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PF-3758309 PAK inhibitor

Name: PF-3758309
Brand: Selleck Chemicals
SKU: S7094
Availability: InStock
Rating: 5 (29 reviews)

Cat.No.S7094

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

Chemical Structure

Molecular Weight: 490.62

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.98%

99.98

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Cell Culture, Treatment & Working Concentration

Cell Lines	Assay Type	Incubation Time	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

Chemical Information, Storage & Stability

Molecular Weight	490.62	Formula	C₂₅H₃₀N₈OS	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	898044-15-0	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	PF-03758309			Smiles	CC1=NC2=C(C(=N1)NC3=NNC4=C3CN(C4(C)C)C(=O)NC(CN(C)C)C5=CC=CC=C5)SC=C2

Solubility

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

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (10.19mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	5.000mg/ml (10.19mM)	Taking the 1 mL working solution as an example, add 50 μL of 100 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Features	PF-3758309 is potent toward a broad array of tumor cell lines from different tumor types.
Targets/IC₅₀/Ki	PAK1 ^[1] (Cell-free assay) 13.7 nM(Ki) PAK6 ^[1] (Cell-free assay) 17.1 nM(Ki) PAK5 ^[1] (Cell-free assay) 18.1 nM(Ki) PAK4 ^[1] (Cell-free assay) 18.7 nM(Ki) PAK3 ^[1] (Cell-free assay) 99 nM PAK2 ^[1] (Cell-free assay) 190 nM
In vitro	PF-3758309 is a potent (K_d = 2.7 nM), ATP-competitive inhibitor of PAK4 with K_i of 18.7 nM. In cells, this compound 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). It also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. This chemical 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
Kinase 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.
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. This compound is antiproliferative and induces apoptosis in a HCT116 tumor model. ^[1]
References	https://pubmed.ncbi.nlm.nih.gov/20439741/

Applications

Methods	Biomarkers	Images	PMID
Western blot	PAK4 / PI3K / p-AKT / AKT / p-mTOR / mTOR		28407679

Tech Support

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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 it can cross BBB or not, the following reference indicate that this compound can not: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490962/.

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