CS-2265

CS-2265化学性质

储存条件 :2-8°C
溶解度 :DMSO:25.0(Max Conc. mg/mL);49.01(Max Conc. mM)
Ethanol:25.0(Max Conc. mg/mL);49.01(Max Conc. mM)
PBS buffer (pH 7.2):5.0(Max Conc. mg/mL);9.8(Max Conc. mM)
DMF:30.0(Max Conc. mg/mL);58.82(Max Conc. mM)
形态 :powder
颜色 :white to beige
InChIKey :MULKOGJHUZTANI-JEGYXLSDNA-N
SMILES :C(C1CC1)N1C2=CC=CC=C2C=C1C1=NC2=CC(C(N3CC[C@@H](O)[C@@H](N)C3)=O)=CC(OC)=C2N1C.Cl |&1:22,24,r|

安全信息

CS-2265性质、用途与生产工艺

生物活性 GSK484 HCl 是苯并咪唑的衍生物，是一种选择性的、可逆的 peptidylarginine deiminase 4 (PAD4) 的抑制剂，在无钙的情况下IC50值为50 nM。
靶点
Target Value
PAD4
(in the absence of Calcium) 50 nM
体外研究

GSK484 demonstrates high affinity binding to the low-calcium form of PAD4 with IC ₅₀ s of 50 nM and 250 nM in the absence of Calcium (0 mM) and Calcium (2 mM), respectively. GSK484 also inhibits PAD4 citrullination (at 0.2 mM Calcium) of benzoyl-arginine ethyl ester (BAEE) substrate in a concentration-dependent manner, as detected using an NH ₃ release assay.
体内研究

To address whether PAD4 inhibition can suppress cancer-associated kidney injury, MMTV-PyMT mice are treated with the PAD4 inhibitor GSK484 at 4 mg/kg daily for one week. This dose suppress the elevated number of neutrophils undergoing NETosis in peripheral blood in mice with cancer. In parallel, the total protein level in urine from MMTV-PyMT mice is significantly reduced compared with untreated tumor-bearing mice, further supporting an improved functional status of the kidneys after GSK484 treatment. Administration of GSK484 at a dose of 4 mg/kg daily during one week reverts signs of kidney dysfunction in tumor-bearing mice to the same extent as DNase I treatment, without any detectable signs of toxicity.