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  2. PAK

PF-3758309 

Cat. No.: HY-13007 Purity: 98.41%
Handling Instructions

PF-3758309 is an inhbitor of PAK with IC50 of 1.3 nM for PAK4.

For research use only. We do not sell to patients.

PF-3758309 Chemical Structure

PF-3758309 Chemical Structure

CAS No. : 898044-15-0

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 73 In-stock
Estimated Time of Arrival: December 31
5 mg USD 66 In-stock
Estimated Time of Arrival: December 31
10 mg USD 96 In-stock
Estimated Time of Arrival: December 31
50 mg USD 288 In-stock
Estimated Time of Arrival: December 31
100 mg USD 480 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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    PF-3758309 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Kinobead western Blot readout for selected inhibitor:protein combinations.

    PF-3758309 purchased from MCE. Usage Cited in: Science. 2017 Dec 1;358(6367). pii: eaan4368.

    Immunoblot analysis in MV-4-11 cells and MOLM-13, FLT3-WT and FLT3-ITD transfected HEK293 cells, and Ba/F3 FLT3-ITD cells revealed FLT3 target engagement for Golvatinib and Cabozantinib.

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    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    PF-3758309 is an inhbitor of PAK with IC50 of 1.3 nM for PAK4.

    IC50 & Target[1]

    PAK4

    18.7 nM (Ki)

    PAK1

    13.7 nM (Ki)

    PAK5

    18.1 nM (Ki)

    PAK6

    17.1 nM (Ki)

    In Vitro

    F-3758309 binds directly to PAK4 with an in vitro potency of 2.7-4.5 nM. PF-3758309 has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, Ki=18.1±5.1 nM; PAK6, Ki=17.1±5.3 nM) and group A PAK1 (Ki=13.7±1.8 nM), but is less active against the other two group A PAKs (PAK2, IC50=190 nM; PAK3, IC50=99 nM). PAK4 phosphorylates GEF-H1 on a previously characterized serine residue 810 and is inhibited by PF-3758309 (IC50=1.3±0.5 nM). PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells[1]. PF-3758309 is profiled for its growth-inhibitory activity in a panel of 92 tumor cell lines, half of which exhibits IC50 values of less than 10 nM[2]. The proliferation of A549 cells is affected at the treatment with lower dosage (1 μM) of PF-3758309[3].

    In Vivo

    PF-3758309 (7.5-30 mg/kg BID, p.o.) results in statistically significant tumor growth inhibition (TGI) in five models including HCT116 and A549 models. PF-3758309 (15 mg/kg BID, p.o.) is found to inhibit [3H]FLT uptake 32.5% in the HCT116 tumor xenografts by day 6. PF-3758309 treatment shows a significant increase in the apoptotic marker activated caspase 3 in HCT116 tumors[1]. PF-3758309 (25 mg/kg, p.o.) exhibits antiproliferative effects on cell line xenografts[4].

    Solvent & Solubility
    In Vitro: 

    10 mM in DMSO

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.0382 mL 10.1912 mL 20.3824 mL
    5 mM 0.4076 mL 2.0382 mL 4.0765 mL
    10 mM 0.2038 mL 1.0191 mL 2.0382 mL
    *Please refer to the solubility information to select the appropriate solvent.
    References
    Cell Assay
    [3]

    CCK-8 assay is performed to determine cell viability. Cells are seeded at a density of 104 cells per well into 96-well plates with 10 % fetal bovine serum and incubated for 24 h. Then, cells are treated with PF-3758309 at various concentrations (0, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, and 30 μM) for 3 days. After the exposure period, the medium is changed and incubated with CCK-8 solution (10 % of the total volume)/well for 30 min. The medium is measured spectrophotometrically at 450 nm and the percentage of viable cells is estimated by comparison with the 0.3 % DMSO control cells.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [4]

    Five- to six-week-old female athymic nude mice are used. Mice are caged in five groups and kept on a 12-h light/dark cycle and provided with sterilized food and water ad libitum. Animals are allowed to acclimate for at least 7 days before any handling. All CRC cells are harvested in exponential phase growth and resuspended in a 1:1 mixture of serum-free RPMI 1640 and Matrigel. Five to ten million cells per mouse are injected s.c. into the flank using a 23-gage needle. Mice are monitored daily for signs of toxicity and are weighed twice weekly. Tumor size is evaluated twice per week by caliper measurements using the following formula: tumor volume=length×width2×0.52. When tumors reached 150-300 mm3 mice are randomized into two groups with at least 10 tumors per group. Mice are then treated for 14 days with either vehicle control (0.5% methylcellulose), or PF-3758309 (25 mg/kg) twice daily by oral gavage.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References
    Molecular Weight

    490.62

    Formula

    C₂₅H₃₀N₈OS

    CAS No.

    898044-15-0

    SMILES

    CC1=NC2=C(SC=C2)C(NC3=NNC4=C3CN(C(N[[email protected]@H](C5=CC=CC=C5)CN(C)C)=O)C4(C)C)=N1

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Shipping

    Room temperature in continental US; may vary elsewhere

    Purity: 98.41%

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    Product Name:
    PF-3758309
    Cat. No.:
    HY-13007
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    PF-3758309

    Cat. No.: HY-13007