HSF1A
目录号 : GC32437
HSF1A是热休克转录因子1(HSF1)的激活剂。
Cas No.:1196723-93-9
Sample solution is provided at 25 µL, 10mM.
HSF1A is an activator of Heat Shock Transcription Factor 1 (HSF1) [1]. HSF1A inhibits the activity of the molecular chaperone TRiC/CCT, thereby activating HSF1 and enhancing cellular resistance to protein misfolding and stress [2-3]. HSF1A is primarily used to treat neurodegenerative diseases [4].
In CD150+CD48-LSK hematopoietic stem cells (HSCs), HSF1A (8μM; 10d) enhances the serial reconstitutive activity of HSCs cultured in vitro [5]. In chinese hamster ovary cells, HSF1A (200µM; 1h) protects cells from pertussis toxin-induced cytotoxicity [6].
In wistar kyoto rats, HSF1A (100mg/kg; ip; 4 weeks) ameliorates doxorubicin-induced heart failure in vivo [7]. In ovalbumininduced allergic asthma mice model, HSF1A (1.3g/kg; ig; 5 weeks) treatment not only reduces inflammation and oxidative stress but also significantly attenuates airway fibrosis [8].
References:
[1]. Neef D W, Jaeger A M, Gomez-Pastor R, et al. A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1[J]. Cell reports, 2014, 9(3): 955-966.
[2]. Neef D W, Turski M L, Thiele D J. Modulation of heat shock transcription factor 1 as a therapeutic target for small molecule intervention in neurodegenerative disease[J]. PLoS biology, 2010, 8(1): e1000291.
[3]. Steinemann M, Schlosser A, Jank T, et al. The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B[J]. Proceedings of the National Academy of Sciences, 2018, 115(38): 9580-9585.
[4]. Liu A Y, Minetti C A, Remeta D P, et al. HSF1, aging, and neurodegeneration[J]. Cell Biology and Translational Medicine, Volume 18: Tissue Differentiation, Repair in Health and Disease, 2022: 23-49.
[5]. Kruta M, Sunshine M J, Chua B A, et al. Hsf1 promotes hematopoietic stem cell fitness and proteostasis in response to ex vivo culture stress and aging[J]. Cell stem cell, 2021, 28(11): 1950-1965. e6.
[6]. Jia J, Zoeschg M, Barth H, et al. The chaperonin TRiC/CCT inhibitor HSF1A protects cells from intoxication with pertussis toxin[J]. Toxins, 2024, 16(1): 36.
[7]. Huang C Y, Kuo W W, Lo J F, et al. Doxorubicin attenuates CHIP-guarded HSF1 nuclear translocation and protein stability to trigger IGF-IIR-dependent cardiomyocyte death[J]. Cell death & disease, 2016, 7(11): e2455-e2455.
[8]. Liu X, Zhang Y, Wu H, et al. HSF1 in macrophages suppressed the progression of asthma via modulating SIRPα/SHP2—Dectin-1/SYK mediated ROS and inflammatory responses[J]. Scientific Reports, 2025, 15(1): 29741.
HSF1A是热休克转录因子1(HSF1)的激活剂 [1]。HSF1A抑制分子伴侣TRiC/CCT的活性,从而激活HSF1,增强细胞对蛋白质错误折叠和应激的抵抗力 [2-3]。HSF1A主要用于治疗神经退行性疾病 [4]。
在CD150+CD48-LSK造血干细胞(HSC)中,HSF1A(8μM;10d)可增强体外培养的HSC的连续重建活性 [5]。在中国仓鼠卵巢细胞中,HSF1A(200μM;1h)可保护细胞免受百日咳毒素诱导的细胞毒性 [6]。
在wistar kyoto大鼠中,HSF1A(100 mg/kg;ip;4周)可改善体内阿霉素诱导的心力衰竭 [7]。在卵清蛋白诱导的过敏性哮喘小鼠模型中,HSF1A(1.3g/kg;ig;5周)治疗不仅可以减轻炎症和氧化应激,而且还可以显著减轻气道纤维化 [8]。
Cell experiment [1]: | |
Cell lines | CD150+CD48-LSK hematopoietic stem cells (HSCs) |
Preparation Method | CD150+CD48-LSK HSCs were sorted from the bone marrow of young adult mice directly into 96-well v-bottom plates at a density of 10 cells/well containing freshly made basic HSC culture medium (Prime-XV Mouse Hematopoietic Cell Medium) with SCF (50ng/ml), TPO (50ng/ml), 2-Mercaptoethanol (50μM) and bovine serum albumin (BSA; 0.1%). When specified, basic HSC medium was supplemented with 17-AAG (5nM) or HSF1A (8μM) in 0.02% DMSO. As a control, basic HSC medium was supplemented with 0.02% DMSO. |
Reaction Conditions | 8μM; 10d |
Applications | HSF1A enhances the serial reconstitutive activity of HSCs cultured in vitro. |
Animal experiment [2]: | |
Animal models | Wistar Kyoto rats |
Preparation Method | Ten-week-old Wistar Kyoto (WKY) rats were used. Rats were housed at a constant temperature (22℃) with a 12-hour light/dark cycle and provided with food and tap water. The animals were divided into three groups: WKY rats (control group), Doxorubicin (DOX) rats, and DOX rats treated with HSF1A. Each group contained five animals. The DOX group received intraperitoneal injections of DOX (5mg/kg) for 6 consecutive weeks, reaching a cumulative dose of 30mg/kg, which has been shown to be cardiotoxic. HSF1A, a small molecule HSF1 activator, was also administered intraperitoneally (100mg/kg/day). |
Dosage form | 100mg/kg; ip; 4 weeks |
Applications | HSF1A ameliorates doxorubicin-induced heart failure in vivo. |
References: |
Cas No. | 1196723-93-9 | SDF | |
Canonical SMILES | O=S(C1=CC=C(CC)C=C1)(NC2=CC(C3=CC=CS3)=NN2C4=CC=CC=C4)=O | ||
分子式 | C21H19N3O2S2 | 分子量 | 409.52 |
溶解度 | DMSO : ≥ 150 mg/mL (366.28 mM);Water : < 0.1 mg/mL (insoluble) | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
1 mM | 2.4419 mL | 12.2094 mL | 24.4188 mL |
5 mM | 0.4884 mL | 2.4419 mL | 4.8838 mL |
10 mM | 0.2442 mL | 1.2209 mL | 2.4419 mL |
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