thp-1

Lsd1-in-20 is a potent dual inhibitor of LSD1/G9a with Ki values of 0.44 and 0.68 μM, respectively. LSD1-IN-20 showed antiproliferative activity against THP-1 leukemia cells and MDA-MB-231 breast cancer cells in vitro, with IC50 of 0.51 and 1.60 μM, respectively, at 72 h.

MLN-3897 TFA is a potent CCR1 antagonist that inhibits the binding of 125I-MIP-1α to THP-1 cell membranes.

GSK2983559 free acid is an effective and selective inhibitor of receptor-interacting protein 2 (RIP2). GSK2983559 free acid shows excellent activity in blocking many proinflammatory cytokine responses in human inflammatory bowel disease explant samples an

CU-115 is a selective and potent TLR8 antagonist with IC50 of 1.04 µM and =>50 µM for TLR8 and TLR7, respectively. CU-115 decreases production of TNF-α and IL-1β activated by R-848 in THP-1 cells.

IL-4 inhibitor is an inhibitor of IL-4.1It binds to IL-4 with a Kdvalue of 1.8 μM and inhibits IL-4 activity in a cell-based reporter assay (EC50= 1.81 μM). It is selective for IL-4 over IL-13 (EC50= 18.2 μM). IL-4 inhibitor inhibits IL-4-induced STAT6 phosphorylation in THP-1 monocytes (EC50= 3.1 μM), indicating inhibition of the IL-4-JAK1-STAT6 signaling pathway.

NLRP3-IN-NBC6 is a potent, selective NLRP3 inflammasome inhibitor with IC50 of 574 nM. NLRP3-IN-NBC6 acts independently of Ca 2+. NLRP3-IN-NBC6 inhibits Nigericin -induced inflammasome activation in THP-1 cells and Imiquimod -induced IL-1β release from LPS-primed bone marrow-derived macrophages (BMDMs) [1].

MLN-3897 (CCR1 antagonist 10) is an orally active antagonist of CCR1 with a Ki of 2.3 nM for 125I-MIP-1α binding to THP-1 cell membranes. MLN-3897 inhibits Akt signaling and MM cell survival and proliferation.

Adezmapimod (SB 203580) is a p38 MAPK inhibitor (IC50=0.3-0.5 μM) that is selective and ATP-competitive. Adezmapimod possesses autophagy and mitochondrial autophagy activating activity. Adezmapimod displays more than 100-fold higher selectivity than PKB, LCK, and GSK-3β.

C29 is a novel inhibitor of TLR2 1 and TLR2 6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2 1 signaling in murine macrophages.

Volasertib (BI 6727) (BI-6727) is a potent inhibitor of PLK1 (IC50: 0.87 nM), inducing mitotic arrest and apoptosis. It also inhibits PLK2 PLK3 (IC50s: 5 56 nM).

Nrf2 activator; inhibits Nrf2/Keap1 interaction. Induces upregulation of Nrf2 pathway downstream gene expression including heme-oxygenase 1. Suppresses LPS-induced TNF-α expression in THP-1 cells.

Streptazolin is a fungal metabolite originally isolated from S. viridochromogenes. It increases NF-κB activity when used at concentrations ranging from 60 to 130 μg/ml, at least in part, via PI3K signaling. Streptazolin enhances TNF-α secretion induced by LPS and enhances IL-8 secretion when used alone or in combination with LPS in THP-1 Blue cells.

C18 globotriaosylceramide is an endogenous sphingolipid found in mammalian cell membranes that is synthesized from lactosylceramide . It inhibits aggregation of human neutrophils induced by phorbol 12-myristate 13-acetate (PMA; 10008014) when used at a concentration of 1 μM. C18 globotriaosylceramide acts as a receptor for Shiga toxin in B cell-derived Raji cells and THP-1 monocytes. It accumulates in the brain, heart, kidney, liver, lung, and spleen in a mouse model of Fabry disease, a lysosomal storage disorder characterized by a deficiency in the enzyme α-galactosidase A. C18 globotriaosylceramide also accumulates in endothelial cells, pericytes, vascular smooth muscle cells, renal epithelial cells, dorsal ganglia neuronal cells, and myocardial cells in patients with Fabry disease.

