TPCA-1AbMoleM2300是一种选择性IκB激酶βIKKβ抑制剂通过阻断NF-κB信号通路发挥抗炎和调控细胞功能的作用。在细胞实验中TPCA-1以10 μM的浓度显著抑制TNF-α诱导的猪软骨细胞基质金属蛋白酶-13MMP-13的表达并阻断p65核转位该浓度下还可有效提升软骨细胞在炎症应激下的存活率[1]。TPCA-1在HeLa细胞中显著抑制IL-1β诱导的CCL-2释放并抑制NF-κB活化及p65核转位[2]。在脐带血来源的CD34⁺造血干细胞/祖细胞HSPCs培养体系中100 nM 的TPCA-1CAS No.507475-17-4处理10天可显著促进总细胞、CD34⁺CD38⁻及多能干性表型CD34⁺CD38⁻CD45RA⁻CD90⁺CD49f⁺细胞的增殖并增强其二次集落形成能力同时下调线粒体生物合成相关基因如Pgc1α、ClpP、Hsp10、Hsp60降低线粒体质量与膜电位减少线粒体ROS水平促进糖酵解代谢[3]。此外TPCA-1在小鼠腹腔巨噬细胞中能显著降低LipopolysaccharidesLPS脂多糖诱导的TNF-α表达[4]在成纤维细胞中TPCA-1预处理可抑制视黄醇Vitamin A诱导的单核细胞趋化蛋白-1MCP-1分泌提示视黄醇的作用依赖于NF-κB通路。在动物模型方面TPCA-1AbMoleM2300被广泛用于小鼠疾病模型研究在创伤后骨关节炎小鼠PTOA模型中通过循环机械负荷法诱导小鼠的关节损伤随后在其关节内给予100 μM TPCA-1溶液或负载TPCA-1的靶向纳米囊泡nanosomes结果显示能显著降低MMP13、IL1β、HIF-2α等炎症与分解代谢相关基因表达减少血清NO和LDH水平并通过IVIS成像一种活体成像技术与组织学评估证实了TPCA-1对软骨结构与功能的保护作用[5]在胶原Collagenase诱导的关节炎AIA小鼠模型中将TPCA-1负载于透明质酸修饰的金纳米笼HA-AuNCs/T/P后有效剂量可从20 mg/kg大幅降至0.016 mg/kg显著抑制关节肿胀及软骨骨破坏并有效降低TNF-α和IL-6水平[6]在急性肺损伤和腹膜炎小鼠模型中TPCA-1被包载于表面修饰抗ICAM-1抗体的pH响应型纳米颗粒TPCA-1NPs-anti-ICAM-1经静脉注射后可靶向炎症部位在酸性微环境中释放药物显著减少炎症细胞浸润[7]在慢性牙周炎小鼠模型中采用结扎法诱导疾病静脉注射TPCA-1可抑制牙龈组织中促炎因子表达及NF-κB信号活化[8]。综上TPCA-1AbMoleM2300在多种细胞系如猪软骨细胞、HeLa细胞、HSPCs、小鼠巨噬细胞、成纤维细胞及小鼠疾病模型中展现出稳定的NF-κB通路抑制活性。范例详解AAPS PharmSciTech. 2020 Nov 2;21(8):298.实验人员构建了一种金纳米笼AuNCs用于负载AbMole的TPCA-1AbMoleM2300TPCA-1是一种选择性IKK-2抑制剂通过抑制NF-κB通路发挥抗炎作用。结果显示TPCA-1与金纳米笼的固有抗炎特性通过减少TLR4和NF-κB表达形成协同效应并在关节炎AIA小鼠模型中改善了爪部肿大和骨损伤。Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis[9]参考文献及鸣谢[1] Bhatti, F. U. R.; Hasty, K. A.; Cho, H. Anti-inflammatory role of TPCA-1 encapsulated nanosomes in porcine chondrocytes against TNF-alpha stimulation. Inflammopharmacology2019, 27 (5), 1011-1019.[2] Tao, L.; Liu, S.; Xiong, J.; et al. IL-1beta promotes cervical cancer through activating NF-kappaB/CCL-2. International journal of clinical and experimental pathology2021, 14 (4), 426-433.[3] Sun, Q.; Fu, Y.; Zhu, X.; et al. Continuous NF-kappaB pathway inhibition promotes expansion of human phenotypical hematopoietic stem/progenitor cells through metabolism regulation. Experimental cell research2021, 399 (2), 112468.