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Neuronal-Immune Signaling Shapes Cancer Immunity

Tumor Microenvironment Cancer Immunotherapy Intercellular Communication & Diseases

Neuronal-immune signaling shapes cancer immunity by linking nerves, malignant cells, and immune cells inside the tumor microenvironment. Cancer neuro-immunity has moved from an overlooked observation of tumor innervation to a high-interest field because recent studies show that peripheral nerves release neuromodulatory factors, regulate antitumor immunity, and create targetable immune-suppressive circuits. Tumor innervation, sympathetic signaling, sensory neurons, and neuropeptides now define a mechanistic layer of cancer immunity beyond tumor cells, stromal cells, and immune checkpoints[1][2][3].

Mechanistically, sympathetic norepinephrine, sensory neuropeptides, acetylcholine pathways, and tumor-induced nerve injury alter immune recruitment and function. Sensory neurons can attract myeloid-derived suppressor cells in melanoma, restrict tertiary lymphoid structure formation, and release CGRP to suppress tumor-infiltrating lymphocytes in head and neck cancer. In oral squamous cell carcinoma, lingual denervation reduced TGFβ signaling, lowered PD-L1 expression, enhanced CD8+ T-cell activity, and improved anti-PD-1 efficacy[4][5][6][7].

Disease applications center on immunotherapy resistance, neural-targeted combination therapy, and tumor microenvironment remodeling. Cancer-induced nerve injury promotes anti-PD-1 resistance through myelin degradation, IL-6 and type I interferon inflammation, immune suppression, and exhaustion, while blockade of the injury-associated inflammatory axis can restore antitumor immunity. A lung tumor-brain circuit also uses Npy2r-expressing vagal sensory nerves and sympathetic β2-adrenergic signaling in alveolar macrophages to restrain cancer immunity, showing that future therapy may need to target local nerves, systemic neural circuits, and immune checkpoints together[8][9].

Research gaps include defining which tumors depend on sensory, sympathetic, or parasympathetic signaling; standardizing nerve-density and neuroimmune biomarkers; and testing whether denervation, β-adrenergic blockade, CGRP inhibition, TGFβ inhibition, IL-6 blockade, or circuit-level neuromodulation can safely improve immunotherapy. The strongest prospect is not treating nerves as passive bystanders, but mapping neuronal-immune signaling as a druggable regulator of the cancer-immunity cycle[1][3][6][7][8][9].

