TriptolideIL-2/MMP-3/MMP7/MMP19 inhibitor CAS# 38748-32-2 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
Cas No. | 38748-32-2 | SDF | Download SDF |
PubChem ID | 107985 | Appearance | White powder |
Formula | C20H24O6 | M.Wt | 360.40 |
Type of Compound | Diterpenoids | Storage | Desiccate at -20°C |
Synonyms | PG490 | ||
Solubility | DMSO : ≥ 33 mg/mL (91.56 mM) *"≥" means soluble, but saturation unknown. | ||
SMILES | CC(C)C12C(O1)C3C4(O3)C5(CCC6=C(C5CC7C4(C2O)O7)COC6=O)C | ||
Standard InChIKey | DFBIRQPKNDILPW-CIVMWXNOSA-N | ||
Standard InChI | InChI=1S/C20H24O6/c1-8(2)18-13(25-18)14-20(26-14)17(3)5-4-9-10(7-23-15(9)21)11(17)6-12-19(20,24-12)16(18)22/h8,11-14,16,22H,4-7H2,1-3H3/t11-,12-,13-,14-,16+,17-,18-,19+,20+/m0/s1 | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Triptolide has immunosuppressive, anti-inflammatory, and anti-cancer activities, it induces apoptosis in tumor cells by blocking NF-KB activation and sensitizing tumor cells for TNF-a induced programmed cell death, it inhibits TGF-β1-induced cell proliferation and migration of rat airway smooth muscle cells, by suppressing Smad signaling and NF-κB ,respectively. Triptolide is an inhibitor of heat shock factor (HSF1), inhibits HSP90-CDC37 binding and induces acetylation of HSP90, and also inhibits MDM2 expression in a dose-dependent manner with IC50 values range from 47 to 73 nM. |
Targets | NF-kB | IkB | p65 | TGF-β/Smad | ERK | IKK | HSF-1 | HSP90 | MDM2 |
In vitro | Triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1.[Pubmed: 25511707]Biochem Biophys Res Commun. 2015 Jan 16;456(3):815-20.Epstein-Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities.
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In vivo | Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model.[Pubmed: 25448849]Mol Cell Endocrinol. 2015 Jan 5;399:346-53.The RANKL-induced NF-κB signaling pathway is required for osteoclast formation and function.
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Cell Research | Triptolide inhibits cell proliferation and tumorigenicity of human neuroblastoma cells.[Pubmed: 25354591]Triptolide inhibits TGF-β1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling.[Pubmed: 25447441]Exp Cell Res. 2015 Feb 15;331(2):362-8.We have reported that Triptolide can inhibit airway remodeling in a murine model of asthma via TGF-β1/Smad signaling. In the present study, we aimed to investigate the effect of Triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism.
Mol Med Rep. 2015 Feb;11(2):791-6.Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance.
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Animal Research | Triptolide inhibits TGF-β1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-κB but not ERK1/2.[Pubmed: 25267491]Immunology. 2014 Sep 29.Airway remodeling contributes to increased mortality in asthma. We have reported that Triptolide can inhibit airway remodeling in a mouse asthma model. In this study, we aimed to investigate the effect of Triptolide on airway smooth muscle cells (ASMCs) proliferation, migration and the possible mechanism.
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Triptolide Dilution Calculator
Triptolide Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.7747 mL | 13.8735 mL | 27.7469 mL | 55.4939 mL | 69.3674 mL |
5 mM | 0.5549 mL | 2.7747 mL | 5.5494 mL | 11.0988 mL | 13.8735 mL |
10 mM | 0.2775 mL | 1.3873 mL | 2.7747 mL | 5.5494 mL | 6.9367 mL |
50 mM | 0.0555 mL | 0.2775 mL | 0.5549 mL | 1.1099 mL | 1.3873 mL |
100 mM | 0.0277 mL | 0.1387 mL | 0.2775 mL | 0.5549 mL | 0.6937 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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Triptolide is the major bioactive constituent extracted from the Chinese herb Tripterygium wilfordii.
Triptolide inhibit the expression of IL-2 in activated T cells and NF-κB mediated transcription activation [1]. Triptolide also can inhibit colony formation and the proliferation of tumor cells at extremely low concentrations.
