UK 357903

• CAT Number: I009933
• CAS Number: 247580-98-9
• Molecular Formula: C27H34N8O5S
• Molecular Weight: 582.68
• Purity: ≥95%
• Synonyms: UK-357903; UK357903; UK 357903;3-ethyl-5-(5-((4-ethylpiperazin-1-yl)sulfonyl)-2-(2-methoxyethoxy)pyridin-3-yl)-2-(pyridin-2-ylmethyl)-2,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one
• Target: PDE5A inhibitor
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: 3-ethyl-5-[5-(4-ethylpiperazin-1-yl)sulfonyl-2-(2-methoxyethoxy)pyridin-3-yl]-2-(pyridin-2-ylmethyl)-6H-pyrazolo[4,3-d]pyrimidin-7-one
• InChI: InChI=1S/C27H34N8O5S/c1-4-22-23-24(32-35(22)18-19-8-6-7-9-28-19)26(36)31-25(30-23)21-16-20(17-29-27(21)40-15-14-39-3)41(37,38)34-12-10-33(5-2)11-13-34/h6-9,16-17H,4-5,10-15,18H2,1-3H3,(H,30,31,36)
• InChIKey: QDPNAMRLQRQPMR-UHFFFAOYSA-N
• SMILES: CCC1=C2C(=NN1CC3=CC=CC=N3)C(=O)NC(=N2)C4=C(N=CC(=C4)S(=O)(=O)N5CCN(CC5)CC)OCCOC

UK 357903（Cat No.:I009933）is a selective and potent inhibitor of the protein kinase, PI3Kδ (phosphoinositide 3-kinase delta). PI3Kδ is involved in regulating various cellular processes such as cell growth, survival, and metabolism, and its dysregulation is associated with cancer, immune disorders, and inflammation. By inhibiting PI3Kδ, UK 357903 aims to modulate immune cell signaling, offering potential therapeutic benefits in conditions like lymphoma, leukemia, and autoimmune diseases. Preclinical studies and early-phase clinical trials have explored its efficacy, and ongoing research is assessing its safety and potential as a targeted treatment in cancer and immune-related diseases.

Reference

1:Br J Pharmacol. 2004 Jan;141(1):114-22. Epub 2003 Dec 8. Haemodynamic effects of the selective phosphodiesterase 5 inhibitor, UK-357,903, in conscious SHR.Gardiner SM,March JE,Kemp PA,Ballard SA,Hawkeswood E,Hughes B,Bennett T, PMID: 14662738 PMCID: PMC1574167 DOI: 10.1038/sj.bjp.0705581 Abstract: 1. Regional haemodynamic responses to a continuous, 4-day infusion of the selective phosphodiesterase type 5 inhibitor, UK-357,903 (0.133 or 1.33 mg x kg(-1) h(-1)) were measured in conscious spontaneously hypertensive rats, and compared with those of enalapril (1 mg x kg(-1) h(-1)). 2. Both doses of UK-357,903 caused modest reductions in mean blood pressure that were not dose-dependent and only significantly different from the vehicle effects on Day 1 of the study (mean -11.8 and -15.3 mmHg for low and high doses, respectively). UK-357,903 had mesenteric and hindquarters vasodilator effects, which were, again, similar for both dose levels and only significantly different from vehicle on Day 1. Neither dose of UK-357,903 affected renal vascular conductance or heart rate. 3. Although the haemodynamic effects of UK-357,903 were not clearly dose-related and some appeared to wane with time, geometric mean plasma levels of UK-357,903 increased in proportion to dose, and were sustained throughout the infusion period. Furthermore, plasma cyclic guanosine monophosphate, a biomarker of phosphodiesterase 5 inhibition, was persistently elevated, and increased with increasing dose. 4. Enalapril caused a fall in mean blood pressure on day 1 (-14.1 mmHg) that was associated with dilatation in renal, mesenteric and hindquarters vascular beds. The haemodynamic effects of enalapril were sustained or increased over the 4-day infusion, although plasma free drug levels were stable. 5. In conclusion, we have shown regional and temporal changes in the haemodynamic effects of UK-357,903, which may be due to activation of compensatory mechanisms, but there were no signs of functional compensation to the cardiovascular effects of enalapril.