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Cat. No. Product Name Information Application Publication
HY-13418 Dorsomorphin dihydrochloride
Dorsomorphin (Compound C) dihydrochloride is a potent, selective and ATP-competitive AMPK inhibitor, with a Ki of 109 nM. Dorsomorphin dihydrochloride inhibits BMP pathway by targeting the type I receptors ALK2, ALK3, and ALK6. Dorsomorphin dihydrochloride can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).
Organoid   AMPK   TGF-β Receptor   Autophagy  
Colorectal Cancer   Prostate Cancer   Ovarian Cancer   Pain   Digestive System Inflammation   Obesity  
823
HY-13418A Dorsomorphin
Dorsomorphin (BML-275) is a selective and ATP-competitive AMPK inhibitor (Ki=109 nM in the absence of AMP). Dorsomorphin (BML-275) selectively inhibits BMP type I receptors ALK2, ALK3, and ALK6. Dorsomorphin can reverse autophagy activation and anti-inflammatory effect of Urolithin A (HY-100599).
Organoid   AMPK   TGF-β Receptor   Autophagy  
823
HY-10431 SB-431542
SB-431542 is a TGF-β receptor kinase inhibitor (TRKI). SB-431542 has inhibitory activity for ALK4, ALK5 and ALK7 with IC50 values of 1 μM, 0.75 μM and 2 μM, respectively. SB-431542 also inhibits TGF-β-induced transcription, gene expression, apoptosis, and growth suppression. SB-431542 can be used for the research of cancer and signal transduction pathways.
Organoid   TGF-β Receptor   Apoptosis  
Colorectal Cancer   Prostate Cancer   Pancreatic Cancer   Digestive System Inflammation   Obesity   Lung Fibrosis  
324
HY-100941 CCCP
CCCP is an oxidative phosphorylation (OXPHOS) uncoupler. CCCP induces activation of PINK1 leading to Parkin Ser65 phosphorylation.
PINK1/Parkin   Oxidative Phosphorylation   STING   IFNAR   Mitochondrial Metabolism   Bacterial   Apoptosis  
Non-Small Cell Lung Cancer   Mycobacterium Tuberculosis Infection   Parkinson's Disease  
193
HY-10432 A 83-01
A 83-01 is a potent inhibitor of TGF-β type I receptor ALK5 kinase, type I nodal receptor ALK4 and type I nodal receptor ALK7, with IC50s of 12 nM, 45 nM and 7.5 nM against the transcription induced by ALK5, ALK4 and ALK7, respectively.
Organoid   TGF-β Receptor  
Cancer  
143
HY-13013 SIS3
SIS3 is a potent and selective inhibitor of Smad3 with an IC50 of 3 μM for Smad3 phosphorylation. SIS3 inhibits the myofibroblast differentiation of fibroblasts by TGF-β1.
TGF-beta/Smad  
Inflammation or Immune System Disease   Colorectal Cancer   Prostate Cancer   Lung Fibrosis  
113
HY-B0673 Pirfenidone
Pirfenidone (AMR69) is an antifibrotic agent that attenuates CCL2 and CCL12 production in fibrocyte cells. Pirfenidone has growth-inhibitory effect and reduces TGF-β2 protein levels in human glioma cell lines. Pirfenidone also has anti-inflammatory activities.
TGF-beta/Smad   CCR  
Colorectal Cancer   Prostate Cancer   Viral Infection   Digestive System Inflammation   SARS-CoV-2 Infection   Lung Fibrosis   Rheumatoid Arthritis  
97
HY-12071 LDN193189
LDN193189 (DM-3189) is a potent selective BMP type I receptor (BMP I) inhibitor. LDN193189 efficiently inhibits transcriptional activity of the BMP type I receptors ALK2 and ALK3 with IC50 values of 5 nM and 30 nM, respectively. LDN193189 can be used for the research of bone morphogenetic protein signalling, such as fibrodysplasia ossificans progressiva.
Organoid   TGF-β Receptor  
Breast Cancer  
95
HY-10964 Vadimezan
Vadimezan (DMXAA), the tumor vascular disrupting agent (tumor-VDA), is a murine agonist of the stimulator of interferon genes (STING) and also a potent inducer of type I IFNs and other cytokines. Vadimezan is unable to activate human STING. Vadimezan has anti-influenza virus H1N1-PR8 activities.
STING   IFNAR   Influenza Virus  
Prostate Cancer   Viral Infection   Autoimmune Disease   Non-Small Cell Lung Cancer  
81
HY-16141 Cilengitide
Cilengitide (EMD 121974) is an integrin (integrin) inhibitor with blood-brain barrier permeability, with IC50 values against human targets as follows: 0.61 nM for αvβ3, 8.4 nM for αvβ5, 14.9 nM for α5β1, 5400 nM for αIIbβ3, 2050 nM for αvβ6, 2350 nM for αvβ8. Cilengitide inhibits the binding of integrins to vitronectin, fibronectin, fibrinogen and LAP (TGF-β), and serves as an internal standard for solid-phase integrin binding assays. Cilengitide inhibits tumor cell viability, induces apoptosis, reduces the phosphorylation levels of STAT3, AKT and mTOR, downregulates the expression of PD-L1, inhibits cell viability and angiogenesis, regulates anti-tumor immune responses and slows tumor growth. Cilengitide can be used in research related to glioblastoma, melanoma, advanced solid tumors and refractory brain tumors.
Integrin   TGF-β Receptor   Apoptosis   PD-1/PD-L1   STAT   Akt   mTOR  
Melanoma   Glioblastoma  
75
HY-13226 Galunisertib
Galunisertib (LY2157299) is an oral and selective TGF-β receptor type I (TGF-βRI) kinase inhibitor with an IC50 of 56 nM.
TGF-β Receptor  
Lung Cancer   Breast Cancer   Colorectal Cancer   Prostate Cancer   Pancreatic Cancer   SARS-CoV-2 Infection   Obesity   Lung Fibrosis  
75
HY-100347A SRI-011381 hydrochloride
SRI-011381 hydrochloride is an orally active TGF-β signaling agonist, exhibits neuroprotective effects, with blood-brain barrier permeability.
TGF-beta/Smad  
Neurological, Eye or Ear Disease   Liver Cancer  
