Immunology & Inflammation

L-156602 is a C5a receptor antagonist that inhibits inflammation and blocks the migration of monocytes and neutrophils to sites of infiltration in mouse inflammatory models. It also suppresses the efferent phase of delayed-type hypersensitivity (DTH).

Tarvicopan is an inhibitor for complement factor D.

Lanoracopan is a potent inhibitor of complement factor B, with an IC₅₀ of 1.2 μM. It is suitable for research in inflammation- and immunity-related diseases.

CP-289,503 is an inhibitor of the complement C5a receptor, with an IC₅₀ of 1 μM. The C5a receptor mediates pro-inflammatory signaling by binding to C5a, a complement activation product that stimulates leukocyte and phagocyte activation, upregulates integrins, and induces degranulation of inflammatory cells, contributing to endothelial damage. By blocking C5a signaling, CP-289,503 may be useful in the treatment of various inflammatory diseases.

DB0614 is a PROTAC molecule utilizing a cereblon ligand, designed as a selective and potent degrader of NEK9 and other kinases. It induces the degradation of multiple kinases, including ABL1, ABL2, BLK, CDK11B, CDK4, CSK, EPHA3, FER, GAK, LIMK1, MAP3K20, MAP4K1–3, MAP4K5, MAPK14, MAPK7–9, MAPKAPK2/3, NLK, PDIK1L, PTK2B, RIPK1, RPS6KA1/3, SIK2/3, STK35, TNK2, and ULK1. DB0614 is suitable for research involving diseases or disorders driven by aberrant kinase activity.

MY-1B is a covalent inhibitor of the RNA methyltransferase NSUN2 (IC50: 1.3 μM), stereoselectively targeting active-site cysteine residues (C271). It also covalently binds to PSME1, disrupting the proteasome regulatory complex and downregulating specific MHC-I subtype presentation.

MK-0159 is an orally active, potent, and selective inhibitor of CD38, with IC₅₀ values of 22 nM for human, 3 nM for mouse, and 70 nM for rat CD38. It exhibits good microsomal stability in both human and rodent liver microsomes. MK-0159 effectively increases NAD⁺ (nicotinamide adenine dinucleotide) levels and decreases ADPR (adenosine diphosphate ribose) concentrations in whole blood and heart tissue, making it a promising compound for research in metabolic, cardiovascular, and age-related diseases.

ADH-503 ((Z)-Leukadherin-1 choline) is an orally active, allosteric agonist of CD11b, an integrin subunit expressed on myeloid cells. By activating CD11b, ADH-503 promotes the repolarization of tumor-associated macrophages (TAMs) toward a pro-inflammatory phenotype, reduces the infiltration of immunosuppressive myeloid cells into tumors, and enhances dendritic cell responses. These immunomodulatory effects support its potential use in cancer immunotherapy.

JR14a is a potent thiophene-based antagonist of the human complement C3a receptor (C3aR). It exhibits high selectivity for C3aR over the C5a receptor and effectively suppresses C3aR-mediated inflammatory responses. JR14a is a valuable tool for studying the role of C3aR in immune regulation and inflammation-related diseases.

Phaseoloidin is a homogentisic acid glucoside isolated from *Nicotiana attenuata* trichomes. It plays a defensive role in the plant's resistance against lepidopteran herbivores by significantly reducing the growth of both specialist (*Manduca sexta*) and generalist (*Spodoptera littoralis*) larvae. In addition to its insect-deterrent properties, phaseoloidin also exhibits anti-complement activity, suggesting potential immunomodulatory applications.

Icotrokinra (JNJ-77242113) is an orally available and selective antagonist of the interleukin-23 (IL-23) receptor. It potently inhibits IL-23-induced STAT3 phosphorylation in peripheral blood mononuclear cells (IC₅₀ = 5.6 pM) and suppresses IL-23-induced interferon-γ (IFN-γ) production in natural killer (NK) cells (IC₅₀ = 18.4 pM). Icotrokinra also demonstrates anti-inflammatory activity in a rat TNBS-induced colitis model. It is a promising therapeutic candidate for the study and treatment of inflammatory conditions such as psoriasis, psoriatic arthritis, and inflammatory bowel disease (IBD).

Raleukin (AMG-719) is a recombinant, non-glycosylated human interleukin-1 receptor (IL-1R) antagonist. It functions by competitively inhibiting the binding of interleukin-1 (IL-1) to its receptor, thereby blocking IL-1–mediated pro-inflammatory signaling. As one of the first biological agents developed to inhibit IL-1 activity, Raleukin has potential applications in the treatment of inflammatory and autoimmune diseases.

