PAK1
PAK1 is a p21-activated serine/threonine kinase that links Rac/Cdc42 signaling to cell motility, survival, proliferation, cytoskeletal organization, transcription, and translation[1]. Mechanistically, PAK family kinases act as downstream effectors of Rho GTPases, with vertebrate PAKs supporting cytoskeletal remodeling, focal adhesion assembly, cell migration, and synaptic plasticity[2]. In cancer models, PAK1 functions as a signaling node downstream of HGF/MET in pancreatic adenocarcinoma, where PAK1 inhibition blocks cytoskeletal effector signaling, tumor cell motility, tumor growth, and metastasis[3]. In colorectal cancer, Group I Pak inhibition impedes adenoma-to-carcinoma transition by reducing β-catenin activity and suppressing an epithelial-mesenchymal transition program[4]. In neurological disease models, PAK1 knockdown reduces ATXN1 levels in mammalian cells, and pharmacological PAK inhibition decreases ATXN1 levels in an SCA1 mouse model[5]. Compared with related isoforms, PAK1 belongs to Group I PAKs, and inhibitor development must address whether to target one isoform or multiple PAK isoforms[1][5]. For experimental applications, ATP-competitive inhibitors, allosteric inhibitors, and peptide inhibitors provide laboratory tools for studying PAK1 biology and disease contexts[6].
References:
- [1]. Kichina JV, et al. PAK1 as a therapeutic target. Expert Opin Ther Targets. 2010 Jul;14(7):703-25. [Content Brief]
- [2]. Field J, et al. The PAKs come of age: Celebrating 18 years of discovery. Cell Logist. 2012 Apr 1;2(2):54-58. [Content Brief]
- [3]. Zhou W, et al. PAK1 mediates pancreatic cancer cell migration and resistance to MET inhibition. J Pathol. 2014 Dec;234(4):502-13. [Content Brief]
- [4]. Chow HY, et al. Group I Paks are essential for epithelial- mesenchymal transition in an Apc-driven model of colorectal cancer. Nat Commun. 2018 Aug 27;9(1):3473. [Content Brief]
- [5]. Bondar VV, et al. PAK1 regulates ATXN1 levels providing an opportunity to modify its toxicity in spinocerebellar ataxia type 1. Hum Mol Genet. 2018 Aug 15;27(16):2863-2873. [Content Brief]
- [6]. Semenova G, et al. Targeting PAK1. Biochem Soc Trans. 2017 Feb 8;45(1):79-88. [Content Brief]
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PAK1 Related Products (30)
Related Products (30)
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Recombinant Proteins (1)
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PF-3758309 dihydrochloride
0 ImagesCat. No.: HY-13007BSynonyms: PF-03758309 dihydrochloridePF-3758309 (PF-03758309) dihydrochloride is a potent, orally available, and reversible ATP-competitive inhibitor of PAK4 (Kd= 2.7 nM; Ki=18.7 nM). PF-3758309 dihydrochloride has the expected cellular functions of a PAK4 inhibitor: inhibition of anchorage-independent growth, induction of apoptosis, cytoskeletal remodeling, and inhibition of proliferation.
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G-9791
0 ImagesCat. No.: HY-116917CAS No.: 1926204-95-6G-9791, a poyridone side chain analogue, is a potent PAK inhibitor with Ki values of 0.95 nM and 2.0 nM for PAK1 and PAK2, respectively.
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AZ13711265
0 ImagesCat. No.: HY-119216CAS No.: 2016806-55-4AZ13711265 is an orally active PAK1 inhibitor with high selectivity. AZ13711265 has IC50 values of 0.58 nM and 0.11 µM for PAK1 and pPAK1, respectively. AZ13711265 has low lipophilicity and low clearance, and can be used as an in vivo probe compound for PAK1. AZ13711265 can be used in the study of cancer.
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Mesalamine impurity P
0 ImagesCat. No.: HY-131265CAS No.: 887256-40-8Mesalamine impurity P is an impurity of Mesalamine (HY-15027). 5-Aminosalicylic acid (Mesalamine) acts as a specific PPARγ agonist and also inhibits p21-activated kinase 1 (PAK1) and NF-κB.
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YDH-704
0 ImagesCat. No.: HY-187370YDH-704 is a PAK1/HDAC10 inhibitor, with IC50 values of 0.05 μM and 0.02 μM against human targets, respectively. YDH-704 blocks PAK1-mediated oncogenic signaling pathways, inhibits the proliferation and migration of tumor cells, suppresses the epigenetic regulatory function of HDAC10, downregulates PD-L1 expression, and regulates polyamine metabolism. YDH-704 reduces MDSC/Treg infiltration, enhances the infiltration and activation of CD8+ T cells, and inhibits tumor growth and lung metastasis. YDH-704 can be used for research on triple-negative breast cancer.
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ZINC194100678
0 ImagesCat. No.: HY-146783CAS No.: 1995025-05-2ZINC194100678 is a potent PAK1 inhibitor with an IC50 value of 8.37 μM. ZINC194100678 can inhibit MDA-MB-231 cell proliferation. ZINC194100678 can be used for researching anticancer.
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ZMF-10
0 ImagesCat. No.: HY-146786CAS No.: 2415295-37-1
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AK963/40708899
0 ImagesCat. No.: HY-164374CAS No.: 445007-59-0AK963/40708899 is a potent PAK1 inhibitor. AK963/40708899 suppresses the proliferation of human gastric cancer cells by downregulation of PAK1-NF-κB-cyclinB1 pathway. AK963/40708899 induces cell cycle arrest at G2 phase and reduces the migration and invasion. AK963/40708899 inhibits the formation of filopodia and promots cell adhesion which in turn inhibits invasive potential of gastric cells by negatively regulating PAK1-LIMKl-cofilin and PAK1-ERK-FAK pathways.
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