canonical

RU-SKI 43 is a potent and selective hedgehog acyltransferase (Hhat) inhibitor with an IC50 of 850 nM. It exhibits anticancer activity and is a potential treatment for lung adenocarcinomas. RU-SKI 43 reduces Gli-1 activation through smoothening-independent non-canonical signaling and inhibits Akt and mTOR pathway activity.

Kasugamycin hydrochloride hydrate (Ksg (hydrochloride hydrate))(Ksg) specifically inhibits translation initiation of canonical but not of leaderless messenger RNAs. Ksg inhibition is thought to occur by direct competition with initiator transfer RNA

CP-456773 (MCC950 (CP-456773) and CRID3) is an effective and specific cytokine release inhibitor and NLRP3 inflammasome inhibitor. CP-456773 inhibits IL-1β secretion and caspase 1 processing. MCC950 blocked canonical and noncanonical NLRP3 activation at nanomolar concentrations. MCC950 specifically inhibited activation of NLRP3 but not the AIM2, NLRC4 or NLRP1 inflammasomes. MCC950 reduced IL-1β production in vivo and attenuated the severity of experimental autoimmune encephalomyelitis (EAE), a disease model of multiple sclerosis.

Apramycin(Nebramycin II) is an aminoglycoside antibiotic used in veterinary medicine. IC50 value:Target: Apramycin stands out among aminoglycosides for its mechanism of action which is based on blocking translocation and its ability to bind also to the eukaryotic decoding site despite differences in key residues required for apramycin recognition by the bacterial target. The drug binds in the deep groove of the RNA which forms a continuously stacked helix comprising non-canonical C.A and G.A base pairs and a bulged-out adenine. The binding mode of apramycin at the human decoding-site RNA is distinct from aminoglycoside recognition of the bacterial target, suggesting a molecular basis for the actions of apramycin in eukaryotes and bacteria. [1]. Apramycin, From Wikipedia

SJ000291942 is an activator of the canonical bone morphogenetic proteins (BMP) signaling pathway.

LF3 is a specific inhibitor of canonical Wnt signaling by disrupting the interaction between β-catenin and TCF4 (IC50 < 2 μM)

TRPC6-IN-1 is an inhibitor of the Transient Receptor Potential Canonical 6 Channel (TRPC6) (EC50: 4.66 μM).

Hyperforin dicyclohexylammonium salt is a transient receptor canonical 6 channel activator with antidepressant effect. It modulates Ca2+ levels by activating Ca2+-conducting non-selective canonical TRPC6 channels.

JW74 antagonizes LiCl-induced activation of the canonical Wnt signaling pathway (IC50: 420 nM).

Pyr3 is a selective transient receptor potential canonical channel 3 inhibitor. Pyr3 inhibits TRPC3-mediated Ca2+ influx in a dose-dependent manner(IC50 = 700 nM).

UAA crosslinker 1 hydrochloride is an amber codon used to incorporate non-canonical amino acids (ncAAs) into proteins in vivo by leveraging the promiscuous activity of specific wildtype and engineered aminoacyl-tRNA synthetases [1].

UAA crosslinker 1 hydrochloride is an Amber codon-activating agent used for incorporating non-canonical amino acids (ncAAs) into proteins in vivo by leveraging the promiscuous activity of specific wildtype and engineered aminoacyl-tRNA synthetases[1].

SU1261, an IKK inhibitor, exhibits Ki values of 10 nM for IKKα and 680 nM for IKKβ. It effectively inhibits non-canonical NF-κB signaling in U2OS osteosarcoma cells.

TRPC4 5-IN-3 (Compound 32) is an orally active inhibitor of transient receptor potential canonical channels 4 and 5 (TRPC4 5), with IC50 values of 3.6 nM and 5.5 nM, respectively. It inhibits the hERG channel with an IC50 of 6.5 µM. This compound demonstrates good metabolic stability in human, rat, and mouse liver microsomes. In mouse models, TRPC4 5-IN-3 exhibits antidepressant and anxiolytic effects and displays favorable pharmacokinetic properties, with an oral bioavailability of 87%.