61
HY-100347 SRI-011381
SRI-011381 is an orally active TGF-β signaling agonist, exhibits neuroprotective effects.
TGF-beta/Smad  
Neurological, Eye or Ear Disease   Liver Cancer  
61
HY-100564A 2',3'-cGAMP sodium
2',3'-cGAMP sodium (2'-3'-cyclic GMP-AMP sodium) is a endogenous cGAMP in mammalian cells. 2',3'-cGAMP sodium binds to STING with a high affinity and is a potent inducer of interferon-β (IFNβ). 2',3'-cGAMP sodium is produced in mammalian cells in response to DNA in the cytoplasm.
Endogenous Metabolite   STING   IFNAR  
Metabolic or Endocrine Disease  
44
HY-100564 2',3'-cGAMP
2',3'-cGAMP (2'-3'-cyclic GMP-AMP) is a endogenous cGAMP in mammalian cells. 2',3'-cGAMP binds to STING with a high affinity and is a potent inducer of interferon-β (IFNβ). 2',3'-cGAMP is produced in mammalian cells in response to DNA in the cytoplasm.
Endogenous Metabolite   STING   IFNAR  
Metabolic or Endocrine Disease  
44
HY-117287 Deucravacitinib
Deucravacitinib (BMS-986165) is an orally active allosteric inhibitor of tyrosine kinase 2 (TYK2), with an IC50 of 0.2 nM and a Ki of 0.02 nM against the JH2 domain of TYK2, and it exhibits selectivity over other JAK subtypes and most of the kinome. Deucravacitinib blocks IL-23, IL-12, p-STAT1/3 and Type I IFN signaling, and inhibits Th17/Th1-mediated psoriasis inflammation. Deucravacitinib can be used in research related to moderate-to-severe plaque psoriasis, inflammatory bowel disease and systemic lupus erythematosus.
JAK   STAT   Interleukin Related   IFNAR  
Systemic Lupus Erythematosus   Psoriasis   Inflammatory Bowel Disease  
36
HY-16268 Kartogenin
Kartogenin (KGN) is an inducer of chondrogenic tissue formation (EC50: 100 nM). Kartogenin induces chondrogenesis by binding to fibrin A, disrupting its interaction with the transcription factor core binding factor beta subunit (CBFβ), and by modulating the CBFβ-RUNX1 transcriptional program. Kartogenin also promotes tendon-bone junction (TBJ) wound healing by stimulating collagen synthesis. Kartogenin is widely used in cell-free therapy in the field of regeneration for cartilage regeneration and protection, tendon-bone healing, wound healing and limb development. Kartogenin promotes cartilage repair, coordinates limb development, and is also used in osteoarthritis (OA) research.
TGF-beta/Smad  
Inflammation or Immune System Disease   Liver Cancer  
33
HY-13012 RepSox
RepSox (E-616452) is a potent and selective transforming growth factor-beta receptor I/activin like kinase 5 (TGF-β-RI/ALK5) inhibitor. RepSox inhibits ALK5 autophosphorylation with an IC50 value of 4 nM. RepSox can be used for the research of obesity and associated metabolic diseases such as type 2 diabetes.
Organoid   TGF-β Receptor  
Colorectal Cancer   Prostate Cancer   Pancreatic Cancer   Glucose Metabolism   Obesity   Lung Fibrosis  
23
HY-N1584 Halofuginone
Halofuginone (RU-19110), a Febrifugine derivative, is a competitive prolyl-tRNA synthetase inhibitor with a Ki of 18.3 nM. Halofuginone is a specific inhibitor of type-I collagen synthesis and attenuates osteoarthritis (OA) by inhibition of TGF-β activity. Halofuginone is also a potent pulmonary vasodilator by activating Kv channels and blocking voltage-gated, receptor-operated and store-operated Ca2+ channels. Halofuginone has anti-malaria, anti-inflammatory, anti-cancer, anti-fibrosis effects.
DNA/RNA Synthesis   TGF-beta/Smad   Parasite   Sodium Channel   Calcium Channel  
Inflammation or Immune System Disease   Ovarian Cancer   Parasitic Infection   Pulmonary Hypertension  
22
HY-N0439 Asiaticoside
Asiaticoside, a trisaccaride triterpene from Centella asiatica, suppresses TGF-β/Smad signaling through inducing Smad7 and inhibiting TGF-βRI and TGF-βRII in keloid fibroblasts; Asiaticoside shows antioxidant, anti-inflammatory, and anti-ulcer properties.
p38 MAPK   TGF-beta/Smad   Reactive Oxygen Species (ROS)   Apoptosis   Endogenous Metabolite  
Digestive System Disease   Lung Cancer   Neurodegenerative Disease   Pain   Digestive System Inflammation   Cardiovascular Disease  
19
HY-134581 Enpatoran
Enpatoran (M5049) is an orally active and selective TLR7/8 antagonist. Enpatoran inhibits the activation of the downstream type I interferon pathway. Enpatoran is used in studies of cutaneous lupus erythematosus, systemic lupus erythematosus with cutaneous manifestations, and psoriasis.
Toll-like Receptor (TLR)   IFNAR  
Systemic Lupus Erythematosus   Psoriasis  
18
HY-12273 DMH-1
DMH-1 is a selective BMP inhibitor. DMH-1 upregulates the expression of SOX1. DMH-1 increases cardiomyocyte progenitor cells and promotes the differentiation of mouse embryonic stem cells into cardiomyocytes. DMH-1 induces the differentiation of hiPSC-derived neural progenitor cells into β3-tubulin-positive neurons.
TGF-β Receptor   Organoid   Microtubule/Tubulin  
Neurological, Eye or Ear Disease   Heart Disease  
15
HY-116084 Trimethylamine N-oxide
Trimethylamine N-oxide is a gut microbe-dependent metabolite of dietary choline and other trimethylamine-containing nutrients. Trimethylamine N-oxide induces inflammation by activating the ROS/NLRP3 inflammasome. Trimethylamine N-oxide also accelerates fibroblast-myofibroblast differentiation and induces cardiac fibrosis by activating the TGF-β/smad2 signaling pathway.

