898044-15-0

Basic information

• Product Name: PF-3758309
• Synonyms: PF-3758309;(S)-N-(2-(diMethylaMino)-1-phenylethyl)-6,6-diMethyl-3-((2-Methylthieno[3,2-d]pyriMidin-4-yl)aMino)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxaMide;PF-03758309/PF03758309;N-[(1S)-2-(Dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide;PF-03758309;Pyrrolo[3,4-c]pyrazole-5(1H)-carboxaMide, N-[(1S)-2-(diMethylaMino)-1-phenylethyl]-4,6-dihydro-6,6-diMethyl-3-[(2-Methylthieno[3,2-d]pyriMidin-4-yl)aMino]-;N-[(1S)-2-(Dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide PF 3758309;X4Z
• CAS NO: 898044-15-0
• Molecular Formula: C25H30N8OS
• Molecular Weight: 490.6237
• Product Categories: Inhibitors
• Mol File: 898044-15-0.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• Density: 1.325±0.06 g/cm3(Predicted)
• Storage Temp.: -20C
• Solubility: ≥24.53 mg/mL in DMSO; insoluble in H2O; ≥101.4 mg/mL in EtOH with gentle warming and ultrasonic
• PKA: 12.82±0.40(Predicted)
• CAS DataBase Reference: PF-3758309(CAS DataBase Reference)
• NIST Chemistry Reference: PF-3758309(898044-15-0)
• EPA Substance Registry System: PF-3758309(898044-15-0)

Safety Data

• Hazardous Substances Data: 898044-15-0(Hazardous Substances Data)

Usage

Description

PF-3758309 is a pyrrolopyrazole inhibitor of PAK4 (p21-activated kinase), a protein involved in the regulation of cytoskeletal dynamics and cell survival. It is a small molecule compound that has been developed for its potential use in cancer therapy.
Used in Pharmaceutical Industry:
PF-3758309 is used as a targeted therapy agent for cancer treatment. It specifically inhibits the activity of PAK4, a key player in the Rho GTPase signaling pathway, which is often dysregulated in various types of cancer. By targeting PAK4, PF-3758309 can disrupt the signaling pathways that promote tumor growth, invasion, and metastasis, making it a promising candidate for cancer therapy.
Additionally, PF-3758309 is used in biological studies to investigate the role of PAK4 in cancer progression and to explore its potential as a therapeutic target. Researchers are interested in understanding the molecular mechanisms by which PF-3758309 exerts its anti-cancer effects, as well as its potential synergistic effects when combined with other cancer therapies.

Biological Activity

pf-3758309 is an inhbitor of pak4 with ic50 of 1.3 nm [1].p21-activated kinases (paks) are the family of serine/theronine kinases, which play important role in linking rho gtpase to cytoskeleton reorganization and nuclear signaling. pak4 is a member of paks family, specifically responsive for interacting with gtp bound form of cdc42 and jnk family. pak4 is involved in filopodia formation and may play a role in the reorganization of the actin cytoskeleton.biochemical study had identified that pf-3758309 was an atp-competitive inhibitor of pak4, which inhibited the kinase activity [1]. when pak4 was screened with a panel of tumor cell lines, it was found pf-3758309 inhibited the phosphorylation of pak4 substrate gef-h1, and also the pak4-induced anchorage-independent cell growth, with ic50 value of 1.3 nm and 4.7 ±3 nm respectively [1]. when pf-3758309 was screened with a panel of paks related kinases, it exhibited good potency and specificity for pak4 [1]. cell analysis con?rmed that pf-3758309 modulates pak4-dependent signaling nodes and identi?es unexpected links to additional p53pathways [1].

in vivo

activity of pf-3758309 was examined in a panel of human xenograft model, including hct116 and a549 model. twice daily oral administration of pf-3758309 (7.5-30 mg/kg bid) for 9-18 days resulted in significant inhibition of tumor growth in all the models. the tumor growth was shown to be caused by pak-dependent pathways in hct116 and a549 model. additionally, pf-3758309 was shown to regulate pak-associated cell proliferation and survival in certain models. therefore, pf-3758309 exhibited inhibitory activity on pak4 [1].

references

[1] murray b w et al. , small-molecule p21-activated kinase inhibitor pf-3758309 is a potent inhibitor of oncogenic signaling and tumor growth. proc natl acad sci usa. 2010, 107(20): 9446-9451.