rorα

Cholesterol is the primary sterol in mammals, accounting for approximately 20–25% of the plasma membrane structure. It plays a key role in regulating membrane fluidity, permeability, and protein function. As an endogenous agonist of estrogen-related receptor α (ERRα), cholesterol is widely involved in metabolic regulation and serves as a precursor for the synthesis of hormones and bile acids. It is commonly used in experimental models of hyperlipidemia.

A-9758 is a RORγ ligand and selective RORγt inverse agonist (IC50: 5 nM) that effectively suppresses IL-17A release, Th17 differentiation, and Th17 effector function, significantly attenuating IL-23 driven psoriasiform dermatitis.

SR1078 is an agonist of retinoic acid receptor-related orphan receptor (ROR)α/γ.

SR3335 (ML 176) is a selective inverse agonist of RORα that competitively inhibits the binding of 25-hydroxycholesterol to the ligand binding domain (Ki: 220 nM).

SR 1001 is an inverse agonist for RORα/RORγ (Kis: 172/111 nM).

Cabozantinib hydrochloride (XL184) is a potent pan-tyrosine kinases inhibitor that inhibits VEGFR2, c-Met, Kit, Axl, and Flt4 (IC50s: 0.035, 1.3, 4.6, 7 and 6 nM).

T0901317 is a potent and selective agonist for both LXR and FXR, with EC50 of ~50 nM and 5 μM, respectively; it inhibits nuclear factor/κB (NF/κB).

RORγ inverse agonist 1 has anti-inflammatory activity and can be used to treat rheumatism and psoriasis.

ROR agonist-1 is a potent and orally bioavailable inverse agonist of the retinoic acid receptor-related orphan receptor C2 (RORC2), demonstrating inhibition of IL-17A production from human primary TH17 cells with a pIC50 of 7.5.

RORγt agonist 1 is a potent, orally bioavailable agonist of RORγt(EC50 of 20.8 nM).

RORγt Inverse Agonist 3 is a potent, selective, and orally active inverse agonist of RORγ with EC50 values of 0.22 μM for hRORγ and 0.15 μM for RORγt (human IL-17 cells), respectively.

RORγt Inverse agonist 6 is an agonist of RORγt inverse. RORγt Inverse agonist 6 can be used in research on Th17-driven autoimmune diseases.

RORγt Inverse agonist 8 is a potent, selective, orally bioavailable RORγt inverse agonist (human RORγt-LBD) with an IC50 of 19 nM.

RORγt Inverse agonist 2 is a selective, orally active inverse agonist of RORγt, with an EC50 of 119 nM.

RORγt inverse agonist 32 (compound b14) exhibits oral activity and can be utilized in inflammatory research studies.

RORγt inverse agonist 34 (compound 5a) is an inverse agonist for RORγt, exhibiting an IC50 of 0.094 μM for the inhibition of RORγt-LBD. This compound is utilized in psoriasis research.

RORγ-IN-2 (Compound 22) is an inhibitor of RORγ, with a Ki value of 16.6 nM for hRORγ. It is useful for research in IL-17-dependent autoimmune diseases.

RORγt inverse agonist 33 (compound (R)-D4) is an orally bioavailable RORγt inverse agonist with an IC50 of 21 nM, playing a significant role in rheumatoid arthritis research.

RORγt inhibitor 4 (Compound 9a) is an orally active RORγt inhibitor capable of penetrating the central nervous system. It has been shown to improve experimental autoimmune encephalomyelitis.

PROTACROR1degrader-1 (Compound 11d) serves as a PROTAC degrader targeting the pseudokinase ROR1, with the capability of degrading ROR1 in NSCLC cells at a DC50 of 40-80 nM. It induces PARP cleavage and apoptosis in NCI-H23 cells. [Pink: ligand for target protein ROR1 ligand-1; Black: linker; Blue: ligand for VHL E3 ligase (S,R,S)-AHPC]

ROR1ligand-1 (9-1) serves as the ligand for PROTAC ROR1 degrader-1. By linking with ligands of either the VHL type or CRBN, the first selective and efficient ROR1 PROTAC molecule was designed and synthesized.

ROR1-IN-2 (compound 9I) is a potent and selective inhibitor of ROR1. It exhibits antiproliferative activity in various cancer cell lines and significantly inhibits tumor growth in vivo.

ROR1-IN-1 (Compound 19h) is an inhibitor of receptor tyrosine kinase-like orphan receptor 1 (ROR1) with a Ki of 0.10 μM. It inhibits the proliferation of cancer cell lines H1975, A549, and MDA-MB-231, with IC50 values of 0.36 μM, 1.37 μM, and 0.47 μM, respectively. In mice, ROR1-IN-1 demonstrates antitumor efficacy and exhibits favorable pharmacokinetic properties in a rat model.

RORγinverse agonist 2 (Compound 15) is a potent inverse agonist of the retinoic acid receptor-related orphan receptor RORγ, with IC50 values of 0.4 μM for Gal4-RORγ and 0.9 μM for full-length RORγ. This compound is useful for researching autoimmune diseases.