TNFRSF5/CD40 Inhibitor

FZ1 peptide is a cyclic heptapeptide and also an integrin αvβ3 agonist. FZ1 peptide activates the FAK/PI3K-AKT/ERK pathway and upregulates VEGFC to promote angiogenesis. FZ1 peptide exhibits antibacterial activity in extracts of HA-c-FZ1 hydrogel; it inhibits LPS-induced proinflammatory cytokine secretion in RAW264.7 macrophages; it reduces H₂O₂-induced ROS levels; it increases the healing rate of scratch wounds. FZ1 peptide can be used in studies related to diabetic skin wounds.

Indole-4-carboxaldehyde is an ergot alkaloid precursor that regulates glycosylation and inflammation. Indole-4-carboxaldehyde upregulates Glo-1, inhibits MGO-induced NF-κB activation, and suppresses MGO-induced expression of TNF-α and IFN-γ. Indole-4-carboxaldehyde inhibits MGO-induced formation of advanced glycation end products (AGE) and expression of their receptor (RAGE). Indole-4-carboxaldehyde is a core metabolite produced in the pedicels of Summer Black grapes after exogenous gibberellin treatment, and it directly promotes fruit enlargement and fruit set of Summer Black grapes. Indole-4-carboxaldehyde can be used in studies related to hepatic steatosis and plant growth regulation.

2,5-Dihydroxyterephthalic acid is a carboxylic acid ligand with antioxidant properties, which serves as a building block for Zn²⁺-based metal-organic frameworks (MOFs). 2,5-Dihydroxyterephthalic acid forms stable coordination bonds with transition metal ions, inhibits metal center-water coordination to prevent MOF fluorescence quenching, and enhances the hydrophilicity of MOFs. 2,5-Dihydroxyterephthalic acid acts as a pharmaceutical intermediate to synthesize 2,5-dihydroxyterephthalamide derivatives. 2,5-Dihydroxyterephthalic acid is applicable to relevant research in fields such as organic synthesis.

DRI-C25441 is a potent blocker of CD40 and CD40L interaction, with an IC₅₀ of 0.36 μM. DRI-C25441 can inhibit the immune response induced by alloantigen. can inhibit CD40L induced activation of NF-κB signaling pathway. DRI-C25441 commonly is used in research on immune conditions .

Pentadecane is an orally active natural plant volatile alkane with anti-inflammatory, analgesic, antipyretic and anti-leishmanial activities. Pentadecane presents IC₅₀ values of 65.3 μM, 60.5 μM and 194.8 μM against Leishmania infantum promastigotes, amastigotes and intracellular amastigotes, respectively. Pentadecane downregulates the mRNA expression of TNF-α and IL-12 and inhibits the release of inflammatory mediators. Pentadecane arrests the cell cycle of Leishmania infantum and induces apoptosis. Pentadecane can be applied to the research of inflammation and leishmaniasis.

IKK2-IN-4 is an orally active and selective IKK-2 inhibitor (IC₅₀ = 0.025 μM) that also inhibits JNK-1 (IC₅₀ = 1.6 μM). IKK2-IN-4 blocks IκB phosphorylation and NF-κB activation, and inhibits JNK-1 kinase activity. IKK2-IN-4 inhibits TNF-α production in PBMCs. IKK2-IN-4 can be used for research on IKK-2-related diseases, such as autoimmune diseases.

Casuarinin is an orally active antiproliferative, anti-inflammatory, antifungal, virucidal and gastroprotective agent. Casuarinin upregulates the expression of p21/WAF1, Fas/APO‑1, mFasL, sFasL and HSP‑70, arrests cell cycle, induces apoptosis and inhibits cancer cell proliferation. Casuarinin inhibits TNF‑α-induced phosphorylation of MAPK and activation of NF‑κB, downregulates the expression of iNOS, NF‑κB, COX‑2 and ICAM‑1, and reduces the production of proinflammatory mediators. Casuarinin attenuates ethanol-induced activation of caspase‑3 and elevation of TNF‑α, inhibits the growth of Candida albicans, and inhibits HSV‑2. Casuarinin can be used in research related to mammary adenocarcinoma, inflammatory skin diseases, gastric ulcers, candidiasis and herpes simplex virus infections.