C16 globotriaosylceramide is an endogenous sphingolipid found in mammalian cell membranes that is synthesized from C16 lactosylceramide . C16 globotriaosylceramide acts as a receptor for Shiga toxin in B cell-derived Raji cells and THP-1 monocytes. It accumulates in endothelial cells, pericytes, vascular smooth muscle cells, renal epithelial cells, dorsal ganglia neuronal cells, and myocardial cells in patients with Fabry disease. C16 globotriaosylceramide is also upregulated in plasma of patients with ovarian carcinoma compared to those with benign ovarian tumors or uterine fibroids.

Viscidulin II can be potential therapeutic agents against P. acnes-induced skin inflammation, it can significantly suppress P. acnes-induced IL-8 and IL-1β production in THP-1 cells, concomitant intradermal injection of viscidulin II with P. acnes can effectively attenuate P. acnes-induced ear swelling, and decrease the production of IL-6 and tumor necrosis factor-α in ear homogenates.

Sibiricine (Compound 8), an isoquinoline alkaloid extracted from the medicinal plant Corydalis crispa, exhibits substantial anti-inflammatory effects by inhibiting TNF-α production in LPS-activated THP-1 cells [1].

Evoxine is a selective inhibitor of CO2-induced immune suppression. It inhibits hypercapnic suppression of interleukin-6 and the chemokine CCL2 expression in human THP-1 macrophages.

Lucideric acid A (Lucidenic acid A) is a modulator of JNK and p38 and enhances LPS-induced immune responses in monocytic THP-1 cells possibly via the modulation of p38 and JNK/MAPKs activation.

Aspergillin PZ is a fungal metabolite originally isolated from A. awamori. It induces morphological deformation of P. oryzae conidia when used at a concentration of 89 nM. Aspergillin PZ is active against S. epidermidis (MIC = 20 μM) but not S. aureus, E. coli, or B. cereus (MICs = >20 μM). It is cytotoxic to HL-60 promyelocytic leukemia cells (IC50 = 56.61 μM) but not THP-1 acute monocytic leukemia or PC3 prostate cancer cells (IC50s = >80 μM).

Propargyl-PEG1-THP is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

STING agonist 12L is a stimulator of interferon genes (STING) agonist that exhibits binding affinity for both wild-type STING and its variants R232, AQ, and Q with half-maximal inhibitory concentrations (IC50s) of 1.15 µM for wild-type, 1.06 µM for R232, 0.61 µM for AQ, and 1.12 µM for Q. It effectively induces reporter gene expression in THP-1 and RAW 264.7 cells, with half-maximal effective concentrations (EC50s) of 0.38 µM and 12.94 µM, respectively. At a concentration of 5 µM, STING agonist 12L escalates the expression of IFNB1, CXCL10, and IL6 mRNA in THP-1 cells. When administered in vivo at a dose of 10 mg/kg, it enhances plasma IFN-β levels and considerably reduces tumor volume and the number of lung metastases in a B16/F10 murine melanoma model.

MS-PEG1-THP is a PEG-based linker for PROTACs which joins two essential ligands, crucial for forming PROTAC molecules. This linker enables selective protein degradation by leveraging the ubiquitin-proteasome system within cells.

FSL-1 TFA, a toll-like receptor 2/6 (TLR2/6) agonist derived from bacteria, bolsters resistance against experimental HSV-2 infection[1] and stimulates MMP-9 production via the TLR2 and NF-κB/AP-1 signaling pathways in monocytic THP-1 cells[2].

Diprovocim-1 is an agonist of the toll-like receptor 1/2 heterodimer.1It induces TNF-α release in THP-1 cells (EC50= 110 pM), an effect that can be inhibited by anti-TLR1 or anti-TLR2 antibodies. Diprovocim-1 (10 mg/kg) increases the production of ovalbumin-specific IgG1 in wild-type, but notTLR2-/-, mice sensitized to ovalbumin.2It also enhances anti-PD-L1 antibody-induced activation of cytotoxic T lymphocytes, reduction of tumor growth, and increases in survival in a B16/F10 murine melanoma model. 1.Morin, M.D., Wang, Y., Jones, B.T., et al.Diprovocims: A new and exceptionally potent class of toll-like receptor agonistsJ. Am. Chem. Soc.140(43)14440-14454(2018) 2.Wang, Y., Su, L., Morin, M.D., et al.Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in miceProc. Natl. Acad. Sci. U.S.A.115(37)E8698-E8706(2018)

