SAIT-PDZ-5179
SAIT-PDZ-5179 is a small-molecule inhibitor of GIPC1 that directly binds to the PDZ domain of GIPC1 with a KD of 943 nM. SAIT-PDZ-5179 reduces the levels of GIPC1-associated signaling proteins and cell viability in pancreatic ductal adenocarcinoma models. SAIT-PDZ-5179 is used for studies on the GIPC1 signaling pathway and pancreatic ductal adenocarcinoma.
For research use only. We do not sell to patients.
- Formula: C30H22FN3O4
- Molecular Weight:507.51
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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]|
GIPC1 943 nM (Kd) |
In Vitro
SAIT-PDZ-5179 (GIPCi) (GIPC1:GIPCi = 1:10; 2 h; 37 °C) interacts with the GIPC1 PDZ domain and induces local conformational stabilization in HDX-MS experiments, and the assay localizes the ligand-associated regions to include the 187-197 region and the adjacent regions of R279, D280, E282, and L283[1].
SAIT-PDZ-5179 (GIPCi 7 μM; GIPC1 PDZ domain 76.4 μM; 25 °C; 90 s equilibration) binds to the GIPC1 PDZ domain in ITC experiments, with a KD of 943 nM and a fitted stoichiometry N close to 1[1].
SAIT-PDZ-5179 (10-50 μM; 72 h) reduces the protein levels of GIPC1, EGFR1, IGF1Rβ and SDC4 in KPC and PANC-1 cells in a concentration-dependent manner[1].
SAIT-PDZ-5179 (10-50 μM; 72 h) reduces the viability of KPC, PANC-1, AsPC-1, and PANC-02 cells in a dose-dependent manner[1].
SAIT-PDZ-5179 (5-50 μM; 72 h) reduces the viability of PDX-6741 and PDX-7114 pancreatic cancer cells in a dose-dependent manner[1].
SAIT-PDZ-5179 (30 μM; followed by 21 days of colony growth) significantly reduces the clonogenic survival of PDX-6741 and PDX-7114 cells[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:KPC; PANC-1
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Concentration:10-50 μM
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Incubation Time:72 h
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Result:Decreased GIPC1 protein expression in a concentration-dependent manner.
Decreased EGFR1 expression.
Decreased IGF1Rβ expression.
Decreased SDC4 expression.
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Cell Line:KPC; PANC-1; AsPC-1; PANC-02
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Concentration:10-50 μM
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Incubation Time:72 h
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Result:Reduced cell viability in a dose-dependent manner across all tested cell lines.
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Cell Line:PDX-6741; PDX-7114
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Concentration:5-50 μM
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Incubation Time:72 h
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Result:Reduced cell viability in a dose-dependent manner in both cell lines.
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Cell Line:PDX-6741; PDX-7114
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Concentration:30 μM
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Incubation Time:Colony growth: 21 days
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Result:Markedly reduced clonogenic survival in both cell lines.
Parmacokinetics
| Species | Dose | Route | Cmax | Tmax | T1/2 | AUCINF_obs | Vz | MRTINF_obs | Vss_obs |
|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 755.4 ng/mL | 0.033 h | 7.71 h | 3173.98 ng·h/mL | 7011.4 mL/kg | 9.63 h | 6069.5 mL/kg |
In Vivo
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly; for 3 consecutive weeks) reduces tumor volume and weight in the KPC orthotopic model, and extends median survival from 28 days in the control group to 43 days[1].
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly; for 3 consecutive weeks) reduces tumor volume and weight and extends median survival from 32 days to 48 days in a PANC-1 orthotopic xenograft model[1].
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly; for 3 consecutive weeks) reduces endpoint tumor volume and tumor weight in the PANC-1 subcutaneous xenograft model[1].
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly; for 3 consecutive weeks) reduces tumor volume and tumor weight in the PDX-6741 orthotopic pancreatic tumor model[1].
