- Cart - 0 item(s)
- $0.00
Your shopping cart is empty!
- Chemistry
- Bioactive Molecules
- Anti-infection
- Apoptosis
- Autophagy
- Cell Cycle/DNA Damage
- Cytoskeleton
- Epigenetics
- GPCR/G Protein
- Immunology/Inflammation
- JAK/STAT Signaling
- MAPK/ERK Pathway
- Membrane Transporter/Ion Channel
- Metabolic Enzyme/Protease
- Neuronal Signaling
- NF-κB
- PI3K/Akt/mTOR
- PROTAC
- Protein Tyrosine Kinase/RTK
- Stem Cell/Wnt
- TGF-beta/Smad
- Vitamin D Related/Nuclear Receptor
- Others
- Methylation
- Cytoskeletal Signaling
- Natural Products
- Alkaloids
- Amino acid
- Anthraquinones
- Cerebrosides
- Chalcones
- Coumarins
- Diterpenoids
- Flavonoids
- Iridoids
- Lignans
- Lipids
- Miscellaneous
- Monoterpenoids
- Other terpenes
- Phenols
- Phenylpropanoids
- Quinones
- Saccharides
- Sesquiterpenoids
- Steroids
- Tetraterpenoids
- Thiophenes
- Triterpenoids
- Xanthones
- Polyphenols
- Stibene glucosides
- Oligose
- Anthocyanins
- Miscellaneous
- Chromones
- Terpenoids
- Indoles
- Procyanidins
- Aliphatics
- Botanical Cyclopeptides
- ADCs
- Antibodies
- Multiplex IHC
- Material Science
- Others
[CAS NO. 898044-15-0] PF-3758309
| Ships within | Stock | Price | Qty | Total |
Please click "REQUEST A QUOTE" button if there is no stock, or you need other sizes or custom synthesis.
| Catalog: | HY-13007 |
| Brand: | MCE |
| CAS: | 898044-15-0 |
Overview
| MDL | MFCD18633226 |
|---|---|
| Molecular Weight | 490.62 |
| Molecular Formula | C25H30N8OS |
| SMILES | CC1=NC2=C(SC=C2)C(NC3=NNC4=C3CN(C(N[C@@H](C5=CC=CC=C5)CN(C)C)=O)C4(C)C)=N1 |
5 Publications Citing Use of MCE
Summary
PF-3758309 (PF-03758309) is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 ( K d = 2.7 nM; K i =18.7 nM). PF-3758309 has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis , cytoskeletal remodeling, and inhibition of proliferation [1] [2] [3] .
IC50 & Target
|
PAK4 18.7 nM (Ki) |
PAK1 13.7 nM (Ki) |
PAK5 18.1 nM (Ki) |
PAK6 17.1 nM (Ki) |
PAK2 190 nM (IC 50 ) |
PAK3 99 nM (IC 50 ) |
PAK4 2.7 nM (Kd) |
In Vitro
PF-3758309 has similar enzymatic potency against the kinase domains of the other group B PAKs (PAK5, K
i
=18.1 nM; PAK6, K
i
=17.1 nM) and group A PAK1 (K
i
=13.7 nM), but is less active against the other two group A PAKs (PAK2, IC
50
=190 nM; PAK3, IC
50
=99 nM)
[1]
.
In cells, PF-3758309 inhibits phosphorylation of the PAK4 substrate GEF-H1 (IC
50
=1.3 nM) and anchorage-independent growth of a panel of tumor cell lines (IC
50
=4.7 nM)
[1]
.
PF-3758309 also inhibits endogenous pGEF-H1 accumulation in HCT116 cells. PF-3758309 potently inhibits cellular proliferation (IC
50
=20 nM) and anchorage-independent growth (IC
50
=27 nM) of A549 cells
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
PF-3758309 (7.5-30 mg/kg; p.o.; twice daily for 9-18 days) results in statistically significant tumor growth inhibition (TGI) in HCT116 and A549 models [1] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| Animal Model: | Female nu/nu, CRL breed 6–8 weeks old mice (bearing HCT116 and A549 tumors) [1] |
| Dosage: | 7.5-30 mg/kg |
| Administration: | Oral administration; twice daily for 9-18 days |
| Result: | Significant tumor growth inhibition (TGI) in HCT116 and A549 models. |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT00932126 | Pfizer |
Advanced Solid Tumors
|
September 2009 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
| Powder | -20°C | 3 years |
|---|---|---|
| 4°C | 2 years | |
| In solvent | -80°C | 6 months |
| -20°C | 1 month |
Solvent & Solubility
DMSO : ≥ 100 mg/mL ( 203.82 mM )
* "≥" means soluble, but saturation unknown.
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 |
References
- [1] Murray, Brion W., et al. Small-molecule p21-activated kinase inhibitor PF3758309 is a potent inhibitor of oncogenic signaling and tumor growth. Proceedings of the National Academy of Sciences of the United States of America (2010), 107(20), 9446-9451, S94
- [2] Zhao ZS, et al. Do PAKs make good drug targets? F1000 Biol Rep. 2010 Sep 23;2:70.
- [3] Ryu BJ, et al. PF-3758309, p21-activated kinase 4 inhibitor, suppresses migration and invasion of A549 human lung cancer cells via regulation of CREB, NF-κB, and β-catenin signalings. Mol Cell Biochem. 2014 Apr;389(1-2):69-77.
- [4] Pitts TM, et al. Association of the epithelial-to-mesenchymal transition phenotype with responsiveness to the p21-activated kinase inhibitor, PF-3758309, in colon cancer models. Front Pharmacol. 2013 Mar 28;4:35.
Arctom is a premier supply platform offering over 600K unique items of Building Blocks, Bioactive Molecules, Natural Products, ADC PEG Linkers, Antibodies, and other Research Chemicals for global pharmaceutical, biotech, university, and industrial customers. We accelerate your research by providing better and faster purchasing experience & services.