NU223612 

NU223612 is a potent PROTAC (PROTACs) that degrades indoleamine 2,3-dioxygenase 1 (IDO1) (Indoleamine 2,3-Dioxygenase (IDO)) with a K_d 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].

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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 C_max of 2 μM and a half-life of 8.3 h in brain tissue. In plasma, C_max 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 C_max of NU223612 in serum and brain samples^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

890.99

C₄₉H₅₅FN₆O₉

2759420-43-2

O=C([C@H](C)[C@@]1([H])CC[C@](C2=CC=NC3=CC=C(F)C=C23)([H])CC1)NC4=CC=C(OC5CCN(C(CCOCCOCCNC6=CC=CC(C(N7C(CC8)C(NC8=O)=O)=O)=C6C7=O)=O)CC5)C=C4

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [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.  [Content Brief]