human pbmcs

ML604440 是一种特异性的、有效的、细胞可渗透的蛋白酶体 β1i (LMP2) 亚基抑制剂，能够破坏 MHC I 类细胞表面表达，IL-6 分泌以及 naïve T helper 向 17 T helper 细胞的分化。它可以改善实验性结肠炎和 EAE 疾病。

Lenacapavir （ GS-6207） 是美国食品药品监督管理局、欧洲药品管理局和加拿大卫生部批准用于治疗 MDR HIV-1 感染的首创 HIV-1 衣壳抑制剂。[3]

Gardiquimod 可抑制巨噬细胞和活化的外周血单个核细胞的HIV-1感染。 它是一种咪唑喹啉类似物，是一种 TLR7 8 激动剂。

HPK1-IN-56 (Compound A29) 是一种HPK1抑制剂，IC50为2.70 nM，抑制下游 p-SLP76 在Jurkat T细胞中的IC50为8.1 nM。此外，HPK1-IN-56 能诱导人PBMCs中IL-2的产生，并表现出抗癌作用，提升T细胞的杀伤能力及增强抗PD-1抗体的抗肿瘤功效。

CK176 is a capsid targeted inhibitor of HIV-1 replication. CK176 shows an 11-fold improvement over I-XW-053 in blocking HIV-1 replication in primary human peripheral blood mononuclear cells (PBMCs).

M199, a novel inhibitor of TLR3 9 activation, induces secretion of IL-6, IL-8 and TNFalpha in human PBMCs.

Tenofovir exalidex (CMX 157) 是一种非环核苷酸类似物 Tenofovir 的脂质结合物，对野生型和抗逆转录病毒耐药的 HIV 毒株，包括多药核苷 核苷酸类似物耐药病毒，都有活性。Tenofovir exalidex 对人外周血单个核细胞中所有主要的HIV-1和HIV-2亚型以及单核细胞来源的巨噬细胞中所有 HIV-1 菌株具有活性，EC50 范围在 0.2 和 7.2 nM 之间。Tenofovir exalidex 具有口服活性，无明显毒性。Tenofovir exalidex 对 HBV 也有活性。

SMU127 is an agonist of the toll-like receptor 1 2 (TLR1 2) heterodimer.1It induces NF-κB signaling in cells expressing human TLR2 (EC50= 0.55 μM) but not cells expressing human TLR3, -4, -5, -7, or -8 when used at concentrations ranging from 0.1 to 100 μM. SMU127 induces the production of TNF-α in isolated human peripheral blood mononuclear cells (PBMCs) when used at concentrations ranging from 0.01 to 1 μM.In vivo, SMU127 (0.1 mg animal) reduces tumor volume in a 4T1 murine mammary carcinoma model. 1.Chen, Z., Cen, X., Yang, J., et al.Structure-based discovery of a specific TLR1-TLR2 small molecule agonist from the ZINC drug library databaseChem. Commun. (Camb.)54(81)11411-11414(2018)

CC-90005 is a potent, selective and orally active inhibitor of protein kinase C-θ (PKC-θ), with an IC50 of 8 nM. CC-90005 shows selectivity for PKC-θ over PKC-δ (IC50=4440 nM). CC-90005 can inhibit T cell activation by IL-2 expression[1]. CC-90005 shows the exquisite selectivity of CC-90005, with IC50s for all other family members of >3 μM[1].CC-90005 is a moderate inhibitor of both CYP2C9 (IC50=8 μM) and CYP2C19 (IC50=5.9 μM) in human liver microsomes[1].CC-90005 inhibits IL-2 expression in LRS_WBC human PBMCs, with an IC50 of 0.15 μM[1].CC-90005 (1-10 μM; 24 h) inhibits T cell proliferation in PBMCs by 51% at 1 μM and 88% at 3 μM[1]. CC-90005 (3-30 mg kg; p.o. twice daily for 4 days) significantly reduces the popliteal lymph node (PLN) size in a model of chronic T cell activation[1].CC-90005 (100 mg kg; a single p.o.) significantly inhibits plasma and spleen IL-2 release by 51 and 54%, respectively[1].CC-90005 exhibits reasonable oral bioavailability (66 and 46%) and Cmax (1.18 and 1.2 μM) following oral administration (10 and 3 mg kg) in rat and dog, respectively[1].CC-90005 exhibits the mean residence time (0.52 and 2.0 h), CL (69.1 and 20.5 mL min kg) and Vss (2.11 and 2.44 L kg) following intravenous administration (2 and 1 mg kg) in rat and dog, respectively[1]. [1]. Papa P, et, al. Discovery of the Selective Protein Kinase C-θ Kinase Inhibitor, CC-90005. J Med Chem. 2021 Aug 26;64(16):11886-11903.

O-Demethyl apremilast is an active metabolite of the phosphodiesterase 4 (PDE4) inhibitor apremilast .1It inhibits the activity of PDE4 isolated from U937 cells and LPS-induced TNF-α production in isolated human peripheral blood mononuclear cells (PBMCs; IC50s = 8.3 and 5.6 μM, respectively). O-Demethyl apremilast is also an oxidative degradation product of apremilast.2,3 1.Hoffmann, M., Kumar, G., Schafer, P., et al.Disposition, metabolism and mass balance of [14C]apremilast following oral administrationXenobiotica41(12)1063-1075(2011) 2.Lu, Y., Shen, X., Hang, T., et al.Identification and characterization of process-related substances and degradation products in apremilast: Process optimization and degradation pathway elucidationJ. Pharm. Biomed. Anal.14170-78(2017) 3.Bhole, R.P., Naksakhare, S.R., and Bonde, C.G.A stability indicating HPTLC method for apremilast and identification of degradation products using MS MSJ. Pharm. Sci. & Res.11(5)1861-1869(2019)

