NU223612_product_DataBase

Bioactivity	NU223612 is a potent PROTAC (PROTACs) that degrades indoleamine 2,3-dioxygenase 1 (IDO1) (Indoleamine 2,3-Dioxygenase (IDO)) with a Kd of 640 nM. NU223612 potently degrades the IDO1 protein through CRBN-mediated proteasomal degradation. NU223612 is bound to CRBN with an affinity of 290 nM. NU223612 can cross the blood-brain barrier (BBB)[1].
Invitro	NU223612 (0.1-10 μM; 24 h) decreases IDO1 protein levels dose-dependently[1].A DC50 (the concentration of the NU223612 at which 50% of the IDO1 protein is degraded) of 0.3290 μM and 0.5438 μM in U87 and GBM43 cells is determined, respectively[1].NU223612 degrades IDO1 protein in multiple cell types, such as CD18 and PANC-1 human pancreatic cancer cells, OVCAR5 and SKOV3 human ovarian cancer cells, PC3 human prostate cancer cells, and the syngeneic GL261 mouse IDO1 cDNA-expressing (IDO1-O/E) glioma cell line[1].NU223612 equally degrades IDO1 protein levels in both the cytoplasmic and nuclear intracellular compartments in human GBM cells. NU223612 is able to penetrate subcellular compartments[1].NU223612 dose-dependently inhibits IDO1 enzyme activity resulting in decreased Kyn levels in cultured IFNγ-stimulated GBM cells. NU223612 inhibits both IDO1-mediated tryptophan metabolism as well as IDO1 non-enzyme-mediated NF-κB p65 transcription factor DNA binding activity[1]. Western Blot Analysis[1] Cell Line:
In Vivo	NU223612 (25 mg/kg; i.p.; once) decreases IDO1 protein in C57BL/6 with mIDO1 cDNA-expressing GL261 cells[1].NU223612 (25 mg/kg; i.p.; 5 days/week; for 3 weeks) leads to an increase in median overall survival as well as longer-term survival for up to 45 days post-tumor cell injection[1].Mass spectrometry analysis of NU223612 (25 mg/kg; i.p.; once) shows a Cmax of 2 μM and a half-life of 8.3 h in brain tissue. In plasma, Cmax is 365 μM and the half-life is 2.5 h. The binding of NU223612 to mouse brain homogenate using a 6 h equilibrium dialysis shows NU223612 to be 99.8% bound[1].Half-life, AUC, and Cmax of NU223612 in serum and brain samples[1].
Name	NU223612
CAS	2759420-43-2
Formula	C49H55FN6O9
Molar Mass	890.99
Transport	Room temperature in continental US; may vary elsewhere.
Storage	Please store the product under the recommended conditions in the Certificate of Analysis.
Reference	[1]. Lakshmi R Bollu, et al. Identification and Characterization of a Novel Indoleamine 2,3-Dioxygenase 1 Protein Degrader for Glioblastoma. J Med Chem. 2022 Nov 21.

PeptideDB

NU223612

CAS: 2759420-43-2 F: C49H55FN6O9 W: 890.99