JW 67 is an inhibitor of canonical Wnt pathway signaling. JW 67 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1.

ML204 is a novel potent antagonist that selectively modulates native TRPC4 C5 ion channels.

RBPI-3 is a canonical poly(ADP-ribose) glycohydrolase.

2'2'-cGAMP is a synthetic dinucleotide (CDN) that contains non-canonical 2'5'-phosphodiester bonds. It binds to the adapter protein stimulator of interferon genes , which is a component of the innate immune response that activates the type I interferon pathway when bound to cyclic dinucleotides. 2'2-cGAMP shows weaker binding to STING than 2'3'-cGAMP but binds more strongly than 3'3'-cGAMP , cyclic di-GMP , or 3'2'-cGAMP, which bind in the micromolar range (Kds = 1.04, 1.21, or 1.61 μM, respectively). Despite weaker binding, 2'2'-cGAMP induces IFN-β production in the same concentration range as 2'3'-cGAMP (EC50s = 15.8 and 19.4 nM, respectively, in L929 cells).

DTUN is a lipophilic hyponitrite radical initiator.1It initiates co-autoxidation of STY-BODIPY-embedded egg phosphatidylcholine liposomes when used at a concentration of 0.2 mM. DTUN has been used in fluorescence-enabled inhibited autoxidation (FENIX) assays for the development of ferroptosis inhibitors and the study of antioxidants in lipid membranes.1,2 1.Shah, R., Farmer, L.A., Zilka, O., et al.Beyond DPPH: Use of fluorescence-enabled inhibited autoxidation to predict oxidative cell death rescueCell Chem. Biol.26(11)1594-1607(2019) 2.Soula, M., Weber, R.A., Zilka, O., et al.Metabolic determinants of cancer cell sensitivity to canonical ferroptosis inducersNat. Chem. Biol.16(12)1351-1360(2020)

Potent TBK1 (TANK-binding kinase-1) inhibitor (IC50 = 6 nM). Inhibits the formation of autophagosomes in lung cancer cells. Newman et al (2012) TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-κB signalling. PLoS ONE 7 e50672 PMID:23209807 |McIver et al (2012) Synthesis and structure-activity relationships of a novel series of pyrimidines as potent inhibitors of TBK1/IKKe kinases. Bioorg.Med.Chem.Lett. 22 7169 PMID:23099093

3'3'-cGAMP is a second messenger produced in bacteria by specific dinucleotide cyclases. It contains canonical 3'5'-phosphodiester bonds and regulates chemotaxis, colonization, and other cellular functions. 3'3'-cGAMP shows weaker binding to the adapter protein stimulator of interferon genes (STING; Kd = 1.04 μM) than 2'2'-cGAMP and 2'3'-cGAMP but has similar binding affinity to 3'2'-cGAMP (Kd = 1.61 μM) and cyclic di-GMP . 3'3'-cGAMP induces IFN-β mRNA expression in L929 cells (EC50 = 40.5 nM).

β-Catenin-IN-37 is a selective inhibitor of the protein-protein interaction between β-Catenin and T-cell factor (Tcf), known as β-catenin/Tcf PPI. It effectively inhibits canonical Wnt signaling and impedes the growth of colorectal cancer cells SW480 and HCT116, with IC50 values of 20 μM and 31 μM, respectively.

NF-κB-IN-2 inhibits canonical NF-κB signaling induced by TNF-α in PC-3 cells.

SY-LB-35, a potent bone morphogenetic protein (BMP) receptor agonist, significantly enhances cell number and viability in the C2C12 myoblast cell line. It promotes cell cycle progression, particularly towards the S and G2 M phases. Additionally, SY-LB-35 activates both canonical Smad and non-canonical intracellular signaling pathways, including PI3K Akt, ERK, p38, and JNK [1].