PAK4-IN-8
PAK4-IN-8 is an orally active and selective PAK4 inhibitor (IC50 = 8.32 nM) that exhibits antiproliferative activity against TNBC cells. PAK4-IN-8 inhibits PAK4 kinase activity and its downstream LIMK1‑Cofilin and AKT signaling axes, and downregulates c‑Src phosphorylation. PAK4-IN-8 induces cell cycle arrest, apoptosis, and elevated intracellular ROS, while inhibiting TNBC cell migration and invasion. PAK4-IN-8 inhibits tumor growth in an orthotopic xenograft tumor model, and when combined with Gefitinib (HY-50895) achieves synergistic inhibition and reduces lung metastasis. PAK4-IN-8 can be used for research on triple-negative breast cancer.
For research use only. We do not sell to patients.
- Formula: C28H26N6
- Molecular Weight:446.55
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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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Biological Activity
Description
IC50 & Target
[1]|
PAK4 8.32 nM (IC50) |
EGFR |
LIMK1 |
Akt |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MDA-MB-231 | IC50 |
1.15 μM
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Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 48 hrs by MTT assay.
Antiproliferative activity against human MDA-MB-231 cells assessed as viability reduction incubated 48 hrs by MTT assay.
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42800115 |
| BT-549 | IC50 |
1.28 μM
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Antiproliferative activity against human BT-549 cells assessed as viability reduction incubated 48 hrs by MTT assay.
Antiproliferative activity against human BT-549 cells assessed as viability reduction incubated 48 hrs by MTT assay.
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42800115 |
| HCC1806 | IC50 |
1.51 μM
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Antiproliferative activity against human HCC-1806 cells assessed as viability reduction incubated 48 hrs by MTT assay.
Antiproliferative activity against human HCC-1806 cells assessed as viability reduction incubated 48 hrs by MTT assay.
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42800115 |
| A549 | IC50 |
2.53 μM
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Antiproliferative activity against human A549 cells assessed as viability reduction incubated 48 hrs by MTT assay.
Antiproliferative activity against human A549 cells assessed as viability reduction incubated 48 hrs by MTT assay.
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42800115 |
In Vitro
PAK4-IN-8 (0.3-4.8 µM; 24-48 h) inhibits MDA-MB-231 migration and invasion in a concentration-dependent manner[1].
PAK4-IN-8 (0.4 µM; 48 h) sensitizes MDA-MB-231, BT-549, and HCC-1806 TNBC cells to Gefitinib (HY-50895), and the combination decreases the IC50 in MDA-MB-231 from 1.2 µM to 0.8 µM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MDA-MB-231 cells
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Concentration:0.3, 0.6, 1.2, 2.4, 4.8 µM (Wound healing)
0.3, 0.6, 1.2, 2.4, 4.8 µM (Transwell) -
Incubation Time:24 and 48 h (Wound healing)
24 h (Transwell) -
Result:Suppressed MDA‑MB‑231 migration in a concentration‑dependent fashion.
Reduced wound closure by approximately 35 % at 24 h and 45 % at 48 h under 1.2 µM treatment.
Achieved near‑complete migration inhibition at 4.8 µM.
Markedly lowered the count of invading membrane‑traversing cells in Transwell assays and produced near‑complete inhibitory effects at 4.8 µM.
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Cell Line:MDA-MB-231 cells
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Concentration:0.3, 0.6, 1.2, 2.4, 4.8 µM
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Incubation Time:24 h
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Result:Inhibited PAK4 and downstream LIMK1/Cofilin, AKT, c-Src/EGFR, and MAPK signaling while up-regulating p53 and caspase-3 activation in MDA-MB-231 cells.
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Cell Line:MDA-MB-231 cells
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Concentration:0.6, 1.2, 2.4 µM (alone)
0.4, 0.8, 1.6 µM (with 1.3 µM Gefitinib) -
Incubation Time:24 h
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Result:Induced G0/G1 cell cycle arrest in MDA-MB-231 cells, and the effect is enhanced in combination with Gefitinib.
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Cell Line:MDA-MB-231 cells
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Concentration:0.6, 1.2, 2.4 µM (alone)
0.4, 0.8, 1.6 µM (with 1.3 µM Gefitinib) -
Incubation Time:24 h
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Result:Induced dose-dependent apoptosis in MDA-MB-231 cells, with enhanced apoptosis in combination with Gefitinib.
In Vivo
PAK4-IN-8 (15 mg/kg/d; p.o.; once every other day; 21 days) combined with Gefitinib produces 60.39% TGI, and no lung metastasis 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:BALB/c nude (female, 5 weeks old, 18-20 g, 1 × 108 MDA-MB-231 cells suspended in 100 μL of PBS)[1]
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Dosage:25, 50 mg/kg/d (single agent)
15 mg/kg/d (combination with Gefitinib 10 mg/kg/d) -
Administration:p.o.; every other day; 21 days
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Result:Yielded 33.70 % TGI at 25 mg/kg/d and 53.17 % TGI at 50 mg/kg/d.
Attained 60.39 % TGI when dosed at 15 mg/kg/d in combination with Gefitinib 10 mg/kg/d.
Detected no lung metastasis or inflammation in either single‑agent groups or the Gefitinib‑combination group.
Showed extensive necrosis and cellular degeneration within H&E‑stained tumor sections for the 50 mg/kg/d and combination groups, with more severe pathological alterations relative to the 25 mg/kg‑d cohort.
- Cell migration
- Breast Cancer Modeling
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Flow cytometric DNA-content cell-cycle staining
- Zigmond Chamber Chemotaxis Assay
- Under-Agarose Cell Migration Assay
- Transwell/Boyden Chamber Migration Assay
- Apoptosis Solutions
- 3D Collagen/Hydrogel Matrix Migration Assay
- Cell invasion
- Cell-Exclusion Zone Migration Assay
- Dunn/Insall Chamber Chemotaxis Assay
- Western Blot
- Scratch/Wound-Healing Migration Assay
- Annexin V plus membrane-impermeant dye apoptosis staining
- BrdU Incorporation Assay
- ROS/oxidative-stress fluorescent staining
- Neural Crest/Neuronal Cell Migration Explant Assay
- Patient-Derived Orthotopic Xenograft (PDOX)
- Protocol for Cell Cycle
- Cell Viability Determination by MTT Colorimetric Assay
- Kinase activity and phosphorylation assays
- Patient-Derived Xenograft (PDX)
- Tail-Vein Experimental Metastasis Xenograft
- Splenic/Portal-Vein Liver Metastasis Xenograft
- Protocol for Kinase activity and phosphorylation assays
- Subcutaneous Cell-Line-Derived Xenograft
- Orthotopic Cell-Line Xenograft
- Intraperitoneal/Peritoneal Dissemination Xenograft
Chemical Information
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Molecular Weight 446.55
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Formula C28H26N6
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SMILES
CN(CC1)CCN1C2=CC=CC(NC3=NC=NC(C3=C4)=CC=C4C(C=N5)=CC6=C5C=CC=C6)=C2
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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)
PAK4-IN-8 Related Classifications
HY-190490 Related Classifications
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