Pegevongitide (AV-001) is a Tie2 agonist. Pegevongitide resists the increased endothelial cell permeability induced by SARS-CoV-2 infection. Pegevongitide activates the angiogenin (angiogenin)/Tie2 signaling pathway. Pegevongitide reduces perivascular space dilation and upregulates perivascular Aquaporin-4 expression. Pegevongitide decreases the expression of TNF-α, PAI-1, CXCL9 and P-selectin, improves white matter integrity, enhances cognitive function and exerts neuroprotective effects. Pegevongitide improves white matter integrity in middle-aged rats with vascular dementia induced by multiple microinfarctions. Pegevongitide can be used in related research on diseases such as COVID-19 and vascular dementia.

EJMC-1 is a moderately potent TNF-α inhibitor with an IC₅₀ value of 42 μM.

Karacoline is an orally active PPARγ activator and ERK/JNK MAPK inhibitor. Karacoline restricts ROS production, maintains mitochondrial membrane potential, and inhibits pulmonary cell apoptosis. Karacoline inhibits NF-κB pathway activation, reduces acetylation levels of p65 and the expression of MMP14 and MMP9, enhances the expression of type II collagen (collagen II) and aggrecan (aggrecan), and suppresses extracellular matrix degradation. In a mouse model of sepsis-induced acute lung injury, Karacoline alleviates lung injury, inhibits the release of IL-1β, IL-6 and TNF-α, increases the Bcl-2/BAX ratio, and reduces caspase 3 expression. Karacoline can be used in research related to acute lung injury and intervertebral disc degeneration.

Ravagalimab (ABBV-323) is a CD40 antagonist (EC₅₀: 3.7 nM). Ravagalimab can be used for research of Crohn's disease.

Tecaginlimab (BNT-312) is a Fc-inert bispecific antibody for dual targeting and conditional stimulation of CD40 and 4-1BB. Tecaginlimab can enhance priming and reactivation of tumor-specific immunity.

Vitexin-4''-O-glucoside (4''-O-Glucosylvitexin) is an orally active natural flavonoid component with multiple pharmacological effects including antioxidation, anti-inflammation, cytoprotection and anti-apoptosis. Vitexin-4''-O-glucoside regulates the MAPK signaling pathway by downregulating the phosphorylation levels of JNK and p38, thereby blocking endoplasmic reticulum stress responses. Vitexin-4''-O-glucoside alleviates oxidative stress by reducing MDA content and upregulating the activities of SOD and CAT, attenuates inflammation by downregulating the expressions of inflammatory factors TNF-α, IL-1β and IL-6, and also reduces LDH release and inhibits caspase-3 activation. Vitexin-4''-O-glucoside effectively improves drug-induced acute liver injury and exerts significant protective effects against myocardial hypoxia/reoxygenation injury. Vitexin-4''-O-glucoside can be used in studies on acute liver injury, cardiovascular diseases and myocardial hypoxia-reoxygenation injury.

LZ-07 is a selective IRAK4 PROTAC degrader with DC₅₀ values of 1.14 nM (DOHH2) and 2.70 nM (TMD8). LZ-07 acts as a PI3Kδ kinase inhibitor with an IC₅₀ of 92 nM. By bridging IRAK4 and the CRBN E3 ubiquitin ligase, LZ-07 induces IRAK4 degradation via the ubiquitin-proteasome system, ablates both its kinase and scaffold functions, and thereby blocks downstream inflammatory signal transduction. LZ-07 can be used in research related to autoimmune diseases.

Hordenine hydrochloride (Ordenina hydrochloride; Peyocactine hydrochloride) is a multifunctional alkaloid with oral activity and blood-brain barrier penetration. Hordenine hydrochloride inhibits LPS-induced phosphorylation of p38, JNK, ERK1/2, p65, IκB, and AKT, prevents p65 nuclear translocation, and suppresses inflammatory cytokines and mediators. Hordenine hydrochloride promotes M2 macrophage polarization, restores blood-milk barrier integrity, alleviates oxidative stress by reducing ROS and MDA, and attenuates LPS-induced lung injury and pulmonary edema. Hordenine hydrochloride inhibits cAMP production, CREB phosphorylation, and MITF expression, thereby suppressing melanin synthesis in melanocytes and reconstructed epidermis. Hordenine hydrochloride activates the Wnt/β-catenin signaling pathway, promotes dermal papilla cell proliferation and hair shaft elongation, and accelerates hair regeneration. Hordenine hydrochloride activates DRD2, acts as a D3R partial agonist, α2A-AR full agonist, and 5-HT2A-R antagonist, and inhibits SERT and DAT. Hordenine hydrochloride inhibits α-synuclein accumulation and ameliorates motor deficits in Parkinson's disease models. Hordenine hydrochloride limits alcohol intake, reduces relapse drinking behavior, and modulates alcohol-induced conditioned place preference. Hordenine hydrochloride can be used for research on mastitis, skin pigmentation, acute lung injury, foodborne diseases, hair loss, Parkinson's disease, bacterial infections, and alcohol use disorder.

