IRAK-1-4 Inhibitor I is an inhibitor of interleukin-1 receptor-associated kinase 1/4 (IRAK 1/4) with IC50s of 0.2 μM and 0.3 μM, respectively.
Pimecrolimus is an immunophilin ligand, which binds specifically to the cytosolic receptor, immunophilin macrophilin-12.Target: OthersPimecrolimus blocks T-lymphocyte activation pathway by inhibiting calcineurin function [1]. Pimecrolimus prevents the release of cytokines and pro-inflammatory mediators from mast cells. Pimecrolimus binds to macrophilin-12, the pimecrolimusmacrophilin complex then binds to the cytosolic enzyme calcineurin phosphatase. The pimecrolimus-macrophilin complex prevents the dephosphorylation of the cytoplasmic component of the nuclear factor of activated T cells by inhibiting the action of calcineurin. Pimecrolimus inhibits not only the transcription and synthesis of cytokines from mast cells, but also the release of preformed mediators serotonin and β-hexosaminidase by the inhibition of Fcε-RI-mediated degranulation and secretion. Pimecrolimus treatment causes a strong down-regulation of the expression of mRNA for genes associated with the macrolactam target pathway and inflammation [2].Pimecrolimus is found to be as effective as cyclosporine A following oral ingestion and slightly superior after subcutaneous administration in mice. Pimecrolimus contrasts cyclosporine A and tacrolimus by inhibiting ongoing secondary inflammatory response, but not impairing the primary immune response in allergic contact dermatitis in mice. [2] Pimecrolimus is as effective as the high-potency corticosteroid clobetasol-17-propionate in a pig model of allergic contact dermatitis (ACD). Pimecrolimus also effectively reduces skin inflammation and pruritus in hypomagnesemic hairless rats, a model that mimics acute signs of atopic dermatitis [3].
Prostaglandin D2 (PGD2) is one of the major PGs actively produced in the brain of various mammals[1]. Prostaglandin D2 is one of the most potent endogenous sleep promoting substances[2]. PGD2 plays a protective role by suppressing inflammation[3].
GsAF-1 is a peptide toxin containing three disulfide bonds. GsAF-1 can be isolated from the venom of the Chilean pink tarantula. GsAF-1 can be used for research of moderate-to-severe pain[1].
Yadanziolide B, a natural indole alkaloid, is a potential H5N1 neuraminidase inhibitor[1][2].
Dilmapimod (SB-681323) is a potent p38 MAPK inhibitor that potentially suppresses inflammation in chronic obstructive pulmonary disease.
GPR68-IN-1 is a potent GPR68 inhibitor with an EC50of 170 nM. GPR68-IN-1 is extracted from patent WO2020214896 (OGM1), and can be used for autoimmune chronic inflammatory diseases research[1].
Raddeanoside R17 (Pulchinenoside E3) is a saponins compound that can be isolated from the root of Pulsatilla koreana. Raddeanoside R17 shows anti-inflammatory effects[1][2].
Dithranol is highly effective in the treatment of psoriasis.Target: OthersDithranol accumulates in mitochondria where it interferes with the supply of energy to the cell, probably by the oxidation of dithranol releasing free radicals. This impedes DNA replication and so slows the excessive cell division that occurs in psoriatic plaques. In addition Dithranol may act by reducing the elevated levels of cGMP that occurs in psoriasis.
(3S,4S)-Tofacitinib is the S-enantiomer of Tofacitinib. Tofacitinib inhibits JAK3 with IC50 of 1 nM.
Sitravatinib malate (MGCD516 malate) is an orally bioavailable receptor tyrosine kinase (RTK) inhibitor with IC50s of 1.5 nM, 2 nM, 2 nM, 5 nM, 6 nM, 6 nM, 8 nM, 0.5 nM, 29 nM, 5 nM, and 9 nM for Axl, MER, VEGFR3, VEGFR2, VEGFR1, KIT, FLT3, DDR2, DDR1, TRKA, TRKB, respectively[1]. Sitravatinib malate shows potent single-agent antitumor efficacy and enhances the activity of PD-1 blockade through promoting an antitumor immune microenvironment[2].
ROCK-IN-32 is an effective Rho-kinase inhibitor.
Hemocyanin is a large copper-containing respiratory protein. Hemocyanin is an important non-specific innate immune defense molecule with phenoloxidase, antiviral, antibacterial, hemolytic, and antitumor activities[1].
Cendakimab (RPC4046; ABT 308; CC-93538) is a selective, humanized, recombinant monoclonal antibody against the IL-13 molecule. Cendakimab has a high affinity and potency for both human wild-type and variant IL-13 and blocks binding of IL-13 to both IL-13Rα1 and IL-13Rα2 with IC50s of 352 pM and 631 pM by ELISA, respectively. Cendakimab recognizes both wild-type human IL-13 and the common polymorphic variant R110Q, with binding affinities of 52 and 50 pM, respectively. Cendakimab has the potential for IL-13-related allergic/inflammatory diseases (e.g., asthma and eosinophilic esophagitis)[1].
P1788 is a dihydroorotate dehydrogenase (DHODH) inhibitor. P1788 induces DNA damage[1].
1-beta-D-Arabinofuranosyluracil (Uracil 1-β-D-arabinofuranoside) isolated from the Caribbean sponge Tectitethya crypta, is a methoxyadenosine derivative. 1-beta-D-Arabinofuranosyluracil has demonstrated a diverse bioactivity profile including anti-inflammatory activity, analgesic and vasodilation properties[1]. 1-beta-D-Arabinofuranosyluracil reduces a proliferation of mouse lymphoma cells[2].