Combined intraperitoneal administration of SAIT-PDZ-5179 (10 mg/kg) and GEM (2 mg/kg), given twice weekly for 3 consecutive weeks, produces 78% tumor volume inhibition and 74% tumor weight inhibition in the KPC orthotopic model. These values exceed the Bliss-predicted inhibitions of 71.2% and 69.6%, corresponding to synergistic increases of 6.8% and 4.4%, respectively; the median survival of the combination treatment group is 46 days[1].
Combined intraperitoneal administration of SAIT-PDZ-5179 (10 mg/kg) and GEM (2 mg/kg), given twice weekly for 3 consecutive weeks, produces 61% tumor volume inhibition and 84% tumor weight inhibition in the PANC-1 orthotopic xenograft model. These values are higher than the Bliss-predicted values of 59% and 58.18%, corresponding to synergistic increments of 2% and 25.82%, respectively; the median survival time of the combination treatment group is 54 days[1].
Combined intraperitoneal administration of SAIT-PDZ-5179 (10 mg/kg) and GEM (2 mg/kg), given twice weekly for 3 consecutive weeks, produces 84% tumor volume inhibition and 79% tumor weight inhibition in the PDX-6741 orthotopic model. These values are higher than the Bliss-predicted inhibitions of 66.4% and 70.4%, corresponding to synergistic increments of 17.6% and 8.6%, respectively[1].
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly; for 3 consecutive weeks) increases the infiltration of CD8+ and CD4+ T cells in KPC orthotopic tumors[1].
SAIT-PDZ-5179 (10 mg/kg; i.p.; twice weekly for 3 consecutive weeks) does not induce histological abnormalities in the heart, kidney, liver, lung, or spleen, causes no significant body weight changes, and leads to no obvious alterations in serum ALT, AST, and KIM-1 levels in healthy SCID mice[1].
SAIT-PDZ-5179 (5-25 mg/kg; single slow intravenous bolus injection; 14-day observation period) does not cause mortality in Sprague-Dawley rats at doses of 5-15 mg/kg, whereas 25 mg/kg results in acute death in 4 out of 6 animals after administration; surviving animals at 25 mg/kg exhibit transient somnolence and abdominal breathing, and recover on day 3[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID mice (female, 6-8 weeks old)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly for 3 weeks
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Result:Reduced tumor volume.
Reduced tumor weight.
Prolonged median survival from 32 to 48 days.
Reduced Ki-67 and survivin staining.
Reduced EGFR1, integrin, and IGF1Rβ protein levels in tumor lysates.
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Animal Model:C57BL/6 mice (female, 6-8 weeks old, syngeneic orthotopic pancreatic ductal adenocarcinoma KPC model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; 3 weeks
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Result:Reduced tumor volume.
Reduced tumor weight.
Prolonged median survival from 28 days in controls to 43 days.
Reduced tumor cellularity.
Reduced Ki-67 and survivin staining.
Increased intratumoral CD8+ T-cell infiltration.
Increased intratumoral CD4+ T-cell infiltration.
Reduced EGFR1, integrin, and IGF1Rβ protein levels in tumor lysates.
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Animal Model:SCID mice (female, 6-8 weeks old, subcutaneous PANC-1 pancreatic ductal adenocarcinoma xenograft model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; 3 weeks
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Result:Significantly reduced tumor volume and tumor weight relative to control group animals, and mice exhibited no body weight loss.
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Animal Model:SCID mice (female, 6-8 weeks old, orthotopic PDX-6741 patient-derived pancreatic ductal adenocarcinoma model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; 3 weeks
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Result:Produced marked reduction in tumor burden, with significant decreases in measured tumor volume and tumor weight corresponding to 66.4% tumor volume inhibition and 70.4% tumor weight inhibition relative to control.
