Home Cytoskeletal Signaling PAK inhibitor - Apoptosis related activator PF-3758309 For research use only.

PF-3758309

Synonyms: PF-03758309

PF-03758309 (PF-03758309) is a potent, ATP-competitive, pyrrolopyrazole inhibitor of PAK4 with Kd of 2.7 nM. PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model.

PF-3758309 Chemical Structure

PF-3758309 Chemical Structure

CAS No. 898044-15-0

Purity & Quality Control

PF-3758309 Related Products

Signaling Pathway

PAK Signaling Pathways

PAK Signaling Pathway

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
human MDA-MB-436 cells Cytotoxic assay 24-48 h Cytotoxicity against human MDA-MB-436 cells assessed as reduction in cell viability after 24 to 48 hrs by Celltiter-glo luminescence assay, IC50=0.79 nM 24432870
HCT116 Antiproliferative activity against 72 hrs Antiproliferative activity against human HCT116 cells after 72 hrs by CCK8 assay, IC50=0.039μM. 29886323
A549 Antiproliferative activity against 72 hrs Antiproliferative activity against human A549 cells after 72 hrs by CCK8 assay, IC50=0.463μM. 29886323
TC32 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
U-2 OS qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells 29435139
Saos-2 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells 29435139
SK-N-SH qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
BT-12 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells 29435139
Rh18 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
OHS-50 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells 29435139
RD qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
MG 63 (6-TG R) qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells 29435139
fibroblast cells qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells 29435139
Rh41 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells) 29435139
BT-12 qHTS of pediatric cancer cell lines to identify multiple opportunities for qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-12 cells 29435139
Click to View More Cell Line Experimental Data

Biological Activity

Description PF-03758309 (PF-03758309) is a potent, ATP-competitive, pyrrolopyrazole inhibitor of PAK4 with Kd of 2.7 nM. PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model.
Features PF-3758309 is potent toward a broad array of tumor cell lines from different tumor types.
Targets
PAK1 [1]
(Cell-free assay)		 PAK6 [1]
(Cell-free assay)		 PAK5 [1]
(Cell-free assay)		 PAK4 [1]
(Cell-free assay)		 PAK3 [1]
(Cell-free assay)		 Click to View More Targets
13.7 nM(Ki) 17.1 nM(Ki) 18.1 nM(Ki) 18.7 nM(Ki) 99 nM
In vitro
In vitro

PF-3758309 is a potent (Kd = 2.7 nM), ATP-competitive inhibitor of PAK4 with Ki of 18.7 nM. In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC50 = 1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC50 = 4.7 nM). PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC50 = 20 nM) and anchorage-independent growth (IC50 = 27 nM) of A549 cells. [1]
Kinase Assay Phospho-GEF-H1 Cellular Assay
TR-293-KDG cells are constructed from HEK293 cells stably transfected with tetracycline-inducible PAK4-kinase domain (amino acids 291-591) and constitutively expressed HA-tagged GEFH1ΔDH (amino acids 210-921). TR-293-KDG cells are incubated for 3 h with PF-3758309, captured on an anti-HA antibody-coated plate, detected with an anti-phospho-S810-GEF-H1 antibody, and quantified with a horseradish peroxidase-goat anti-rabbit antibody conjugate.
Cell Research Cell lines HEK293T, HCT116, and SKOV3 cells
Concentrations ~1 μM
Incubation Time 72 hours
Method

A panel of cancer cell lines is used to test the potency of PF-3758309. On day 1, cells are plated on 384-well plates. Onday2, compounds are added to the cell culture. The cells are incubated with the compound for 3 days. On day 5, all media are aspirated from the wells. Dose-dependent effects of PF-3758309 on cell proliferation are quantified via the CellTiter-Glo Luminescent Cell Viability Assay(a,b,c), which is a homogeneous method of determining the number of viable cells in culture based on quantitation of the ATP present, an indicator of metabolically active cells. Proliferation data displayed for HEK293T, HCT116, and SKOV3 cells are measured using the Cyquant NF assay as specified by the manufacturer. Results for each drug are normalized to vehicle control and expressed as a percentage of maximum assay inhibition relative to Bleomycin. Error bars represent the SD from at least three experiments.
Experimental Result Images Methods Biomarkers Images PMID
Western blot PAK4 / PI3K / p-AKT / AKT / p-mTOR / mTOR 28407679
In Vivo
In vivo

PF-3758309 blocks the growth of multiple human tumor xenografts, with a plasma EC50 value of 0.4 nM in the most sensitive model. PF-3758309 is antiproliferative and induces apoptosis in a HCT116 tumor model. [1]
Animal Research Animal Models Xenograft tumors in nude mice
Dosages 7.5-30 mg/kg BID
Administration p.o.

Chemical Information & Solubility

Molecular Weight 490.62 Formula

C25H30N8OS
CAS No. 898044-15-0 SDF Download PF-3758309 SDF
Smiles CC1=NC2=C(C(=N1)NC3=NNC4=C3CN(C4(C)C)C(=O)NC(CN(C)C)C5=CC=CC=C5)SC=C2
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 98 mg/mL ( (199.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 98 mg/mL

Water : Insoluble


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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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Frequently Asked Questions

Question 1:
If this compound crosses the blood brain barrier?

Answer:
We're sorry we don't have any data on whether S7094 can cross BBB or not, the following reference indicate that it can not: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490962/.

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