IPA-3

• CAT Number: I003523
• CAS Number: 42521-82-4
• Molecular Formula: C₂₀H₁₄O₂S₂
• Molecular Weight: 350.45
• Purity: ≥95%
• Target: PAK1
• Solubility: DMSO 70mg/mL; Water <1 mg/mL; Ethanol 7 mg/mL
• Storage: 3 years -20C powder
• IC50: 2.5uM; 1.92 ± 0.2 μM( Dissociation constant) [1]
• InChI: InChI=1S/C20H14O2S2/c21-17-11-9-13-5-1-3-7-15(13)19(17)23-24-20-16-8-4-2-6-14(16)10-12-18(20)22/h1-12,21-22H
• InChIKey: RFAXLXKIAKIUDT-UHFFFAOYSA-N
• SMILES: C1=CC=C2C(=C1)C=CC(=C2SSC3=C(C=CC4=CC=CC=C43)O)O

IPA-3 is a selective non-ATP competitive PAK1 inhibitor with IC50 of 2.5 μM, no inhibition to group II PAKs (PAKs 4-6).IC50 Value: 2.5uM; 1.92 ± 0.2 μM( Dissociation constant) [1]Target: PAK1in vitro: Saturable binding of IPA-3 to full-length Pak1 was observed with an apparent dissociation constant of 1.92 ± 0.2 μM, consistent with the reported IC50 of 2.5 μM. IPA-3 bound the isolated RD with an even higher apparent affinity (0.1 ± 0.01 μM) whereas the kinase domain showed a weaker interaction. IPA-3 blocks activation of PAK2 at Ser192/197 that antagonises PAK/’s interaction with Pix. Accordingly, Pix-mediated Rac1 activation is decreased in IPA-3 treated schwannoma cells, indicating that PAK acts upstream of Rac [2]. In K562 cells, both chorein silencing and PAK1 inhibition with IPA-3 decreased phosphorylation of Bad, a Bcl2-associated protein, promoting apoptosis by forming mitochondrial pores, followed by mitochondrial depolarization, DNA fragmentation, and phosphatidylserine exposure at the cell surface, all hallmarks of apoptosis [3].in vivo: Inhalation of the small molecule synthetic Pak1 inhibitor, IPA3, also significantly reduced in vivo airway responsiveness to ACh and 5-hydroxytryptamine (5-Ht) in wild type mice. IPA3 inhibited the contractility of isolated human bronchial tissues to ACh, confirming that this inhibitor is also effective in human airway smooth muscle tissue [4].

Reference

1:Toxicity and anti-angiogenicity evaluation of Pak1 inhibitor IPA-3 using zebrafish embryo model. Jagadeeshan S, Sagayaraj RV, Paneerselvan N, Ghouse SS, Malathi R.Cell Biol Toxicol. 2017 Feb;33(1):41-56. doi: 10.1007/s10565-016-9358-5. Epub 2016 Aug 31. PMID: 27581547 2:Liposome-mediated delivery of the p21 activated kinase-1 (PAK-1) inhibitor IPA-3 limits prostate tumor growth in vivo. Al-Azayzih A, Missaoui WN, Cummings BS, Somanath PR.Nanomedicine. 2016 Jul;12(5):1231-9. doi: 10.1016/j.nano.2016.01.003. Epub 2016 Mar 3. PMID: 26949163 3:Inhibition of p21-Activated Kinase 1 by IPA-3 Promotes Locomotor Recovery After Spinal Cord Injury in Mice. Ji X, Zhang Y, Zhang L, Chen H, Peng Y, Tang P.Spine (Phila Pa 1976). 2016 Jun;41(11):919-25. doi: 10.1097/BRS.0000000000001491. PMID: 26863260 4:Inhibition of p21-activated kinase 1 by IPA-3 attenuates secondary injury after traumatic brain injury in mice. Ji X, Zhang W, Zhang L, Zhang L, Zhang Y, Tang P.Brain Res. 2014 Oct 17;1585:13-22. doi: 10.1016/j.brainres.2014.08.026. Epub 2014 Aug 20. PMID: 25148711 5:Group I PAK inhibitor IPA-3 induces cell death and affects cell adhesivity to fibronectin in human hematopoietic cells. Kuželová K, Grebeňová D, Holoubek A, Röselová P, Obr A.PLoS One. 2014 Mar 24;9(3):e92560. doi: 10.1371/journal.pone.0092560. eCollection 2014. PMID: 24664099 Free PMC Article6:IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation. Wong LL, Lam IP, Wong TY, Lai WL, Liu HF, Yeung LL, Ching YP.PLoS One. 2013 Jul 19;8(7):e68843. doi: 10.1371/journal.pone.0068843. Print 2013. PMID: 23894351 Free PMC Article