Sirtuins (SIRTs) represent a distinct class of trichostatin A-insensitive lysyl-deacetylases (class III HDACs). Human SIRT1 is the homolog of yeast silent information regulator 2 (Sir2) and has been shown to regulate the activity of the p53 tumor suppressor and inhibit apoptosis. Small molecule activators of SIRT1, such as resveratrol, extend lifespan in yeast and C. elegans in a manner that resembles caloric restriction. CAY10591 has been identified as an activator of the enzyme SIRT1. This compound increases fluorescence by 233% in a SIRT1 activity assay. [Activator activity was defined as the percentage of signal increase relative to signal window in the following formula: 100 x (Sample - Signallow)/(Signalhigh - Signallow)]. CAY10591 suppresses TNF-α in a dose-dependent manner. In THP-1 cells, TNF-α levels decreased from 325 pg/ml (control) to 104 and 53 pg/ml with 20 and 60 µM CAY10591, respectively. This activator also has a significant dose-dependent effect on fat mobilization in differentiated adipocytes, which would indicate the potential of SIRT1 activators for anti-obesity or anti-diabetic purposes.

O-Allylvanillin, an O-allylchalcone derivative, exhibits anti-cancer properties by inhibiting the growth of THP-1, HL60, Hep-G2, and MCF-7 cells with IC50 values of 74.76 μM, 63.52 μM, 90.99 μM, and 90.11 μM, respectively [1].

Gastric inhibitory peptide (GIP) (22-51), a pro-atherogenic peptide comprised of 30 amino acids from the residues 22-51 of its precursor protein proGIP, is present in human plasma. It activates the degradation of IκB-α and the nuclear translocation of NF-κB in both macrophage-differentiated THP-1 cells and human aortic endothelial cells at a concentration of 1 µM. Additionally, in ApoE-/- mice, GIP (22-51) escalates the area of atherosclerotic lesions and plaque development in vivo.

STING agonist 1a is an agonist of stimulator of interferon genes (STING).1It induces expression of an IRF-inducible SEAP reporter gene in a cell-based assay (EC50= 16.77 μM). STING agonist 1a (12.5-100 μM) induces expression of IFN-β, IL-6, and chemokine (C-X-C motif) ligand 10 (CXCL10) in THP-1 cells, an effect that can be reversed by STING knockout or the STING inhibitor H-151 . 1.Hou, H., Yang, R., Liu, X., et al.Discovery of triazoloquinoxaline as novel STING agonists via structure-based virtual screeningBioorg. Chem.100103958(2020)

LSD1-IN-14, a powerful and specific inhibitor of LSD1 (with an IC50 value of 0.89 μM), effectively suppresses the growth of A549 and THP-1 cells and promotes the apoptosis of tumor cells [1].

CU-32 is an inhibitor of cyclic GMP-AMP (cGAMP) synthase (cGAS; IC50= 0.45 μM).1It reduces DNA-, but not Sendai virus-, induced dimerization of IFN regulatory factor 3 in THP-1 cells, indicating selectivity for the cGAS DNA sensing pathway over the RIG-I-MAVS RNA sensing pathway. It is also selective for cGAS over toll-like receptors (TLRs) at 50 μM. CU-32 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells when used at concentrations of 10, 30, and 100 μM. 1.Padilla-Salinas, R., Sun, L., Anderson, R., et al.Discovery of small-molecule cyclic GMP-AMP synthase inhibitorsJ. Org. Chem.85(3)1579-1600(2020)

R1487 Hydrochloride (R1487 (Hydrochloride)) is an orally bioavailable and highly selective inhibitors of p38α.

Euphohelioscopin A, an activator of protein kinase C (PKC), it inhibits proliferation and induces differentiation of the myeloid leukemia cell lines THP-1 and HL-60. Euphohelioscopin A has anti-inflammary activity, it exhibits moderate inhibitory activity

ORY-1001 is a KDM1A inhibitor (IC50 <20nM) with high selectivity against related FAD dependent aminoxidases (MAO-A/B, IL4I1, KDM1B >100uM, SMOX 7uM). Treatment of THP-1 (MLL-AF9) cells with ORY-1001, results in a time/dose dependent me2H3K4 accumulation a

Pactimibe is a ACAT inhibitor. It has anti-atherosclerotic activity.

STING agonist 12b is an agonist of stimulator of interferon genes (STING).1It binds to STING (Kd= 26.4 μM) and induces interferon reporter gene expression in cells expressing human or mouse STING (EC50s = 7.45 and 10.23 μM, respectively). STING agonist 12b (40 μM) induces expression of TNF-a, IL-6, IP-10, and IL-1b in THP-1 cells. 1.Hou, S., Lan, X.-j., Li, W., et al.Design, synthesis and biological evaluation of acridone analogues as novel STING receptor agonistsBioorg. Chem.95103556(2020)

THP-SS-PEG1-Tos is a 1 unit PEG ADC linker that is cleavable. It is employed during the synthesis of antibody-drug conjugates (ADCs)[1].