N-Desmethyl clomipramine-d₃ hydrochloride (Desmethylclomipramine-d₃ hydrochloride; Norclomipramine-d₃ hydrochloride) is the deuterated-labeled N-Desmethyl clomipramine hydrochloride (HY-12388A). N-Desmethyl clomipramine hydrochloride is the orally active major active metabolite of the tricyclic antidepressant Clomipramine (HY-B0457A), possessing multiple activities including anti-inflammatory, antioxidant, antibacterial, and antiparasitic effects. N-Desmethyl clomipramine hydrochloride blocks autophagosome-lysosome fusion, leading to the accumulation of LC3-II, p62, ATG7, WIPI2, and ATG5-12, reactivates the p53/p21 pathway, induces apoptosis through C-PARP and C-CAS3, and inhibits the proliferation, migration, and invasion of renal cancer cells. N-Desmethyl clomipramine hydrochloride inhibits LdTOPIA, inducing R-loop accumulation in the nucleus of Leishmania, ultimately causing parasite death. N-Desmethyl clomipramine hydrochloride can be used for research on depression, metastatic renal cell carcinoma, and leishmaniasis.

Anemonin (Pulsatilla camphor; Anemonine; trans-Anemonin) is a naturally occurring bislactone small molecule derived from Ranunculaceae with blood-brain barrier permeability, possessing a variety of activities including anti-inflammatory, antioxidant, neuroprotective, melanogenesis-inhibiting, and antiparasitic effects. Anemonin inhibits iNOS to reduce NO release; it inhibits PKC-θ protein expression and downregulates the pro-inflammatory factors TNF-α, IL-1β, and IL-6; it enhances the activities of the antioxidant enzymes SOD, CAT, and GSH-Px, and reduces MDA and ROS levels. Anemonin modulates the Bcl-2 / Bax / caspase-3 pathway to inhibit apoptosis; it downregulates melanogenesis-related molecules including MITF, TYR, TRP1, and TRP2, thereby inhibiting melanin synthesis in human melanocytes. Anemonin inhibits Leishmania and Schistosoma mansoni. Anemonin is used in research related to diseases such as hyperpigmentation, cerebral ischemia/reperfusion injury, inflammation, sepsis-induced acute lung injury, acute ulcerative colitis, leishmaniasis, and schistosomiasis.

Pentadecane-d₃₂ is the deuterium labeled Pentadecane (HY-N7926). Pentadecane is an orally active natural plant volatile alkane with anti-inflammatory, analgesic, antipyretic and anti-leishmanial activities. Pentadecane presents IC₅₀ values of 65.3 μM, 60.5 μM and 194.8 μM against Leishmania infantum promastigotes, amastigotes and intracellular amastigotes, respectively. Pentadecane downregulates the mRNA expression of TNF-α and IL-12 and inhibits the release of inflammatory mediators. Pentadecane arrests the cell cycle of Leishmania infantum and induces apoptosis. Pentadecane can be applied to the research of inflammation and leishmaniasis.

Aureusidin is a flavonoid compound that is isolated and extracted from Antirrhinum majus and exhibits oral activity. Aureusidin possesses antioxidant, neuroprotective, and anti-inflammatory properties. Aureusidin directly targets and binds MD2 and Caspase-3 with high affinity, synergistically inhibits the TLR4/NF-κB inflammatory pathway and GSDME-mediated pyroptosis, and activates the Nrf2/HO-1 antioxidant axis via the ROS/MAPKs pathway. Aureusidin is a bovine liver arginase inhibitor with an IC₅₀ of 57.1 µM. Aureusidin is used for research on inflammation-related diseases (osteoarthritis), acute liver injury, and endothelial dysfunction.