Immunology and Inflammation

LHC-165 is an agonist of TLR7. It also has the potential to treat solid tumors.

IRAK4-IN-11 (compound 6) is a potent inhibitor of IRAK4 with an IC 50 of 0.008 μM. IRAK4-IN-11 exhibits cell pIRAK4 potencies with an IC 50 of 0.19 μM [1].

Galectin-8-IN-1 selectively binds galectin-8N with 48 μM affinity, 15x more than galectin-3.

PVTX-405 is a selective oral IKZF2 molecular glue degrader with a DC50 of 0.7 nM and a maximum degradation (Dmax) of 91%. It enhances degradation efficiency, significantly reduces off-target degradation, and minimizes hERG inhibition with an IC50 of 48 µM. PVTX-405 effectively inhibits MC38 tumor growth in Crbn391VC57BL/6 mouse xenograft models and shows superior synergistic anticancer effects when combined with immune checkpoint therapies (ICTs) such as anti-PD1 or anti-LAG3 antibodies.

ASP8731 is a selective inhibitor of BACH1 that prevents inflammation and vascular occlusion, and induces fetal hemoglobin in sickle cell disease.

IL-17 modulator 5 is a IL-17 inhibitor, with an IC 50 of 1 nM .

(S,R,S)-AHPC-Boc derivative 1 (Compound 80-9; VH032-Boc derivative 1) is a selective proteasomal degrader targeting MALT1, which recruits the E3 ubiquitin ligase CRBN to form a ternary complex with MALT1. This interaction leads to the ubiquitination and subsequent proteasomal degradation of MALT1. By disrupting the CBM complex, (S,R,S)-AHPC-Boc derivative 1 inhibits the NF-κB signaling pathway and shows potential in inducing apoptosis in ABC-DLBCL cells. It holds promise for research into MALT1-dependent cancers, such as diffuse large B-cell lymphoma (DLBCL).

Compound O15, an Osthole derivative, is a potent Nrf2 agonist with an EC50 of 2.9 μM; it inhibits Keap1-Nrf2 binding and Nrf2 ubiquitination.

Pentacyclic triterpene, Anti-inflammatory 13 inhibits DAMP/PAMP inflammation models.

(S)-MALT1-IN-5: Potent MALT1 protease inhibitor, may help in abnormal T/B-cell signalling and MALT1-linked diseases.

STING-IN-11 is a potent, orally bioavailable STING inhibitor (IC₅₀ = 37.8 nM) that blocks STING protein palmitoylation and downstream signaling.

TBK1/IKKε-IN-1 is a dual inhibitor of TBK1 and IKKε (IC50s of <100 nM).

TLR4/JNK/NF-κB-IN-1 (Racemic-11k) is an inhibitor of TLR4, JNK, and NF-κB. It suppresses NO production in LPS-stimulated RAW264.7 cells with an IC50 of 23.2 µM. By inhibiting TLR4 expression and reducing JNK phosphorylation, TLR4/JNK/NF-κB-IN-1 prevents NF-κB activation. This leads to a decrease in the transcription of inflammation-related genes, reducing the expression of iNOS and COX-2, and the production of inflammatory mediators such as NO, PGE2, and TNF-α, thereby exhibiting anti-inflammatory activity. TLR4/JNK/NF-κB-IN-1 holds potential in the study of inflammatory diseases, including rheumatoid arthritis and various other inflammatory conditions.

Anti-osteoporosis agent-11 (compound 3k) is an anti-osteoporosis compound targeting osteoclasts. It exhibits its most prominent effect by inhibiting osteoclast differentiation, with an IC50 value of 0.36 μM. Additionally, Anti-osteoporosis agent-11 suppresses osteoclast formation, bone resorption, and the expression of osteoclast-specific genes by blocking the RANKL-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways.

KCC2 Modulator-2 (example 53) is a regulator of KCC2 with an EC50 of 0.215 μM. It is used in the research of neurological diseases.

dCK1α-2 is an orally effective CK1α molecular glue (Molecular Glue) degrader that targets p53 pathway-related targets. It demonstrates antitumor efficacy in mouse models by enhancing the expression of p53-related genes.

SLC7A11-IN-2 (Compound 1) is an inhibitor of SLC7A11/xCT. It disrupts the oxidative balance in HeLa cells by decreasing intracellular glutathione levels and increasing oxidative stress, thereby inducing cell death with an IC50 of 10.23 μM. Molecular dynamics simulations have demonstrated that SLC7A11-IN-2 exhibits a stronger binding affinity to SLC7A11 compared to Erastin. This compound is useful for research in the field of cervical cancer.

TLR7/8 agonist 7 activates immune cells, useful in ISAC synthesis and immunity research.