ChEMBL ligand: CHEMBL3265274
endoplasmic reticulum to nucleus signaling 1/Serine/threonine-protein kinase/endoribonuclease IRE1 in Human [ChEMBL: CHEMBL1163101] [GtoPdb: 2020] [UniProtKB: O75460] There should be some charts here, you may need to enable JavaScript!

DB	Assay description	Assay Type	Standard value	Standard parameter	Original value	Original units	Original parameter	Reference
endoplasmic reticulum to nucleus signaling 1/Serine/threonine-protein kinase/endoribonuclease IRE1 in Human (target type: SINGLE PROTEIN) [ChEMBL: CHEMBL1163101] [GtoPdb: 2020] [UniProtKB: O75460]
ChEMBL	Inhibition of human recombinant puritin-His-tagged IRE-1 RNase expressed in SF21 cells using XBP-1 RNA stem loop as substrate incubated for 30 mins prior to substrate addition measured after 2 hrs by FRET-suppression assay	B	7.33	pIC50	47	nM	IC50	J Med Chem (2014) 57: 4289-4301 [PMID:24749861]
ChEMBL	FRET-suppression assay: All compounds were evaluated by FRET-suppression assay in side-by-side experiments using 21b as a control inhibitor (Table 2). Protection of the aldehyde group in 21b as the 1,3-dioxane or dithiane acetal (24 and 25) resulted in weaker IRE-1 inhibitory activity. Alkylation of the phenol oxygen (compounds 26, 27, and 35) resulted in a complete loss of potency below 20 mM. The N-acyl derivative 29 exhibited an IC50 value of 312 nM while N-alkyl analogs 30-33 were found to be slightly more potent. N-benzyl analog 31 was almost 3-fold more active than the corresponding fluorinated derivative 32. Guanidinylation to give 34 resulted in a notable increase in potency (IC50=47 nM) relative to the parent compound, though solubility decreased. Ketone 36, vinyl sulfone 38, and Weinreb amide 42 showed no significant IRE-1 RNase inhibitory activity below 20 mM. However, electrophilic compounds 37, 40, and 41 displayed moderate potency (1-5 mM) in vitro. Also of note, 1,3-dioxane derivative 24 exhibited an in vitro IC50 of 3.1 mM, whereas the corresponding 1,3-dithiane analog 25 displayed more than 5-fold weaker activity. To confirm that the enhanced inhibitory activity of 24 is not simply a function of a labile aldehyde masking group, stability studies in assay buffer were carried out; no significant decomposition of the 1,3-dioxane moiety over 12 hours was observed.	B	7.33	pIC50	47	nM	IC50	US-10323013-B2. Inhibitors of the IRE-1/XBP-1 pathway and methods of using thereof (2019)
GtoPdb	Inhibition of RNAse activity.	-	7.33	pIC50	47	nM	IC50	J Med Chem (2014) 57: 4289-301 [PMID:24749861]

ChEMBL data shown on this page come from version 36:

Zdrazil B, Felix E, Hunter F, Manners EJ, Blackshaw J, Corbett S, de Veij M, Ioannidis H, Lopez DM, Mosquera JF, Magarinos MP, Bosc N, Arcila R, Kizilören T, Gaulton A, Bento AP, Adasme MF, Monecke P, Landrum GA, Leach AR. (2024). The ChEMBL Database in 2023: a drug discovery platform spanning multiple bioactivity data types and time periods. Nucleic Acids Res., 52(D1). DOI: 10.1093/nar/gkad1004. [EPMCID:10767899] [PMID:37933841]
Davies M, Nowotka M, Papadatos G, Dedman N, Gaulton A, Atkinson F, Bellis L, Overington JP. (2015) 'ChEMBL web services: streamlining access to drug discovery data and utilities.' Nucleic Acids Res., 43(W1). DOI: 10.1093/nar/gkv352. [EPMCID:25883136]