Triptolide treatment at the concentration of 15 nM inhibited the invasion and migration of ovarian cancer cells SKOV3 and A2780. Triptolide inhibited MMP7 and MMP19 expression with a dose-dependent manner from 0 to 15 nM in ovarian cancer cells. Triptolide also enhanced expression of the E-cadherin in ovarian cancer cell, then, affected the migration and cell invation.[2] Triptolide triggered a CDK7-mediated degradation of RNAPII, including its robust anticancer properties. Triptolide induced Rpb1 decrease with a dose-dependent manner at lowest 100 nM, resulting to a significant RNAPII reduction in SKOV3 cells.[3] Triptolide caused significant decrease of cell viability in a dose-dependent manner with IC50 value of 74.3 nM in RSF (rheumatoid synovial fibroblasts). Triptolide also has inhibition effect on cell proliferation in RSF with IC50= 20.4 nM. Treatment with triptolide (100 nM) for 24 h caused distinctive morphological changes in synovial cells.[4] Triptolide induces apoptotic death of peripheral T cells and T cell hybridomas by increase of DEVD-cleavable caspases activity at 10-100 ng/ml.[5]
Triptolide also inhibited cytokine-induced MMP-3 expression at 125-150nM in primary human synovial fibroblasts, SW1353 cells, and human OA chondro-cytes protecting artilage from aggrecanase- and MMP -driven breakdown.[6]
References:
[1]. Qiu D, Zhao G, Aoki Y, Shi L, Uyei A, Nazarian S, Ng JC, Kao PN: Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation. J Biol Chem 1999, 274(19):13443-13450.
[2]. Zhao H, Yang Z, Wang X, Zhang X, Wang M, Wang Y, Mei Q, Wang Z: Triptolide inhibits ovarian cancer cell invasion by repression of matrix metalloproteinase 7 and 19 and upregulation of E-cadherin. Exp Mol Med 2012, 44(11):633-641.
[3]. Manzo SG, Zhou ZL, Wang YQ, Marinello J, He JX, Li YC, Ding J, Capranico G, Miao ZH: Natural product triptolide mediates cancer cell death by triggering CDK7-dependent degradation of RNA polymerase II. Cancer Res 2012, 72(20):5363-5373.
[4]. Kusunoki N, Yamazaki R, Kitasato H, Beppu M, Aoki H, Kawai S: Triptolide, an active compound identified in a traditional Chinese herb, induces apoptosis of rheumatoid synovial fibroblasts. BMC Pharmacol 2004, 4:2.
[5]. Yang Y, Liu Z, Tolosa E, Yang J, Li L: Triptolide induces apoptotic death of T lymphocyte. Immunopharmacology 1998, 40(2):139-149.
[6]. Liacini A, Sylvester J, Zafarullah M: Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun 2005, 327(1):320-327.
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Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-B activation and titanium particle-induced osteolysis in a mouse model.[Pubmed:25448849]
Mol Cell Endocrinol. 2015 Jan 5;399:346-53.
The RANKL-induced NF-kappaB signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-kappaB activation using a luciferase reporter gene assay in RAW264.7 cells, we identified Triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that Triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-B activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that Triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that Triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles.
Triptolide inhibits TGF-beta1-induced cell proliferation in rat airway smooth muscle cells by suppressing Smad signaling.[Pubmed:25447441]
Exp Cell Res. 2015 Feb 15;331(2):362-8.
BACKGROUND: We have reported that Triptolide can inhibit airway remodeling in a murine model of asthma via TGF-beta1/Smad signaling. In the present study, we aimed to investigate the effect of Triptolide on airway smooth muscle cells (ASMCs) proliferation and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentration of Triptolide before stimulated by TGF-beta1. Cell proliferation was evaluated by MTT assay. Flow cytometry was used to study the influence of Triptolide on cell cycle and apoptosis. Signal proteins (Smad2, Smad3 and Smad7) were detected by western blotting analysis. RESULTS: Triptolide significantly inhibited TGF-beta1-induced ASMC proliferation (P<0.05). The cell cycle was blocked at G1/S-interphase by Triptolide dose dependently. No pro-apoptotic effects were detected under the concentration of Triptolide we used. Western blotting analysis showed TGF-beta1 induced Smad2 and Smad3 phosphorylation was inhibited by Triptolide pretreatment, and the level of Smad7 was increased by Triptolide pretreatment. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation via negative regulation of Smad signaling pathway.
Triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes by down-regulating expression of a viral protein LMP1.[Pubmed:25511707]
Biochem Biophys Res Commun. 2015 Jan 16;456(3):815-20.