Phenidone is an orally active dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX) pathways, exhibiting anti-inflammatory and immunomodulatory effects. It has been shown to ameliorate paralysis in rat models of experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis. Phenidone also acts as a potent hypotensive agent in spontaneously hypertensive rats. Additionally, it has a long-standing application as a photographic developer due to its redox properties.

Glafenine is a non-selective, non-steroidal anti-inflammatory drug (NSAID) that inhibits both COX-1 and COX-2 enzymes. It exerts anti-inflammatory, anti-proliferative, and anti-migratory effects by suppressing the arachidonic acid metabolic pathway, thereby reducing prostaglandin production. Additionally, glafenine induces cell cycle arrest in vascular smooth muscle cells and endothelial cells and decreases the synthesis of the extracellular matrix protein tenascin. It is utilized in research related to inflammatory disorders, vascular restenosis, and cystic fibrosis.

L-NMMA acetate (NG-monomethyl-L-arginine acetate) is a non-selective nitric oxide synthase (NOS) inhibitor that targets all three NOS isoforms: neuronal (nNOS/NOS1), endothelial (eNOS/NOS3), and inducible (iNOS/NOS2). It exhibits Ki values of approximately 0.18 µM for rat nNOS, 0.4 µM for human eNOS, and 6 µM for mouse iNOS, making it a valuable tool for studying nitric oxide–mediated physiological and pathological processes.

CU-T12-9 is a specific and potent agonist of the Toll-like receptor 1/2 (TLR1/2) heterodimer, with an EC₅₀ of 52.9 nM in the HEK-Blue hTLR2 SEAP assay. It selectively activates TLR1/2 without affecting TLR2/6 and stimulates both innate and adaptive immune responses. CU-T12-9 signals through the NF-κB pathway, leading to elevated expression of downstream effectors such as TNF-α, IL-10, and iNOS, making it a valuable tool for immunological and inflammatory research.

LMT-28 is an orally active and the first synthetic interleukin-6 (IL-6) inhibitor that acts by directly binding to gp130, a key signal-transducing component of the IL-6 receptor complex. It selectively inhibits IL-6-induced phosphorylation of STAT3, JAK2, and gp130, exhibiting low toxicity. LMT-28 is a promising compound for research into IL-6-mediated inflammatory and autoimmune diseases.

Dexketoprofen trometamol (Dexketoprofen tromethamine salt) is an orally active, non-selective cyclooxygenase (COX) inhibitor. It exhibits analgesic, anti-inflammatory, and anti-cancer effects. As the active enantiomer of ketoprofen, Dexketoprofen trometamol is commonly used for the management of pain and inflammation, and it is also under investigation for its potential anticancer properties.

SC-58125 is a potent and selective cyclooxygenase-2 (COX-2) inhibitor with an IC50 of 0.04 μM. It demonstrates antitumor activity both in vitro and in vivo and is effective in reducing inflammation-related edema. Additionally, SC-58125 possesses analgesic properties, making it a valuable compound for research in cancer, inflammation, and pain management.

Balixafortide (POL6326) is a potent, selective, and well-tolerated peptidic antagonist of the CXCR4 receptor, with IC50 values below 10 nM. It demonstrates over 1000-fold selectivity for CXCR4 compared to other receptors, including CXCR7. Balixafortide effectively blocks β-arrestin recruitment and calcium flux, and is a strong mobilizer of hematopoietic stem and progenitor cells (HSPCs). It also exhibits anti-cancer activity, making it a promising candidate for oncology and hematology research.

Ladarixin (DF 2156A free base) is an orally active, allosteric, non-competitive antagonist of the chemokine receptors CXCR1 and CXCR2. By blocking these receptors, Ladarixin inhibits neutrophil recruitment and inflammatory responses. It is under investigation for the treatment of inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD) and asthma.

LIT-927 is a locally and orally active CXCL12 neutraligand with anti-inflammatory properties. It binds to CXCL12 with a Ki of 267 nM, thereby preventing its interaction with the CXCR4 receptor. LIT-927 is a valuable tool for studying CXCL12/CXCR4-mediated signaling in inflammatory and immune-related conditions.

Tin protoporphyrin IX dichloride (SnPPIX) is a potent inhibitor of heme oxygenase-1 (HO-1), an enzyme involved in cellular stress responses and tumor progression. SnPPIX has been shown to sensitize pancreatic ductal adenocarcinoma (PDAC) tumors to chemotherapy in mouse models, enhancing therapeutic efficacy and supporting its potential use as a chemosensitizing agent in cancer treatment.