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Animal Model:SCID mice (female, 6-8 weeks old, non-tumor bearing)[1]
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Dosage:10 mg/kg
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Administration:i.p.; twice weekly; 3 weeks
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Result:Showed no histopathological signs of toxicity in collected heart, kidney, liver, lung, and spleen tissues, no significant body weight variations were detected across the treatment period, and no elevations in serum ALT, AST, or KIM-1 biomarker levels were observed.
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Animal Model:7-8-week-old rats (Sprague-Dawley, male/female)[1]
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Dosage:5, 10, 15, 25 mg/kg
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Administration:Single slow-bolus intravenous injection; 2 mL/kg; ≤1 mL/min; 14-day observation
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Result:Caused no mortality at 5, 10, or 15 mg/kg.
Caused acute mortality in 4 of 6 animals at 25 mg/kg.
Produced transient lethargy and abdominal breathing in surviving 25 mg/kg animals through day 2, with recovery by day 3.
Produced no compound-related hematological, coagulation, or serum biochemical alterations in surviving animals.
Produced no macroscopic lesions attributable to the compound.
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Animal Model:6–8-week-old mice (C57BL/6, female)[1]
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Dosage:2, 5, 10 mg/kg
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Administration:i.p.;twice weekly for 3 weeks
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Result:Reduced tumor volume in a dose-dependent manner.
Reduced terminal tumor weight in a dose-dependent manner.
Chemical Information
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Molecular Weight 507.51
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Formula C30H22FN3O4
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SMILES
OC1=C2C=CC=CC2=NC3=C1C=CC=C3/C(C4=CC=CC=C4)=C/C(NC5=CC(NC(OC)=O)=C(C=C5)F)=O
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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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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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Mammalian live/dead viability and cytotoxicity staining
Live/dead viability and cytotoxicity staining assays are based on the simultaneous detection of intracellular esterase activity in metabolically active (viable) cells and membrane integrity loss in non-viable cells. In commonly used dual-staining approaches, membrane-permeant fluorogenic substrates are converted by intracellular esterases into fluorescent products in live cells, while impermeant DNA-binding dyes selectively enter cells with compromised plasma membranes and label nucleic acids in dead or dying cells, enabling discrimination between viable and non-viable populations by fluorescence microscopy or flow cytometry.
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CCK-8/WST-8 Cell Proliferation Assay
The CCK-8/WST-8 assay is based on the reduction of the water-soluble tetrazolium salt WST-8 to a water-soluble formazan product by cellular dehydrogenases in metabolically active cells, where the generated formazan amount is proportional to the number of living cells and is quantified by measuring absorbance in the visible range, providing a colorimetric readout for cell viability and proliferation assessment. This class of tetrazolium-based assays improves upon earlier MTT-based systems by producing a water-soluble formazan, eliminating the need for organic solubilization steps and enabling direct spectrophotometric measurement in culture medium.
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MTT Cell Proliferation Assay
The MTT assay is a colorimetric endpoint assay for estimating viable cell number, cell growth, cytotoxicity, or cell activation in cultured mammalian cells. Living cells reduce the yellow tetrazolium salt MTT into purple/blue formazan, while dead cells do not generate the same signal; the resulting color can be quantified with a multiwell spectrophotometer. MTT reduction is commonly interpreted as a readout of metabolic activity that often correlates with viable cell number, but it should not be treated as a direct cell-counting method unless the assay is optimized for the cell type and experimental condition. Studies show that MTT reduction can involve mitochondrial and non-mitochondrial reducing systems, and formazan may accumulate in intracellular lipid droplets rather than simply marking mitochondria.
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Cell Viability Determination by MTT Colorimetric Assay
The following protocol uses the MTT colorimetric assay as a classic literature-established method for assessing cell viability/metabolic activity in cultured mammalian cells. MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] is reduced by metabolically active cells to a colored formazan product; the amount of formazan is quantified spectrophotometrically and provides an indirect measure of metabolically active viable cells. Importantly, MTT reduction reflects cellular oxidoreductase/metabolic activity rather than an absolute direct count of living cells, so changes in cellular metabolism can alter the signal independently of cell number.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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