TGF-β Receptor Antagonist

LSKL, Inhibitor of Thrombospondin (TSP-1) is a latency-associated protein (LAP)-TGFβ derived tetrapeptide and a competitive TGF-β1 antagonist. LSKL, Inhibitor of Thrombospondin (TSP-1) inhibits the binding of TSP-1 to LAP and alleviates renal interstitial fibrosis and hepatic fibrosis. LSKL, Inhibitor of Thrombospondin (TSP-1) suppresses subarachnoid fibrosis via inhibition of TSP-1-mediated TGF-β1 activity, prevents the development of chronic hydrocephalus and improves long-term neurocognitive defects following subarachnoid hemorrhage (SAH). LSKL, Inhibitor of Thrombospondin (TSP-1) can readily crosse the blood-brain barrier.

GLPG3312 (Compound 28) is an orally active SIK inhibitor with IC₅₀ values of 2.0 nM, 0.7 nM and 0.6 nM for SIK1, SIK2 and SIK3, respectively. GLPG3312 exhibits anti-inflammatory and immunomodulatory activity in vitro on human primary myeloid cells and in vivo in mouse models. GLPG3312 has good oral bioavailability and can be used for research on inflammatory and immune diseases.

LSKL, Inhibitor of Thrombospondin (TSP-1) TFA is a latency-associated protein (LAP)-TGFβ derived tetrapeptide and a competitive TGF-β1 antagonist. LSKL, Inhibitor of Thrombospondin (TSP-1) TFA inhibits the binding of TSP-1 to LAP and alleviates renal interstitial fibrosis and hepatic fibrosis. LSKL, Inhibitor of Thrombospondin (TSP-1) TFA suppresses subarachnoid fibrosis via inhibition of TSP-1-mediated TGF-β1 activity, prevents the development of chronic hydrocephalus and improves long-term neurocognitive defects following subarachnoid hemorrhage (SAH). LSKL, Inhibitor of Thrombospondin (TSP-1) TFA can readily crosse the blood-brain barrier.

LAE-102 is the selective anti-ActRIIA (activin receptor type IIA or ACVR2) monoclonal antibody. LAE-102 increases muscle mass and reduces fat mass. LAE102 can increase serum activin A levels in vivo. LAE-102 is promising for research of obesity.

IMM-H007 (WS070117) is an orally active and potent AMPK (AMP-activated protein kinase) activator and TGFβ1 (transforming growth factor β1) antagonist. IMM-H007 has protective effects in cardiovascular diseases via activation of AMPK. IMM-H007 negatively regulates endothelium inflammation through inactivating NF-κB and JNK/AP1 signaling. IMM-H007 inhibits ABCA1 degradation. IMM-H007 resolves hepatic steatosis in HFD-fed hamsters by the regulation of lipid metabolism. IMM-H007 can be used for the research of nonalcoholic fatty liver disease (NAFLD) and inflammatory atherosclerosis.

Ramatercept (ACE-031) is a soluble ActRIIB receptor and can be used as a soluble activin receptor 2 (ACVR2) antagonist. Ramatercept inhibits the signal pathway of muscle growth inhibition and has potential application in muscle atrophy.

NUCC-555 is an activin antagonist. NUCC-555 interacts with Trp25, Trp28, Phe55, Tyr93, Lys103, and Asn107 in the Activin A binding pocket. NUCC-555 blocks Activin A-mediated hepatic stellate cells (HSCs) activation. NUCC-555 promotes liver regeneration and halts fibrosis progression in chronic liver disease models. NUCC-555 inhibits Activin A-mediated ovarian cell proliferation. NUCC-555 decreases FSH levels in ovariectomized mice.

SRI-35241 is a thrombospondin TSP-1 inhibitor with a pIC₅₀ of 8.12 nM against human targets. SRI-35241 inhibits the binding of TSP-1 to latent transforming growth factor-β-associated peptide (LAP) and blocks the activation of TGF-β. SRI-35241 shows a certain time-dependent property, with a plasma half-life of 1.8 h after intravenous administration. SRI-35241 can be used for the research of multiple myeloma and fibrotic diseases.

sTGFBR3 antagonist 1 (Compound p24) is an antagonist for soluble transforming growth factor beta receptor 3 (sTGFBR3), thus activates TGF-β signaling pathway, and inhibits IκBα/NF-κB signaling pathway. sTGFBR3 antagonist 1 inhibits NO-release in LPS (HY-D1056) -induced BV2 cells with an IC₅₀ of 0.52 μM. sTGFBR3 antagonist 1 exhibits anti-inflammatory and neuroprotective activities with blood brain barrier (BBB) permeability. sTGFBR3 antagonist 1 can be used in Alzheimer’s Disease research.