TAT-14 is a 14-mer peptide that functions as a Nrf2 activator with anti-inflammatory properties. It does not alter Nrf2 mRNA expression but increases Nrf2 protein levels by targeting the Nrf2 binding site on Keap1, thereby stabilizing Nrf2 and promoting its activation.

Lobeglitazone sulfate is a novel thiazolidinedione and an orally active agonist of peroxisome proliferator-activated receptors (PPARs), with EC50 values of 137.4 nM for PPARγ and 546.3 nM for PPARα. It also acts as an inhibitor of the ERK/JNK/Smad/NF-κB signaling pathways. Lobeglitazone sulfate exhibits anti-inflammatory, anti-diabetic, anti-fibrotic, and anti-atherosclerotic activities, supporting its potential in the treatment of metabolic and inflammatory diseases.

6-Demethoxytangeretin is a flavonoid compound isolated from *Citrus reticulata* with demonstrated anti-inflammatory and anti-allergic properties. It inhibits IL-6 production and the expression of related genes in human mast cells by modulating the ALK and MAPK signaling pathways. Additionally, 6-Demethoxytangeretin enhances CRE-mediated transcription in hippocampal neurons, indicating potential neuroregulatory effects.

ERAS-0015 (Pan-RAS-IN-2) is a molecular glue that targets RAS by promoting the formation of ternary complexes with cyclophilin A (CYPA) and active RAS (ON) proteins. This interaction disrupts the binding of RAF to RAS, thereby inhibiting downstream signaling. Pan-rasin-2 exhibits significant antiproliferative activity in RAS-mutant cell lines and shows promise as an anti-tumor agent.

HKB99 is an allosteric inhibitor of phosphoglycerate mutase 1 (PGAM1) that induces apoptosis and suppresses cell migration by inhibiting the formation of invasive pseudopodia. It increases oxidative stress, activates the JNK/c-Jun pathway, and downregulates AKT and ERK signaling. HKB99 is a promising compound for the study of non-small cell lung cancer (NSCLC).

7-Hydroxyflavone is an orally active flavonoid isolated from *Clerodendrum phlomidis*, exhibiting notable anti-inflammatory activity. It protects renal cells from nicotine-induced cytotoxicity through activation of the ERK/Nrf2/HO-1 signaling pathway. Additionally, 7-Hydroxyflavone inhibits PKM2 with an IC50 of 2.12 μM, and suppresses COX-2 and 5-LOX with IC50 values of 27 μg/mL and 33 μg/mL, respectively.

Iruplinalkib (WX-0593) is an orally active and selective ALK/ROS1 inhibitor that effectively blocks tyrosine autophosphorylation of ALK, mutant ALK, and EGFR, with IC50 values ranging from 5.38 to 16.74 nM. Additionally, it inhibits the transport activity of MATE1, MATE2K, P-gp, and BCRP. Iruplinalkib is under investigation for the treatment of non-small cell lung cancer (NSCLC).

α-Amyrin is an orally active pentacyclic triterpenoid that activates the ERK and GSK-3β signaling pathways. It is studied for its potential in treating metabolic syndrome induced by a high-fructose diet and cognitive dysfunction associated with reduced cholinergic neurotransmission.

Gondoic acid (cis-11-Eicosenoic acid) is a monounsaturated long-chain fatty acid found in various plant oils and nuts. It exhibits anti-inflammatory activity by reducing reactive oxygen species (ROS) production and inhibiting the PKCθ/ERK/STAT3 signaling pathway. Gondoic acid is also utilized as a raw material in medical applications and as a moisturizing agent in cosmetic formulations.

Tauroursodeoxycholate (Tauroursodeoxycholic acid; TDUCA) dihydrate is an inhibitor of endoplasmic reticulum (ER) stress that significantly downregulates pro-apoptotic molecules, including caspase-3 and caspase-12. Additionally, it suppresses ERK signaling, contributing to its cytoprotective and anti-apoptotic effects.

RMC-4998 is an orally active inhibitor that selectively targets the active, GTP-bound state of the KRAS^G12C mutant. It forms a ternary complex with intracellular cyclophilin A (CYPA) and activated KRAS^G12C, exhibiting an IC50 of 28 nM. RMC-4998 suppresses ERK signaling and induces apoptosis in KRAS^G12C-mutant cancer cells, making it a valuable candidate for tumor research.