Tos-PEG4-THP is a polyethylene glycol (PEG) derivative utilized as a linker in the synthesis of PROTAC K-Ras Degrader-1, a potential therapeutic compound for targeted degradation of K-Ras protein [1].

LSD1-IN-18 is a potent, non-covalent, selective inhibitor of LSD1 (Ki:0.156 μM; KD: 0.075 μM).LSD1-IN-18 exhibited anti-proliferative effects in THP-1 leukemia cells and MDA-MB-231 breast cancer cells with IC50 (72 h) of 0.16 and 0.21 μM, respectively.

BDW568, a prodrug of BDW-OH, serves as a stimulator of interferon genes (STING) agonist. This compound effectively induces STING transcriptional activity, evidenced by a reporter assay in THP-1 cells, with an EC50 value of 7.6 µM. Furthermore, at a concentration of 50 µM, BDW568 prompts phosphorylation of TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3) within THP-1 cells, showcasing its biochemical activity in cellular signaling pathways.

Glutaminyl cyclases-IN-1 (IsoQC-IN-1) is a potent inhibitor of Glutaminyl cyclases (QC), which acts on human QC (IC50: 12 nM) and isoQC (IC 50:73 nM). Glutaminyl cyclases-IN-1 inhibited isoQC and selectively blocked CD47/SIRPα interaction. Glutaminyl cyclases-IN-1 also enhanced phagocytosis of THP-1 and U937 macrophages.

LSD1-IN-19 (compound 29) is a selective, potent, non-covalent inhibitor of LSD1 (Ki: 0.108 μM, KD: 0.068 μM). The 72h IC50 values were 0.17 and 0.40 μM, respectively.

Levonadifloxacin ((S)-(-)-Nadifloxacin; WCK 771), a broad-spectrum anti-staphylococcal agent, exhibits antibacterial activity against both Methicillin-susceptible Staphylococcus aureus (MSSA) and Methicillin-resistant S. aureus (MRSA) strains. It effectively reduces the presence of these bacteria when phagocytosed by THP-1 monocytes [1].

STING18 is a competitive ligand of stimulator of interferon genes (STING; IC50 = 0.068 μM in a radioligand binding assay).1 It inhibits cGAMP-induced IFN-β production (IC50 = 11 μM) but does not stimulate IFN-β production (EC50 = >30 μM) in THP-1 cells. |1. Siu, T., Altman, M.D., Baltus, G.A., et al. Discovery of a novel cGAMP competitive ligand of the inactive form of STING. Med. Chem. Lett. 10(1), 92-97 (2019).

THP-PEG4-Pyrrolidine(N-Me)-CH2OH, a PEG-based PROTAC linker, facilitates the synthesis of PROTAC K-Ras Degrader-1[1].

Piribedil (Trivastan) is a dopamine D2 agonist, used in the treatment of Parkinson's disease.

Andrograpanin (19-HYDROXY-8(17),13-LABDADIEN-16,15-OLIDE) is a bioactive compound from Andrographis paniculata. Andrograpanin has anti-inflammatory and anti-infectious properties.

IRAK4-IN-18 is a potent inhibitor of interleukin 1 receptor-associated kinase 4 (IRAK4) (IC50: 15 nM). IRAK4-IN-18 inhibits LPS-induced IL23 production in THP and DC cells and blocks the development of arthritis in rats, a model of arthritis. IRAK4-IN-18 can be used to study arthritic diseases.

STING modulator-5 (compound 38), a STING modulator, exhibits a pIC50 value of 9.5 and antagonizes peripheral blood mononuclear cells (PBMC) with a pIC50 value of 8.1. Additionally, it acts as an antagonist of THP-1 cells, making it applicable in immunological disease research [1].

MSA-2 dimer, a selective and orally active non-nucleotide STING agonist with a dissociation constant (Kd) of 145 μM, demonstrates prolonged antitumor and immunogenic activity. It non-covalently binds to STING as a dimer, showing greater permeability compared to cyclic dinucleotide[1].

Cathepsin C-IN-4 is a potent inhibitor (IC50: 65.6 nM) of histone C. Cathepsin C-IN-4 inhibits THP-1 cells (IC50: 203.4 nM) and U937 cells (IC50: 177.6 nM).