CTX-471 is a fully human monoclonal antibody of CD137. CTX-471 has bind affinity for recombinant human, cynomolgus macaque CD137 and mouse CD137 with Kd values of 50 nM, 61 nM and 748 nM, respectively. CTX-471 can be used for the research of immunomodulation and cancer[1].
Sandaracopimaric acid is a diterpenoid with anti-inflammatory effect. Sandaracopimaric acid reduces the contraction of phenylephrine-induced pulmonary arteries with an EC50 of 43.93 μM[1][2].
Carbenoxolone, a semi-synthetic derivative of glycyrrhetinic acid, has previously been used for the management of dyspepsia and peptic ulcer because of its anti-inflammatory properties[3]. Carbenoxolone, a general hemichannel and gap junction inhibitor, has the therapeutic potential of carbenoxolone in the treatment of chronic liver disease[2]. Carbenoxolone is a suitable candidate for the inhibition of Aβ42 aggregation and the therapeutic potential of Cbx against AD[1]. Carbenoxolone is small molecule Pannexin1 (Panx1,is an ATP release channel) inhibitor, attenuate Panx1 channel activity through modulation of the first extracellular loop[4].Carbenoxolone is an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor that converts inactive glucocorticoid into an active form. Carbenoxolone has antiviral activity against DENV infection targeting the virus itself[6].
H4R antagonist 3 (Example 18) is a histamine-4 receptor antagonist with an EC50 of ＜10 mM. H4R antagonist 3 can be used for the research of prevention of inflammatory, autoimmune, allergic, and ocular diseases[1].
ERK1/2 inhibitor 6 is a potent inhibitor of ERK1/2. Mitogen-activated protein kinase (MAPK) plays an extremely important role in the signal transduction pathway, and extracellular signal regulated kinase (ERK) is a member of the MAPK family. ERK1/2 inhibitor 6 has the potential for the research or prevention of cancer, inflammation or other proliferative diseases (extracted from patent WO2021063335A1, compound 1)[1].
Asiatic acid, a pentacyclic triterpene found in Centella asiatica, induces apoptosis in melanoma cells. Asiatic acid can be used to treat skin cancer[1]. Asiatic acid also has anti-inflammatory activities[2].
Cisd2 agonist 2 (compound 6) is an orally active Cisd2 activator (EC50=191 nM), while the Cisd2 levels is correlated with nonalcoholic fatty liver disease (NAFLD). Cisd2 agonist 2 has no significant toxicity in vivo in Cisd2hKO-het mice (heterozygous hepatocyte-specific Cisd2 knockout)[1].
DAPT is a γ-secretase inhibitor with IC50s of 115 and 200 nM for total Aβ and Aβ42, respectively.
IFN alpha-IFNAR-IN-1 is a nonpeptidic, low-molecular-weight inhibitor of the interaction between IFN-α and IFNAR; inhibit MVA-induced IFN-α responses by BM-pDCs (IC50=2-8 uM).IC50 value:Target: IFN alpha-IFNAR interaction inhibitorIFN alpha-IFNAR-IN-1 specifically inhibits MVA-induced IFN-α responses by BM-pDCs. IFN alpha-IFNAR-IN-1 inhibited the IFN-α responses that were elicited after treatment with CpG2216, stimulation with poly(I:C), and infection with VSV-M2, whereas the total IL-12 production was notably less affected under those conditions. IFN alpha-IFNAR-IN-1 exerts immunosuppressive activity by the direct interaction with IFN-α [1].
Scopoletin is an inhibitor of acetylcholinesterase (AChE).
Rhododendrol can induce leukoderma. Rhododendrol induces generation of hydroxyl radicals and melanocyte cytotoxicity by increasing glutathione levels. Rhododendrol is a phenolic compound that can be isolated from plants such as Acer nikoense and Betula platyphylla[1].
JNK3 inhibitor-2 is a potent and selective JNK3 inhibitor with IC50 values of >100, >100, 0.25 µM for JNK1, JNK2, JNK3, respectively. JNK3 inhibitor-2 shows DDR1 and EGFR (T790M, L858R) inhibition[1].
LP99 is the first potent and selective BRD7/9 bromodomain inhibitor with Kd of 99 nM for BRD9; inhibits IL‐6 secretion from THP‐1 cells in a dose‐dependent manner; decreases BRET for both BRD7 and BRD9 in both the H3.3 and H4 systems in a dose‐dependent manner, with cellular IC50 values in the low micromolar range for both histones.
BAY 61-3606 is a potent, ATP-competitive, reversible, and highly selective inhibitor of Syk tyrosine kinase activity (Ki= 7.5 nM) with no inhibitory effect against Btk, Fyn, Itk, Lyn, and Src.IC50 value: 7.5 nM (Ki) [1]Target: Sykin vitro: BAY 61-3606 inhibited not only degranulation (IC50 values between 5 and 46 nM) but also lipid mediator and cytokine synthesis in mast cells. BAY 61-3606 was highly efficacious in basophils obtained from healthy human subjects (IC50 = 10 nM) and seems to be at least as potent in basophils obtained from atopic (high serum IgE) subjects (IC50 = 8.1 nM). B cell receptor activation and receptors for Fc portion of IgG signaling in eosinophils and monocytes were also potently suppressed by BAY 61-3606 [1]. We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF [2].in vivo: Oral administration of BAY 61-3606 to rats significantly suppressed antigen-induced passive cutaneous anaphylactic reaction, bronchoconstriction, and bronchial edema at 3 mg/kg. Furthermore, BAY 61-3606 attenuated antigen-induced airway inflammation in rats [1].