thp-1 cells

Cisplatin-resistant cells-IN-1 (Compound 8) exhibits high cytotoxicity against Cisplatin-resistant cells and effectively diminishes metabolic activity at low nanomolar concentrations, with an IC50 ranging from 0.14 to 1.79 μM in various resistant cell lines, including A549 A549-R, K562 K562-R, and MCF-7 MCF-7TamR [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.

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.

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

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.

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

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.

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.

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)

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.

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].

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].

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)

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.

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).

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.

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.

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.

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].

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.

CAY10748 is an agonist of stimulator of interferon genes (STING; IC50= 0.3794 μM in a competition binding assay).1It activates STING in STING-expressing, but not STING knockout, THP-1 cells (EC50s = 0.287 and >100 μM, respectively, in a reporter assay). It induces phosphorylation of STING at the serine in position 366, as well as phosphorylation of TBK1 and IFN regulatory factor 3 (IRF3), indicating activation of the STING-TBK1-IRF3 signaling pathway. CAY10748 increases the secretion of IFN-β and the levels of chemokine (C-X-C motif) ligand 10 (CXCL10), and IL-6 in peripheral blood mononuclear cells (PBMCs) when used at a concentration of 10 μM. It also reduces tumor growth in a CT26 murine colon cancer model when administered at a dose of 0.15, but not 1.5, mg/kg. 1.Xi, Q., Wang, M., Jia, W., et al.Design, synthesis, and biological evaluation of amidobenzimidazole derivatives as stimulator of interferon genes (STING) receptor agonistsJ. Med. Chem.63(1)260-282(2019)

HGGPPS-IN-1 is an analogue of C-2-substituted thienopyrimidine-based bisphosphonates (C2-ThP-BPs). HGGPPS-IN-1 has an effective inhibitory effect on human geranyl geranyl pyrophosphate synthase (hGGPPS). HGGPPS-IN-1 can selectively induce apoptosis of multiple myeloma (MM) cells. HGGPPS-IN-1 showed anti-myeloma activity in vivo.

CCX140 (CCX140-B) (CCX140-B) is an antagonist of CCR2.

NOD2 antagonist 1 (compound 32) is an effective and selective NOD2 antagonist (IC50: 5.23 μM). In THP-1 cells, it represses Muramyl DiDP (MDP)-induced IL-8 secretion and, in PBMCs cells, inhibits MDP-induced elevation of IL-6, IL-10, and TNF-α.

IRAK4-IN-18 is a potent inhibitor of interleukin 1 receptor-associated kinase 4 (IRAK4) (IC50: 15 nM). It inhibits LPS-induced IL23 production in THP and DC cells and blocks the development of arthritis in rats, making it useful for studying 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).

Alpinone 3-acetate showed anti-inflammatory effects and inhibited the inflammatory response in mouse ear edema models induced by 12-O-tetradecanophenol 13-acetate. Alpinone 3-acetate is a derivative of Alpinone. Alpinone is an active natural compound derived from sunflower with immunomodulatory and antiviral activities.

Manumycin A is an antibiotic with anticancer activity and is a mammalian thioredoxin reductase-1 (TrxR-1) inhibitor.Manumycin A inhibits the production of IL-1β, IL-6, and IL-8 in TNF alpha-stimulated THP-1 cells and peripheral blood mononuclear cells in a dose-dependent manner, inducing apoptosis.

NLRP3-IN-9 (INF-4E) is an inhibitor of NLRP3 ATPase and caspase-1. NLRP3-IN-9 acts by irreversibly trapping thiol nucleophiles, which prevents both ATP- and nigericin-triggered pyroptosis of human THP-1 cells in a time- and concentration-dependent manner.

IRAK4-IN-19 is a potent inhibitor of interleukin 1 receptor-associated kinase 4 (IRAK4) with an IC50 of 4.3 nM. It inhibits LPS-induced IL23 production in THP and DC cells and suppresses arthritis development in arthritic model rats. IRAK4-IN-19 can be used to study arthritic diseases.

