LTβR-IN-1

• CAT Number: I046112
• CAS Number: 2189366-77-4
• Molecular Formula: C18H16N4O2
• Molecular Weight: 320.35
• Purity: ≥95%
• Synonyms: (2R)-N-(1H-benzimidazol-2-yl)-2-(3-oxo-1H-isoindol-2-yl)propanamide
• InChI: InChI=1S/C18H16N4O2/c1-11(22-10-12-6-2-3-7-13(12)17(22)24)16(23)21-18-19-14-8-4-5-9-15(14)20-18/h2-9,11H,10H2,1H3,(H2,19,20,21,23)/t11-/m1/s1
• InChIKey: PWSSISUOJZBZFT-LLVKDONJSA-N
• SMILES: CC(C(=O)NC1=NC2=CC=CC=C2N1)N3CC4=CC=CC=C4C3=O

LTβR-IN-1 is a potent, selective lymphotoxin β receptor (LTβR) inhibitor. LTβR-IN-1 also selectively inhibits the nuclear translocation of p52 depended on TNF12A, instead of the nuclear translocation of p65 mediated by TNF-α receptor. LTβR-IN-1 regulates the NF-kB signaling pathway IN a ligand-independent manner[1].
LTβR-IN-1 (compound 919278) (1 nM-100 μM; 30 min) inhibits p52 nuclear translocation in response to stimulation with Anti-LTβR or TWEAK (20 ng/mL, respectively; 4 h) with IC50s of 0.169 μM and 0.167 μM, respectively[1].
LTβR-IN-1 (3 nM-30 μM; 45 min) reduces the binding affinities of both CDK12 and its associated protein, CCNK in both TWEAK-stimulated and control U-2 OS cells, with IC50s of 50-61 nM for CDK12 and 29-68 nM for CCNK, respectively[1].
LTβR-IN-1 reduces the mRNA abundance of MAP3K14 in with an IC50 value of 0.32 μM in U-2 OS cells[1].
LTβR-IN-1 (1-10 μM; 30 min) decreases the phosphorylation of serine-2 (Ser2) on the C-terminal domain (CTD) of RNA polymerase (Pol) II[1].
LTβR-IN-1 regulates the noncanonical pathway in a ligandindependent manner and selectively inhibits the noncanonical pathway while sparing the canonical NF-kB signaling pathway[1].

Reference

[1]. Henry KL, et al. CDK12-mediated transcriptional regulation of noncanonical NF-κB components is essential for signaling. Sci Signal. 2018 Jul 31;11(541).
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