Epstein-Barr virus (EBV) infects various types of cells and mainly establishes latent infection in B lymphocytes. The viral latent membrane protein 1 (LMP1) plays important roles in transformation and proliferation of B lymphocytes infected with EBV. Triptolide is a compound of Tripterygium extracts, showing anti-inflammatory, immunosuppressive, and anti-cancer activities. In this study, it is determined whether Triptolide inhibits proliferation of Epstein-Barr virus-positive B lymphocytes. The CCK-8 assays were performed to examine cell viabilities of EBV-positive B95-8 and P3HR-1 cells treated by Triptolide. The mRNA and protein levels of LMP1 were examined by real time-PCR and Western blotting, respectively. The activities of two LMP1 promoters (ED-L1 and TR-L1) were determined by Dual luciferase reportor assay. The results showed that Triptolide inhibited the cell viability of EBV-positive B lymphocytes, and the over-expression of LMP1 attenuated this inhibitory effect. Triptolide decreased the LMP1 expression and transcriptional levels in EBV-positive B cells. The activity of LMP1 promoter ED-L1 in type III latent infection was strongly suppressed by Triptolide treatment. In addition, Triptolide strongly reduced growth of B95-8 induced B lymphoma in BALB/c nude mice. These results suggest that Triptolide decreases proliferation of EBV-induced B lymphocytes possibly by a mechanism related to down-regulation of the LMP1 expression.
Triptolide (TPL) improves locomotor function recovery in rats and reduces inflammation after spinal cord injury.[Pubmed:25547329]
Neurol Sci. 2015 May;36(5):701-5.
In this study, we studied the effect of Triptolide (TPL) on locomotor function in rats with spinal cord injury. A total of 40 rats were studied after dividing them in two major groups, one was experimental group denoted as TPL group while other was control group denoted as PBS group. Each group was subdivided in four subgroups having five rats each (n = 5). TPL was given intraperitonially at the rate of 5 mg/kg/day in TPL group while PBS was given at the same time interval in the same manner in control group for comparison. A reduction in the cavity area of tissue sections was observed by bright field microscopy from 0.22 +/- 0.05 to 0.12 +/- 0.05 mm(2) in experimental group after 28 days of treatment while BBB score also improved from 1 to 5 after 14 days of treatment. SPSS software, one way ANOVA, was used for recording statistical analysis and values were expressed as mean +/- SEM where P value of <0.01 was considered significant. The expression of I-kBalpha and NF-kB p65 was also studied using western blotting and after recording optical density (OD) values of western blots. It was observed that treatment with TPL significantly reduced the expression of these factors after 28 days of treatment compared with controls.
Triptolide inhibits TGF-beta1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-kappaB but not ERK1/2.[Pubmed:25267491]
Immunology. 2014 Sep 29.
BACKGROUND: Airway remodeling contributes to increased mortality in asthma. We have reported that Triptolide can inhibit airway remodeling in a mouse asthma model. In this study, we aimed to investigate the effect of Triptolide on airway smooth muscle cells (ASMCs) proliferation, migration and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentrations of Triptolide before stimulated by TGF-beta1. Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of Triptolide on cell cycle. Migration was measured by Transwell analysis. Signal proteins (NF-kappaB p65 and ERK1/2) were detected by western blotting analysis. LDH releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of Triptolide. RESULTS: Triptolide significantly inhibited TGF-beta1 induced ASMC proliferation and migration (p<0.05). The cell cycle was blocked at G1/S-interphase by Triptolide dose dependently. Western blotting analysis showed TGF-beta1 induced NF-kappaB p65 phosphorylation was inhibited by Triptolide pretreatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of Triptolide we used. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation and migration through inactivation of NF-kappaB pathway. This article is protected by copyright. All rights reserved.
Triptolide inhibits cell proliferation and tumorigenicity of human neuroblastoma cells.[Pubmed:25354591]
Mol Med Rep. 2015 Feb;11(2):791-6.
Triptolide is a diterpene triepoxide, extracted from the Chinese herb Tripterygium wilfordii Hook F, which has been shown to have antitumor activity in a number of cancers. Neuroblastoma is an aggressive extracranial pediatric solid tumor, with significant chemotherapeutic resistance. In this study, Triptolide was hypothesized to be a potential therapeutic agent for neuroblastoma. The effects of Triptolide on neuroblastoma cell growth and tumor development were investigated. Cell growth and proliferation were evaluated using a cell counting kit8 assay and a 5-bromo-2-deoxyuridine staining assay. Cell cycle and apoptosis were detected by flow cytometry. Reverse transcriptionquantitative polymerase chain reaction was conducted to detect the expression levels of the apoptosisassociated proteins, caspase3 and caspase9. The tumorigenicity of neuroblastoma cells was assessed by a soft agar clonogenic assay and an in vivo tumorigenic assay. The results demonstrated that exposure of BE(2)C human neuroblastoma cells to Triptolide resulted in a reduction in cell growth and proliferation, and the induction of cell death and apoptosis, together with cell cycle arrest in the S phase. A soft agar assay indicated that Triptolide inhibited the colonyforming ability of BE(2)C neuroblastoma cells. The xenograft experiment showed that Triptolide significantly reduced tumor growth and development in vivo. The data suggested that this Chinese herb may be a potential novel chemotherapeutic agent for neuroblastoma.