2-chloro Palmitic acid is a monochlorinated form of palmitic acid . It is produced in a myeloperoxidase (MPO) and time-dependent manner in neutrophils stimulated by phorbol 12-myristate 13-acetate . 2-chloro Palmitic acid (10 μM) induces neutrophil extracellular trap (NET) formation (NETosis) in human neutrophils, increasing DNA release from neutrophils, colocalization of MPO with extracellular DNA (ecDNA), and trapping of E. coli. It increases COX-2 protein levels in human coronary artery endothelial cells (HCAECs) when used at a concentration of 50 μM and increases production of P-selectin, von Willebrand factor, and angiopoietin-2 in HCAECs, as well as neutrophil and platelet adherence, when used at a concentration of 10 μM. 2-chloro Palmitic acid (10-50 μM) also induces apoptosis in THP-1 cells and primary human monocytes and increases caspase-3 activity in THP-1 cells.

Propargyl-PEG4-acid is a PEG-based PROTAC linker used in the synthesis of BTK-IAP PROTACs, including Ibrutinib-based PROTAC 2 and its analogue PROTAC 3. PROTAC 3 induces BTK degradation with a DC50 of 200 nM in THP-1 cells[1].

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).

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.

AP-1, a miniaturized proteolysis-targeting chimera (PROTAC) incorporating an anaplastic lymphoma kinase (ALK) ligand connected to (±)-thalidomide via an ultrashort linker, effectively degrades ALK fusion proteins such as NPM-ALK in Karpas-299 cells and EML4-ALK and ALKF1174L in SN-N-SH and NCI H3122 cells, respectively. Concentrations ranging from 10 to 300 nM are sufficient for its action, which is hindered by the proteasome inhibitor MG-132. Demonstrating selectivity, AP-1 exhibits cytotoxicity towards ALK-dependent Karpas-299 cells with an IC50 value of 0.1265 nM, while showing significantly less toxicity to non-ALK-dependent THP-1 cells (IC50 = 2,704 nM). Furthermore, it effectively reduces tumor volume in NCI H3122 mouse xenograft models at doses of 25, 50, and 100 mg/kg.

CU-76 is an inhibitor of cyclic GMP-AMP synthase (cGAS; IC50= 0.24 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. CU-76 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)

TMI-1 (WAY-171318), a novel orally active inhibitor of ADAM17 (TACE) and MMP, induces tumor apoptosis in a breast cancer.

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)

STING Modulator-4 is a competitive modulator of STING, exhibiting a K_i value of 0.0933 μM for the R232H STING variant. It demonstrates an EC_50 of over 10 μM for p-IRF3 activation in THP-1 cells.

STING modulator-3 is a STING inhibitor with a Ki value of 43.1 nM in scintillation proximity assays, specifically targeting R232 STING. It does not affect IRF-3 activation or TNF-β induction in THP-1 cells.

Compound 13h (hGGPPS-IN-3) is a potent inhibitor of human geranylgeranyl pyrophosphate synthase (hGGPPS), characterized as a C-2-substituted thienopyrimidine-based bisphosphonate analogue (C2-ThP-BPs). It selectively induces apoptosis in multiple myeloma (MM) cells and demonstrates antimyeloma activity in vivo [1].

BAZ1A-IN-1 is a potent BAZ1A inhibitor with a KD value of 0.52 μM for the BAZ1A bromodomain, demonstrating strong anti-survival activity against cancer cell lines with high BAZ1A expression and weak or no activity against cancer cells with low BAZ1A expression.

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].

CAY10602 is a SIRT1 activator derived from high throughput screening for compounds that enhance SIRT1-mediated deacetylation of a SIRT1-specific substrate. Functional assays indicate that CAY10602 dose-dependently suppresses NF-κB-dependent induction of TNF-α by lipopolysaccharide in THP-1 cells, achieving approximately 75% inhibition at 60 μM without cytotoxicity.