[4] Kiaei, N.; Malik, A.; Idahosa, S. O.; et al. Python-derived 16alpha-Hydroxylated Bile Acid, Pythocholic Acid is a ligand for TGR5, not farnesoid X receptors and vitamin D receptors. Biochemical and biophysical research communications2025, 751, 151453.[5] Jung, B.; Bhatti, F. U.; Mummareddy, H.; et al. Targeted nanosome delivery of TPCA-1 for modulating inflammation in a mouse model of post-traumatic osteoarthritis. Nanomedicine : nanotechnology, biology, and medicine2025, 67, 102827.[6] Zhao, J. Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation. Pharmaceutics2019, 11 (3).[7] Zhao, L.; Liu, J.; Li, X.; et al. De Novo Development of Bioresponsive Nanoparticles With Antimicrobial Activity to Treat Bacterial Infections. Advanced healthcare materials2026, e05683.[8] Wang, B.; Bai, S.; Wang, J.; et al. TPCA-1 negatively regulates inflammation mediated by NF-kappaB pathway in mouse chronic periodontitis model. Molecular oral microbiology2021, 36 (3), 192-201.[9] Wang, Z.; Yang, J.; Yang, Y.; et al. Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis. AAPS PharmSciTech2020, 21 (8), 298.
AbMole丨TPCA-1：IKKβ抑制剂在炎症损伤及干细胞等研究中的应用
发布时间：2026/8/1 4:03:26
TPCA-1AbMoleM2300是一种选择性IκB激酶βIKKβ抑制剂通过阻断NF-κB信号通路发挥抗炎和调控细胞功能的作用。在细胞实验中TPCA-1以10 μM的浓度显著抑制TNF-α诱导的猪软骨细胞基质金属蛋白酶-13MMP-13的表达并阻断p65核转位该浓度下还可有效提升软骨细胞在炎症应激下的存活率[1]。TPCA-1在HeLa细胞中显著抑制IL-1β诱导的CCL-2释放并抑制NF-κB活化及p65核转位[2]。在脐带血来源的CD34⁺造血干细胞/祖细胞HSPCs培养体系中100 nM 的TPCA-1CAS No.507475-17-4处理10天可显著促进总细胞、CD34⁺CD38⁻及多能干性表型CD34⁺CD38⁻CD45RA⁻CD90⁺CD49f⁺细胞的增殖并增强其二次集落形成能力同时下调线粒体生物合成相关基因如Pgc1α、ClpP、Hsp10、Hsp60降低线粒体质量与膜电位减少线粒体ROS水平促进糖酵解代谢[3]。此外TPCA-1在小鼠腹腔巨噬细胞中能显著降低LipopolysaccharidesLPS脂多糖诱导的TNF-α表达[4]在成纤维细胞中TPCA-1预处理可抑制视黄醇Vitamin A诱导的单核细胞趋化蛋白-1MCP-1分泌提示视黄醇的作用依赖于NF-κB通路。在动物模型方面TPCA-1AbMoleM2300被广泛用于小鼠疾病模型研究在创伤后骨关节炎小鼠PTOA模型中通过循环机械负荷法诱导小鼠的关节损伤随后在其关节内给予100 μM TPCA-1溶液或负载TPCA-1的靶向纳米囊泡nanosomes结果显示能显著降低MMP13、IL1β、HIF-2α等炎症与分解代谢相关基因表达减少血清NO和LDH水平并通过IVIS成像一种活体成像技术与组织学评估证实了TPCA-1对软骨结构与功能的保护作用[5]在胶原Collagenase诱导的关节炎AIA小鼠模型中将TPCA-1负载于透明质酸修饰的金纳米笼HA-AuNCs/T/P后有效剂量可从20 mg/kg大幅降至0.016 mg/kg显著抑制关节肿胀及软骨骨破坏并有效降低TNF-α和IL-6水平[6]在急性肺损伤和腹膜炎小鼠模型中TPCA-1被包载于表面修饰抗ICAM-1抗体的pH响应型纳米颗粒TPCA-1NPs-anti-ICAM-1经静脉注射后可靶向炎症部位在酸性微环境中释放药物显著减少炎症细胞浸润[7]在慢性牙周炎小鼠模型中采用结扎法诱导疾病静脉注射TPCA-1可抑制牙龈组织中促炎因子表达及NF-κB信号活化[8]。