Fenoprofen (LILLY-53858) is a nonsteroidal anti-inflammatory drug (NSAID) that functions primarily by inhibiting cyclooxygenase (COX) enzymes, thereby reducing the synthesis of pro-inflammatory prostaglandins. In addition to its classical NSAID activity, Fenoprofen has been identified as a positive allosteric modulator (PAM) of melanocortin receptors (MCRs), enhancing MCR-mediated signaling. Fenoprofen also promotes ERK1/2 activation in HEK293T cells, suggesting additional modulation of intracellular signaling pathways involved in inflammation and cellular proliferation.

ACA-28 (compound 2a) is a potent modulator of the ERK MAPK signaling pathway that exerts anticancer effects through a unique mechanism involving ERK hyperactivation. Rather than inhibiting ERK activity directly, ACA-28 induces sustained ERK activation, which paradoxically triggers apoptosis in cancer cells. It demonstrates selective cytotoxicity, inhibiting the growth of melanoma cells (SK-MEL-28) with an IC₅₀ of 5.3 μM, while showing lower toxicity toward normal human melanocytes (NHEM), with an IC₅₀ of 10.1 μM. ACA-28's ability to exploit ERK signaling dysregulation for selective induction of apoptosis makes it a promising candidate for further development in cancer therapy, particularly in ERK-dependent malignancies.

Cearoin is a bioactive compound that promotes both autophagy and apoptosis by inducing reactive oxygen species (ROS) production and activating the ERK signaling pathway. Through this dual mechanism, cearoin contributes to the regulation of cellular stress responses and programmed cell death. Its ability to modulate these processes makes it a valuable candidate for research in cancer biology and other diseases involving dysregulated autophagy or apoptosis.

NVP-DFV890 (Compound 102) is a selective NLRP3 inhibitor that antagonizes NLRP3 inflammasome activity. It is a valuable tool for investigating therapeutic approaches in osteoarthritis research.

Lobeglitazone is a novel thiazolidinedione-class compound and an orally active dual agonist of peroxisome proliferator-activated receptors (PPARs), with EC₅₀ values of 137.4 nM for PPARγ and 546.3 nM for PPARα. In addition to its metabolic effects, Lobeglitazone functions as an inhibitor of multiple pro-inflammatory and pro-fibrotic signaling pathways, including ERK, JNK, Smad, and NF-κB. Lobeglitazone exhibits a broad range of pharmacological activities, including anti-inflammatory, anti-diabetic, anti-fibrotic, and anti-atherosclerotic effects. These properties make it a promising candidate for therapeutic research in metabolic syndrome, type 2 diabetes, cardiovascular disease, and fibrosis-related conditions.

Anti-inflammatory agent 35 (compound 5a27) is an orally active curcumin analogue that exhibits potent anti-inflammatory activity. It exerts its effects by blocking mitogen-activated protein kinase (MAPK) signaling and inhibiting the nuclear translocation of the NF-κB subunit p65, thereby suppressing key inflammatory pathways. Additionally, compound 5a27 reduces neutrophil infiltration and the production of pro-inflammatory cytokines. In vivo, it significantly attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI), highlighting its potential as a therapeutic candidate for inflammatory and respiratory disorders.

RBN013209 is an orally active, small molecule inhibitor of CD38, exhibiting potent inhibitory activity with an IC₅₀ ranging from 0.01 to 0.1 μM against human CD38. It effectively blocks the enzymatic conversion of extracellular NAD⁺ to ADPR and cADPR in both tumor cells and peripheral blood mononuclear cells (PBMCs), thereby modulating the tumor microenvironment. Beyond its direct antitumor potential, RBN013209 also enhances the efficacy of immunotherapies. It preserves the naïve and central memory phenotypes of CAR-T cells, while reducing the expression of activation markers and exhaustion-associated inhibitory receptors. These properties position RBN013209 as a promising agent for both tumor research and the development of combination strategies to improve CAR-T cell persistence and function.

RMC-7977 is an orally bioavailable, triple-complex RAS inhibitor that functions by simultaneously binding to cyclophilin A (CypA; K_d = 195 nM) and KRAS^G12V (K_d = 292 μM), facilitating the formation of a stable inhibitory complex. It exhibits broad-spectrum activity against RAS isoforms—including KRAS, NRAS, and HRAS—across both wild-type and mutant variants. RMC-7977 suppresses key oncogenic signaling pathways by inhibiting the phosphorylation of ERK, CRAF, and RSK, while promoting apoptosis through enhanced PARP cleavage. This dual mechanism results in significant tumor regression and reduced acquired resistance in KRAS^G12C-driven cancer models. It also shows favorable tolerability across a range of RAS-mutant tumor models, positioning it as a promising therapeutic candidate for RAS-driven malignancies.