XPB, a subunit of TFIIH, is a target of the natural product triptolide.[Pubmed:21278739]
Nat Chem Biol. 2011 Mar;7(3):182-8.
Triptolide (1) is a structurally unique diterpene triepoxide isolated from a traditional Chinese medicinal plant with anti-inflammatory, immunosuppressive, contraceptive and antitumor activities. Its molecular mechanism of action, however, has remained largely elusive to date. We report that Triptolide covalently binds to human XPB (also known as ERCC3), a subunit of the transcription factor TFIIH, and inhibits its DNA-dependent ATPase activity, which leads to the inhibition of RNA polymerase II-mediated transcription and likely nucleotide excision repair. The identification of XPB as the target of Triptolide accounts for the majority of the known biological activities of Triptolide. These findings also suggest that Triptolide can serve as a new molecular probe for studying transcription and, potentially, as a new type of anticancer agent through inhibition of the ATPase activity of XPB.
PG490 (triptolide) cooperates with tumor necrosis factor-alpha to induce apoptosis in tumor cells.[Pubmed:10224110]
J Biol Chem. 1999 May 7;274(19):13451-5.
Progress in the treatment of solid tumors has been slow and sporadic. The efficacy of conventional chemotherapy in solid tumors is limited because tumors frequently have mutations in the p53 gene. Also, chemotherapy only kills rapidly dividing cells. Members of the tumor necrosis factor (TNF) family, however, induce apoptosis regardless of the p53 phenotype. Unfortunately, the cytotoxicity of TNF-alpha is limited by its activation of NF-kappaB and activation of NF-kappaB is proinflammatory. We have identified a compound called PG490, that is composed of purified Triptolide, which induces apoptosis in tumor cells and sensitizes tumor cells to TNF-alpha-induced apoptosis. PG490 potently inhibited TNF-alpha-induced activation of NF-kappaB. PG490 also blocked TNF-alpha-mediated induction of c-IAP2 (hiap-1) and c-IAP1 (hiap-2), members of the inhibitor of apoptosis (IAP) family. Interestingly, PG490 did not block DNA binding of NF-kappaB, but it blocked transactivation of NF-kappaB. Our identification of a compound that blocks TNF-alpha-induced activation of NF-kappaB may enhance the cytotoxicity of TNF-alpha on tumors in vivo and limit its proinflammatory effects.
Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-kappaB transcriptional activation.[Pubmed:10224109]
J Biol Chem. 1999 May 7;274(19):13443-50.
PG490 (Triptolide) is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. PG490 inhibits interleukin(IL)-2 expression by normal human peripheral blood lymphocytes stimulated with phorbol 12-myristate 13-acetate (PMA) and antibody to CD3 (IC50 of 10 ng/ml), and with PMA and ionomycin (Iono, IC50 of 40 ng/ml). In Jurkat T-cells, PG490 inhibits PMA/Iono-stimulated IL-2 transcription. PG490 inhibits the induction of DNA binding activity at the purine-box/antigen receptor response element (ARRE)/nuclear factor of activated T-cells (NF-AT) target sequence but not at the NF-kappaB site. PG490 can completely inhibit transcriptional activation at the purine-box/ARRE/NF-AT and NF-kappaB target DNA sequences triggered by all stimuli examined (PMA, PMA/Iono, tumor necrosis factor-alpha). PG490 also inhibits PMA-stimulated activation of a chimeric transcription factor in which the C-terminal TA1 transactivation domain of NF-kappaB p65 is fused to the DNA binding domain of GAL4. In 16HBE human bronchial epithelial cells, IL-8 expression is regulated predominantly by NF-kappaB, and PG490 but not cyclosporin A can completely inhibit expression of IL-8. The mechanism of PG490 inhibition of cytokine gene expression differs from cyclosporin A and involves nuclear inhibition of transcriptional activation of NF-kappaB and the purine-box regulator operating at the ARRE/NF-AT site at a step after specific DNA binding.