综上TPCA-1AbMoleM2300在多种细胞系如猪软骨细胞、HeLa细胞、HSPCs、小鼠巨噬细胞、成纤维细胞及小鼠疾病模型中展现出稳定的NF-κB通路抑制活性。范例详解AAPS PharmSciTech. 2020 Nov 2;21(8):298.实验人员构建了一种金纳米笼AuNCs用于负载AbMole的TPCA-1AbMoleM2300TPCA-1是一种选择性IKK-2抑制剂通过抑制NF-κB通路发挥抗炎作用。结果显示TPCA-1与金纳米笼的固有抗炎特性通过减少TLR4和NF-κB表达形成协同效应并在关节炎AIA小鼠模型中改善了爪部肿大和骨损伤。Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis[9]参考文献及鸣谢[1] Bhatti, F. U. R.; Hasty, K. A.; Cho, H. Anti-inflammatory role of TPCA-1 encapsulated nanosomes in porcine chondrocytes against TNF-alpha stimulation. Inflammopharmacology2019, 27 (5), 1011-1019.[2] Tao, L.; Liu, S.; Xiong, J.; et al. IL-1beta promotes cervical cancer through activating NF-kappaB/CCL-2. International journal of clinical and experimental pathology2021, 14 (4), 426-433.[3] Sun, Q.; Fu, Y.; Zhu, X.; et al. Continuous NF-kappaB pathway inhibition promotes expansion of human phenotypical hematopoietic stem/progenitor cells through metabolism regulation. Experimental cell research2021, 399 (2), 112468.[4] Kiaei, N.; Malik, A.; Idahosa, S. O.; et al. Python-derived 16alpha-Hydroxylated Bile Acid, Pythocholic Acid is a ligand for TGR5, not farnesoid X receptors and vitamin D receptors. Biochemical and biophysical research communications2025, 751, 151453.[5] Jung, B.; Bhatti, F. U.; Mummareddy, H.; et al. Targeted nanosome delivery of TPCA-1 for modulating inflammation in a mouse model of post-traumatic osteoarthritis. Nanomedicine : nanotechnology, biology, and medicine2025, 67, 102827.[6] Zhao, J. Hyaluronic Acid-Modified and TPCA-1-Loaded Gold Nanocages Alleviate Inflammation. Pharmaceutics2019, 11 (3).[7] Zhao, L.; Liu, J.; Li, X.; et al. De Novo Development of Bioresponsive Nanoparticles With Antimicrobial Activity to Treat Bacterial Infections. Advanced healthcare materials2026, e05683.[8] Wang, B.; Bai, S.; Wang, J.; et al. TPCA-1 negatively regulates inflammation mediated by NF-kappaB pathway in mouse chronic periodontitis model. Molecular oral microbiology2021, 36 (3), 192-201.[9] Wang, Z.; Yang, J.; Yang, Y.; et al. Targeted and Combined TPCA-1-Gold Nanocage Therapy for In Vivo Treatment of Inflammatory Arthritis. AAPS PharmSciTech2020, 21 (8), 298.
