Inhibitors?Screening Libraries?ProteinsMedChemExpressITK degrader 1Cat
. No.:HY-149917分子式:C??H??F?N??O?分子量:943.02作用靶点:Itk作用通路:Protein Ty
rosine Kinase/RTK储存方式:Please store the product under the recommen
ded conditions in the Certificate of Analysis.BIOLOGICAL ACTIVITY
生物活性ITK degrader 1 是一种高度选择性的白细胞介素 2 诱导的 T 细胞激酶 (ITK) 降解剂 (DC50=3.
6 nM)。ITKdegrader 1 快速、持久地诱导 ITK 降解，并抑制体内抗 CD3 抗体刺激的 IL-2 分泌 (EC5
0=35.2 nM，Jurkat 细胞)。ITK degrader 1 也显示出良好的血浆暴露水平。体外研究ITK degrade
r 1 (compound 28) (0.001-3 μM; 12 h) dose-dependently decreases t
he protein levels of ITK inJurkat cells [1].Western Blot Analysis
[1]Cell Line:Jurkat cellsConcentration:0.001 μM, 0.003 μM, 0.1 μ
M, 0.3 μM, 1 μM, 3 μMIncubation Time:12 hResult:Exhibited strong
ITK degradation potencies in a dose-dependent manner. Even rapidl
yled to significant ITK protein downregulation after 1 h incubati
on.体内研究ITK degrader 1 (compound 28) (20 mg/kg; ip; single dose) s
ignificantly degrades ITK protein 2 h, 8 h, and 16h after treatme
nt on mice. ITK degrader 1 (25 mg/kg; ip; single dose) also inhib
its inhibits IL-2 secretion 6 hafter treatment in vivo in anti-CD
3 monoclonal antibody (mAb)-induced IL-2 mouse model [1].Pharmaco
kinetic Analysis in Balb/c Mice [1]RouteDose (mg/kg)AUC0-t (ng·h/
mL)AUC0-∞ (ng·h/mL)T1/2 (h)Vz (L/kg)Cl (mL/min/kg)Cmax (ng/mL)MRT
last (h)Bioavailability (%) i.v.515138154154.3920575.449104.42/1/
2MedChemExpresswww.MedChemExpress.cnip1025931272615.7530556.13423
5.8488.4%Animal Model:Balb/c mice, and anti-CD3 mAb-induced IL-2
mouse model [1]Dosage:20 mg/kg, 25 mg/kgAdministration:IP; singel
doseResult:Successfully delivered to the peripheral blood and sp
leen tissue, eliciting efficient, rapid,and prolonged ITK degrada
tion starting at 2 h and lasting for at least 16 h with 20 mg/kgd
ose in Balb/c mice.Efficiently suppressed the production of cytok
ine IL-2, resulting in a reduction of over70% compared to the veh
icle group with 25 mg/kg dose.REFERENCESZhou D, et al. Discovery
of Potent and Highly Selective Interleukin-2-Inducible T-Cell Kin
ase Degraders with In Vivo Activity. J Med Chem. 2023 Apr 13;66(7
):4979-4998.McePdfHeightCaution: Product has not been fully validated for medical applications.For research use only.2/2MedChemExpress |
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