, cyclin B1 and CDC20, and cyclin B1 and APC3 in HepG2 and RKO cells at 5 μM.
Enhanced the interaction between GIT1 and cyclin B1 in HepG2 cells at 5 μM.
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Cell Line:HepG2, RKO, MC38, AML12
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Concentration:2 μM; 3 μM; 5 μM; 10 μM
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Incubation Time:24 h
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Result:Reduced phosphorylated MEK1/2 (pMEK1/2) levels in HepG2 and RKO cells at 2, 3, and 5 μM.
Reduced phosphorylated ERK1/2 (pERK1/2) and cyclin D1 levels in HepG2 and MC38 cells at 10 μM.
Caused no effect on pMEK1/2, pERK1/2, or cyclin D1 levels in AML12 cells.
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Cell Line:HepG2, RKO, MC38
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Concentration:2 μM; 3 μM; 5 μM
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Incubation Time:24 h; 0, 1, 2, 4, 6 h (with CHX pretreatment)
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Result:Caused dose-dependent increase in cyclin B1 protein levels in HepG2 cells at 2, 3, and 5 μM.
Induced slight increase in cyclin B1 mRNA level (≤ 30%) and significant stabilization of cyclin B1 protein in HepG2 cells, prolonging the half-life of cyclin B1 from 3.6 h to > 24 h.
Increased formation of the cyclin B1-CDK1 complex in HepG2 and RKO cells.
Reduced inhibitory phosphorylation of CDK1 (p-Thr14/p-Tyr15) in HepG2 and MC38 cells.
Increased activating phosphorylation of cyclin B1 (p-S116) in HepG2 cells.
GIT1-IN-1 (25 mg/kg; intraperitoneal; daily; 5 days) significantly inhibits the growth of intrahepatic human colorectal cancer xenografts in nude mice[1].
GIT1-IN-1 (15-20 mg/kg; intraperitoneal; intermittent dosing) significantly inhibits colorectal cancer liver metastasis in immune-competent C57BL/6 mice without causing measurable hepatic toxicity[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (both sexes)[1]
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Dosage:100 μM
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Administration:intratumoral; every other day; 6 days
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Result:Reduced tumor volume significantly compared to DMSO control.
Increased apoptotic cells significantly (TUNEL staining).
Reduced proliferation score significantly (PCNA staining).
Decreased phosphorylated MEK1/2 (Ser218/222) activity significantly relative to total MEK1/2, while GIT1 protein levels remained unchanged.
Changed MC38 tumor cells from spindle-shaped to small round cells (histological analysis).
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Animal Model:Nude (male, 4 months old)[1]
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Dosage:25 mg/kg
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Administration:intraperitoneal; daily; 5 days
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Result:Reduced liver tumor bioluminescent intensity significantly relative to baseline and DMSO control.
Reduced tumor burden compared to DMSO-treated mice (gross liver examination).
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Animal Model:C57BL/6 (both sexes)[1]
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Dosage:20 mg/kg (day 1); 15 mg/kg (daily for 3 days, then daily for 2 days after 2-day rest)
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Administration:intraperitoneal; intermittent dosing (20 mg/kg day 1, then 15 mg/kg daily ×3, 2-day rest, 15 mg/kg daily ×2)
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Result:Reduced bioluminescent intensity significantly relative to DMSO control, indicating inhibited liver tumor growth and metastasis.
Showed no significant difference in plasma ALT and AST levels compared to DMSO control, indicating no overt hepatic toxicity.
Reduced tumor burden compared to DMSO-treated mice (histological analysis).
Chemical Information
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CAS. Nr. 844464-54-6
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Molecular Weight 424.47
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Formel C21H20N4O4S
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SMILES
O=C(CN1C(C(SC2=C3C=C4C(CC(C)(C)OC4)=N2)=C3N=C1)=O)NCC5=CC=CO5
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
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Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
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