Source: Host intestinal bacteria

Drug Metabolite   NOD-like Receptor (NLR)   Reactive Oxygen Species (ROS)   TGF-beta/Smad   Endogenous Metabolite  
Liver Cancer   Depression   Autoimmune Disease   Cardiovascular Disease  
12
HY-W250978 Ovalbumins
Ovalbumins are the major proteins in egg white. Ovalbumins act as an allergen and inducer, and can be applied to mouse models of allergic diseases. Ovalbumins can induce allergic rhinitis in mice via sensitization and nasal challenge. Ovalbumins can be used to establish asthma models.
Ovalbumin, low endotoxin (HY-W250978A) is recommended for model establishment.
Interleukin Related   IFNAR  
Allergic Asthma   Allergic Rhinitis  
7
HY-147124 RIG012
RIG012 is a potent RIG-I inhibitor with an IC50 of 0.71 μM using the NADH-coupled ATPase assay. RIG012 inhibits IFN-β and ISG hRsad2 expression.
IFNAR  
Cancer   Infection  
6
HY-P99168 Anifrolumab
Anifrolumab is a type I interferon (IFN) receptor antagonist, a human monoclonal antibody. Anifrolumab blocks the activity of type I interferon. Anifrolumab can be used in systemic lupus erythematosus (SLE) research.

Species: Human

IFNAR  
Systemic Lupus Erythematosus   Rheumatoid Arthritis  
5
HY-P99241 Ponsegromab
Ponsegromab is a Growth differentiation factor 15 (GDF15) inhibitor with human, cynomolgus monkey, and mouse target IC50 values of 0.123 nM, 0.053 nM, and 0.102 nM, respectively. Ponsegromab acts as a chemosensitizer, increases intracellular reactive oxygen species, reduces glutathione levels. Ponsegromab can be used for the research of oxaliplatin-resistant colorectal cancer.

Species: Human

TGF-beta/Smad   TGF-β Receptor  
Breast Cancer   Non-Small Cell Lung Cancer  
3
HY-P99355 Bimagrumab
Bimagrumab (Anti-ACVR2B Reference Antibody) is a human monoclonal antibody that blocks activin type II receptor (ActRII), with KDs of 1.7 pM and 434 pM for human ActRIIB and ActRIIA, respectively. Bimagrumab can be used for the research of pathological muscle loss and weakness.

Species: Human

TGF-β Receptor  
Metabolic or Endocrine Disease  
3
HY-W016562 Hippuric acid
Hippuric Acid is an orally active metabolite. Hippuric Acid can be produced by intestinal microorganisms from the metabolism of polyphenols, benzoic acid. Hippuric Acid decreases NRF2, MMP9 and leads to ROS accumulation. Hippuric Acid activates TGFβ/SMAD signaling. Hippuric Acid improves hyperuricemia and colitis. Hippuric Acid can also be used in cardiovascular disease research. .
Endogenous Metabolite   Keap1-Nrf2   MMP   Reactive Oxygen Species (ROS)   TGF-beta/Smad  
Colorectal Cancer   Cardiovascular Disease   Colitis   Hyperuricemia   Rheumatoid Arthritis  
2
HY-P10587 Icotrokinra
Icotrokinra (JNJ-77242113) is an orally available, selective antagonist of the IL-23 receptor. Icotrokinra inhibits IL-23-induced STAT3 phosphorylation in peripheral blood mononuclear cells (IC50=5.6 pM) and inhibits IL-23-induced interferon IFN-γ production in NK cells with an IC50 of 18.4 pM. Icotrokinra exhibits anti-inflammatory activity in a rat TNBS-induced colitis model. Icotrokinra can be used in the study of psoriasis, psoriatic arthritis, and inflammatory bowel disease.
Interleukin Related   STAT   IFNAR  
Inflammation or Immune System Disease  
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Keywords

neuronal-immune signaling, cancer immunity, neuroimmune crosstalk, tumor microenvironment, tumor innervation, sensory neurons, sympathetic signaling, CGRP, anti-PD-1 resistance