IFNAR Agonist

RO8191 (CDM-3008), an imidazonaphthyridine compound, is an orally active and potent interferon (IFN) receptor agonist. RO8191 directly binds to IFNα/β receptor 2 (IFNAR2) and activates IFN-stimulated genes (ISGs) expression and JAK/STAT phosphorylation. RO8191 shows antiviral activity against both HCV and EMCV with an IC₅₀ of 200 nM for HCV replicon. RO8191 is a cccDNA modulator (CDM) through interferon-like activity and has anti-HBV activity.

Interferon alfa-2b is a type I interferon that activates novel genes and exerts potent antiviral and antiproliferative activity on target cells. Signaling by Interferon alfa-2b requires receptor-dependent activation of Stat1 and Stat2 to form a heterodimeric STAT that binds to the DNA-binding protein IRF-9 (p48) and forms ISGF-3 (IFN-stimulated gene factor 3). The driver genes are then further activated by ISGF-3 to achieve antiviral function.

IGRP(206-214) is a biological active peptide. IGRP(206-214) corresponds to residues 206-214 of murine islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP). IGRP(206-214) is T cells specific for proinsulin and IGRP induces diabetes in non-obese diabetic (NOD) mice.

STING agonist-45 is a selective STING agonist (EC₅₀ = 0.28 μM). STING agonist-45 activates the innate immune response through the cGAS-STING pathway, upregulating key markers such as p-TBK1 and IRF3. STING agonist-45 exhibits robust STING activation in human peripheral blood mononuclear cells (PBMCs), inducing the production of type I interferons (such as IFN-β) and downstream cytokines (such as TNF-α and IL-6). STING agonist-45 enhances anti-tumor immunity, inhibits tumor growth, and increases CD8⁺ T cell infiltration in mouse models. STING agonist-45 is promising for the study of STING-related diseases.

SM-276001 is a potent selective TLR7 agonist that can induce antitumor immune responses. SM-276001 is an orally active interferon (IFN) inducer.

PROTAC HPK1 Degrader-5 is a potent and orally active HPK1 PROTAC degrader (DC50 = 5.0 nM; Dmax ≥ 99%). PROTAC HPK1 Degrader-5 significantly inhibits SLP76 phosphorylation and enhanced ERK pathway activation through degrading HPK1, thereby stimulating IL-2 and IFN-γ release. PROTAC HPK1 Degrader-5 exhibits the ability to overcome the immunosuppressive effects imposed by PGE2, NECA or TGF-β. PROTAC HPK1 Degrader-5 alone efficaciously inhibits tumor growth in an MC38 syngeneic mouse model. PROTAC HPK1 Degrader-5 can be used for the study of tumor (such as colorectal cancer) immunotherapy.

Interferon receptor inducer-1 (compound 6) is an interferon (IFN) receptor inducer. Used accordingly in the treatment of a disorder in which the induction of interferon is involved.

Peginterferon alfa-2a is a PEG-modified interferon (IFN) alpha-2a. Peginterferon alfa-2a can be used for research of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection.

SF-9-2 is a PD-L1/PD-1 binding inhibitor (IC₅₀ = 24.9 nM). SF-9-2 inhibits epithelial-mesenchymal transition, migration, invasion, and proliferation of SK-N-SH cells, and also induces apoptosis and cell cycle arrest. SF-9-2 blocks PD-L1-induced SK-N-SH cell growth through the MAPK signaling pathway. SF-9-2 restores GSK-3β activity and enhances PD-L1 degradation through the ubiquitin-proteasome pathway. SF-9-2 inhibits tumor growth in the SK-N-SH NOG mouse model without significant toxicity. SF-9-2 also acts as an immune checkpoint inhibitor, blocking PD-L1 to restore T cell function. SF-9-2 can be used in neuroblastoma research.

KRN7000 analog 1 exhibits good Th1-biased immune response through induction of interferon-γ (IFN-γ) and reduction of interleukin-4 (IL-4). KRN7000 analog 1 is potential as an antitumor agent and vaccine adjuvant.

TLR7 agonist 29 (Compound 1) is the agonist for TLR7 with an EC₅₀ of 5.2 nM for human TLR7 (EC₅₀ for mouse TLR7 is 48.2 nM). TLR7 agonist 29 activates bone marrow-derived macrophages (BMDMs), stimulates myeloid cells in the tumor microenvironment, promotes the expression of PD-L1, CD86 and IFN-α. TLR7 agonist 29 can be used as payload for synthesis of ADC.

TLR7/8 agonist 13 is an orally active dual agonist of TLR7 (lowest effective concentrations (LEC) [hTLR7] = 1.6 μM) and TLR8 (LEC [hTLR8] = 1.6 μM). TLR7/8 agonist 13 exhibits agonistic activity against human peripheral blood mononuclear cells (hPBMCs) (LEC [hPBMC] = 0.5 μM). TLR7/8 agonist 13 induces endogenous IFNα, activating myeloid dendritic cells and monocytes toward a TH1 phenotype in mice and cynomolgus monkeys. TLR7/8 agonist 13 reduces viral load and HBV surface antigen expression in a mouse model of chronic AAV-HBV infection. TLR7/8 agonist 13 has the potential to indirectly induce IFNγ, which may promote HBV antigen-specific CD8 T cell-mediated responses. TLR7/8 agonist 13 can be used to study hepatitis B virus.