Ganglioside GT1b is a trisialoganglioside that is characterized by having two sialic residues linked to the inner galactose unit. It binds to the neurotoxins botulinum toxin serotype A (BTxA), BTxA heavy chain, and tetanus toxin with IC50 values of 11, 0.74, and 7.2 μM, respectively.[1] Ganglioside GT1b-containing liposomes bind to the major coat protein VP1 from Merkel cell polyomavirus (MCPyV), which has been identified in Merkel cell carcinomas, identifying ganglioside GT1b as a putative MCPyV receptor. [2] Ganglioside GT1b decreases production of IL-6, IL-10, IgG, IgM, and IgA in human peripheral blood mononuclear cells (PBMCs) by 31.4, 30.5, 60, 59.5, and 58%, respectively, when used at a concentration of 10 μM [3] . Ganglioside GT1b mixture contains ganglioside GT1b molecular species with C18:1 and C20:1 sphingoid backbones.

ODN D-SL03是C类CpG寡核苷酸，能诱导PBMCs产生高水平IFN-α，激活人B细胞、NK细胞和单个核细胞，同时上调PBMCs亚群表面CD80、CD86和HLA-DR的表达，还能抑制肿瘤生长。ODN D-SL03序列：5'-tcgcgaacgttcgccgcgttcgaacgcgg-3'。

INX-SM-6适用于靶向输送抗炎药物。它能在PBMCS细胞中抑制LPS引发的IL-1β产生。

TLR8 agonist6 (Compound A)，具有EC50值为0.052 μM的TLR8激动特性，能够以EC50为0.031 μM的效力促进人PBMC中的IL-12p40生成。适用于抗病毒、抗感染、自身免疫和肿瘤相关研究领域。

Rademikibart (CBP-201) 是一款针对IL-4Rα的人源化单克隆抗体，其与人IL-4Rα的结合亲和力KD值为20.7 pM。该抗体不与其他物种的IL-4Rα发生交互作用。Rademikibart 能够抑制PBMC中IL-4及IL-13介导的STAT6信号通路、TF-1细胞的增殖以及TARC的产生，显示出其在中到重度Th2型炎症性疾病研究中的应用潜力。

Cathelicidin-2 (CATH-2) (128-153) 是一种合成抗菌肽，对应于鸡CATH-2的128至153个氨基酸。该化合物对E. coli、S. aureus、S. enteritidis和B. globigii展示出浓度依赖性的活性。CATH-2 (128-153) (40 µM) 可诱导孤立的鸡红细胞溶解，但对孤立的人外周血单个核细胞(PBMCs)无细胞毒性。它能促进化学因子(C-C-基序)配体2 (CCL2)的产生，并抑制LPS诱导的TNF-α、IL-6、IL-8和IL-10在孤立的人PBMCs中的产生。

HOXB7 (8-25) 是 homeobox B7 (HOXB7) 的肽段，是细胞增殖的主要调控因子和肿瘤基因途径的激活剂。通过 HOXB7 (8-25) 肽脉冲的树突状细胞展示抗原，这些树突状细胞来源于分离的人类外周血单核细胞（PBMCs），刺激CD4+辅助T细胞的激活和IFN-γ的产生，从而引发特异性和多向性肿瘤反应性的抗肿瘤反应。

EGFRvIII peptide是一种合成肽，对应于特异性肿瘤、具有持续激活性的EGFR变体EGFRvIII的融合接头，该变体缺少野生型EGFR的第6至273个氨基酸。在25 µg/ml的浓度下，它能与MHC I类亚型HLA-A*0201阳性的T2细胞结合。在用于分离的人外周血单个核细胞（PBMCs）衍生的树突状细胞中，EGFRvIII peptide可诱导抗原呈递，进而刺激CD8+细胞毒性T淋巴细胞的激活和IFN-γ产生。与toll样受体5（TLR5）激动剂鞭毛蛋白B共同免疫EGFRvIII peptide（15 µg/动物），在正交GL261胶质母细胞瘤小鼠异种移植模型中，增加了CD8+ T细胞数量，减少了调节性T细胞（Tregs）数量，减少了肿瘤体积，并提高了生存率。

M04 acts as a stimulator of interferon genes (STING) agonist, effectively inducing IFN reporter gene expression in HEK293T cells equipped with wild-type human STING. Its activity is specific, not affecting HEK293T cells with the R71H-G230A-R293Q (HAQ) human STING variant or mouse RAW 264.7 cells, showcasing allelic- and species-dependent effects at a concentration of 75 µM. This compound also stimulates the production of TNF-α, IL-10, IL-1β, and IL-12p70 in human peripheral blood mononuclear cells (PBMCs). At 50 µM, M04 enhances human monocyte-derived dendritic cells' expression of HLA-DR (MHC class II receptor) and co-stimulatory molecules CD40, CD80, and CD86, improving T cell cross-priming in an ex vivo assay.

d2T, a nucleoside analog of thymidine, exhibits antiviral activity by inhibiting HIV replication in infected human peripheral blood mononuclear cells (PBMCs; EC50 = 0.17 µM). Additionally, 3′-deoxy Thymidine at concentrations of 1, 3, 10, or 30 µM significantly decreases viral plaque formation in CV-1 cells infected with herpes simplex virus 1 (HSV-1).

PROTACHPK1 Degrader-2 (compound 3)，一种针对HPK1的PROTAC降解剂，在人PBMC中表现出23 nM的DC50。该化合物在癌症研究领域具有重要作用。

(+)-Norglaucine shows cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuc