PF-03758309 PAK4 inhibitor
- Known as:
- PF-03758309 PAK4 suppressor
- Catalog number:
- a-1091
- Product Quantity:
- USD
- Category:
- -
- Supplier:
- ActivBio Active Biochem
- Gene target:
- PF-03758309 PAK4 inhibitor
Related genes to: PF-03758309 PAK4 inhibitor
- Gene:
- PAK4 NIH gene
- Name:
- p21 (RAC1) activated kinase 4
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-07-12
- Date modifiied:
- 2016-05-03
Related products to: PF-03758309 PAK4 inhibitor
Related articles to: PF-03758309 PAK4 inhibitor
- Newborn neurons in the adult hippocampal dentate gyrus (DG) are hyperexcitable, competitive cells involved in behavioral responses to stress and antidepressants. The role and the mechanisms underlying the competitiveness of the newborn neurons in moderating behavioral responses to stress have not yet been comprehensively investigated. Using FosTRAP2 transgenic mice in the learned helplessness (LH) paradigm, we report that voluntary running, a guideline-supported intervention for depression, induces neurogenesis, and that the newly generated neurons compete with LH-TRAPed neurons, thereby reducing stress-induced helpless behavior. Mechanistically, we found that increasing neurogenesis is sufficient to reduce spine density in LH-TRAPed neurons via p21-activated kinase 4 (Pak4) and to attenuate Ca activity in these neurons. Taken together, our findings suggest that highly excitable newborn neurons compete with LH-TRAPed neurons, attenuating helpless behaviors and providing therapeutic value for depressed individuals, who typically show enhanced memory for negative events. - Source: PubMed
Publication date: 2026/08/20
Zhang Can-YuanWei Su-FenWang Ya-PingNie Jia-QiWang QiWu Fu-LingHuang Ming-FengCai Wei-ZhongChen Liang-YuLiu Jin-MingGuo FangLin Xiao-ShanLi Shu-JiGuo Xiang-NaRen Si-QiangCao Xiong - How epithelial tissues remodel while preserving their barrier remains a fundamental question in epithelial biology. In this issue, Adhikary et al. (https://doi.org/10.1083/jcb.202510024) identify PAK4 as a dynamic regulator of vertex remodeling that fine-tunes actomyosin contractility to maintain tissue integrity. - Source: PubMed
Publication date: 2026/08/17
Thiagarajan RaghavanSedzinski Jakub - Environmental chemicals may suppress sperm motility (SM), hyperactivation, and capacitation, thus contributing to male infertility. This investigation was designed to examine the impacts of thiram on human SM and capacitation. - Source: PubMed
Publication date: 2026/06/27
Wen ZinaQiu QinghongDuan LiLiu GangWang YiyanTian ErpoGe Ren-Shan - p21-activated kinase 4 (PAK4), a Group II PAK family member, is a therapeutically relevant candidate target in cancer, metabolic disease, and tissue injury. However, translation of PAK4 biology into drug candidates has been constrained by the conserved ATP-binding architecture of PAK isoforms, unfavorable pharmacokinetic profiles, and suboptimal clinical efficacy. We summarize the evolution of ATP-competitive Type I inhibitors, Type I½ back-pocket inhibitors, allosteric modulators, and PROTAC degraders, and compare representative compounds using potency, isoform selectivity, cellular activity, oral bioavailability, and development status. Particular emphasis is placed on structural determinants of selectivity, including the αC-helix-dependent hydrophobic back pocket, the inward Asp444/Asp458 floor pocket arrangement, and peripheral microenvironment differences that distinguish PAK4 from Group I PAKs. We also summarize the potential ADMET liabilities-such as pronounced efflux, metabolic instability, and poor oral bioavailability-that may arise from structural modifications aimed at enhancing PAK4 selectivity, and discuss rational optimization strategies to navigate these inherent barriers. Finally, we discuss clinical lessons from PF-3758309 and KPT-9274/padnarsertib and highlight how allosteric inhibitors and PROTAC degraders may help address limitations of conventional ATP-site inhibitors. - Source: PubMed
Publication date: 2026/07/31
Shi RuiqingFeng XueWang ZixuanXing YongshuaiYan XianjunXing RuijuanZhang Guogang - Thermal proteome profiling (TPP) and proteome integral solubility alteration (PISA) assays measure drug-target interactions by monitoring protein thermal stability across the proteome. While detergents are routinely used in lysate-based thermal profiling, the field lacks consensus on whether detergents should be present during the melting step or only added afterward as an extraction buffer, and whether detergent identity matters for this choice. Here, we evaluate how commonly used detergents and the timing of their use in thermal stability workflows affect proteome-wide thermal stability and PISA hit calling in TF-1 lysates. We find that NP-40 and DDM produce highly correlated melting profiles when used exclusively as post-melt extraction buffers, but diverge substantially when present during the melting step. DDM in particular prevents the thermally-induced loss in solubility of large classes of proteins, such as cell surface proteins, and these effects propagate directly into PISA hit calling. Performing the PISA melt in DDM versus NP-40 results in the gain and loss of distinct drug-target interactions for both the PAK4 inhibitor PF-3758309 and the PLK1 inhibitor volasertib. Notably, DDM enables detection of a volasertib-TMEM97 interaction that was previously not detected in NP-40. However, we also find that the stabilization effects of DDM mask the identification of some known PISA hits for these drugs. We further introduce a four-parameter logistic model of protein melting to aid in modeling of these findings and a linear regression framework for PISA hit calling that outperforms pairwise t-tests in low-replicate settings. Together, these results establish detergent selection as a tunable experimental variable in thermal profiling and suggest that some drug-target engagements previously attributed exclusively to intact-cell context may be recoverable in lysates with appropriate buffer conditions. - Source: PubMed
Publication date: 2026/07/24
Sniezek CatherineGlukhova Veronika ASchmitz ChristianVlajic KatarinaSchweppe Devin K