Elironrasib is an orally active, covalent inhibitor specifically targeting the active GTP-bound form of KRAS^G12C (KRAS^G12C(ON)). It uniquely functions by forming a stable tri-complex with KRAS^G12C(ON) and cyclophilin A (CypA) within tumor cells, leading to steric hindrance that blocks the interaction between KRAS and its downstream effectors. This mechanism effectively suppresses RAS-mediated signaling, particularly the ERK pathway. Elironrasib induces apoptosis in KRAS^G12C-mutant H358 non-small cell lung cancer cells and demonstrates potent antiproliferative activity across KRAS^G12C-mutant cell lines, with a median IC₅₀ of 0.11 nM. Its high specificity and novel mechanism make it a promising therapeutic candidate for cancers driven by KRAS^G12C mutations.

Lysophosphatidylcholines (LPCs) are orally active lysolipids and key components of oxidized low-density lipoprotein (oxLDL). They are bioactive molecules known to induce cellular injury, promote the production of pro-inflammatory cytokines such as interleukin-1β (IL-1β), and trigger apoptosis. LPCs play a significant role in the pathophysiology of various inflammatory conditions and have been implicated in the progression of sepsis by amplifying inflammatory responses. Due to these properties, LPCs are actively studied in the context of inflammation, cardiovascular disease, and sepsis-related research.

Anti-inflammatory agent 70 (N-Me-SP23) is a PROTAC-based degrader targeting the STING (stimulator of interferon genes) protein, a key regulator of innate immune and inflammatory responses. By promoting STING degradation, N-Me-SP23 effectively inhibits the STING signaling pathway, leading to reduced downstream inflammatory cytokine production. This compound exhibits notable anti-inflammatory activity and holds potential for therapeutic research in STING-associated autoimmune and inflammatory disorders.

Gnetol is a bioactive phenolic compound isolated from the root of *Gnetum montanum* with diverse pharmacological properties. It potently inhibits cyclooxygenase-1 (COX-1) with an IC₅₀ of 0.78 μM and exhibits histone deacetylase (HDAC) inhibitory activity. Gnetol is also a strong tyrosinase inhibitor, with an IC₅₀ of 4.5 μM against murine tyrosinase, leading to suppression of melanin biosynthesis. In addition to its antioxidant, antiproliferative, anticancer, and hepatoprotective effects, Gnetol modulates metabolic enzymes in a concentration-dependent manner, including α-amylase, α-glucosidase, and adipogenesis pathways, making it a promising candidate for research in oncology, dermatology, and metabolic disorders.

Licochalcone D is a naturally occurring flavonoid primarily found in the root of *Glycyrrhiza uralensis* (Chinese licorice). It functions as a potent and orally active inhibitor of the NF-κB p65 subunit, a key regulator of inflammation and cancer-related signaling pathways. Licochalcone D exhibits broad pharmacological properties, including antioxidant, anti-inflammatory, and anticancer activities, making it a promising candidate for research in inflammation-related diseases and oncology.

FPFT-2216 is a “molecular glue” degrader that facilitates the proteasomal degradation of multiple target proteins, including phosphodiesterase 6D (PDE6D), zinc finger transcription factors Ikaros (IKZF1) and Aiolos (IKZF3), as well as casein kinase 1α (CK1α). By promoting selective ubiquitination through E3 ligase recruitment, FPFT-2216 modulates key regulatory pathways and holds promise for research in oncology and inflammatory diseases.

PROTAC NCOA4 Degrader-1 (Compound V3) is a highly potent PROTAC targeting NCOA4, with a DC₅₀ of 3 nM in HeLa cells. It functions as a ferroptosis inhibitor by reducing NCOA4 levels and lowering intracellular ferrous iron (Fe²⁺) concentrations. PROTAC NCOA4 Degrader-1 has demonstrated protective effects in a CCl₄-induced acute liver injury model, making it a valuable tool for studying ferroptosis and liver disease therapeutics.

AZD2098 is a potent and selective CCR4 inhibitor with pIC₅₀ values of 7.8–8.0 across human, rat, mouse, and dog. It is commonly used in asthma research to study CCR4-mediated inflammatory pathways.