(5R)-5-Hydroxytriptolide
Based on 1 Customer Validation
(5R)-5-Hydroxytriptolide (PG 701) is an orally active, CNS-penetrant NF-κB and TLR4 inhibitor. (5R)-5-Hydroxytriptolide suppresses IκB degradation, NF-κB nuclear translocation, inhibits NO release and pro-inflammatory cytokine expression. (5R)-5-Hydroxytriptolide upregulates Tp53 transcription, induces p53-mediated apoptosis. (5R)-5-Hydroxytriptolide can be used for the research of cerebral ischemia/reperfusion injury, non-small cell lung cancer brain metastasis, and rheumatoid arthritis.
For research use only. We do not sell to patients.
- Purity : 99.67%
- CAS No.: 583028-68-6
- Formula: C20H24O7
- Molecular Weight:376.40
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
0.04 nM
Compound: 7; LLDT-8
|
Cytotoxicity against human A549 cells assessed as decrease in cell viability after 72 hrs by MTT assay
Cytotoxicity against human A549 cells assessed as decrease in cell viability after 72 hrs by MTT assay
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[PMID: 31121546] |
| BGC-823 | IC50 |
1.5 μM
Compound: 7; LLDT-8
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Cytotoxicity against human BGC823 cells assessed as decrease in cell viability by MTT assay
Cytotoxicity against human BGC823 cells assessed as decrease in cell viability by MTT assay
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[PMID: 31121546] |
| HeLa | IC50 |
0.34 μM
Compound: 7; LLDT-8
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Cytotoxicity against human HeLa cells assessed as decrease in cell viability by MTT assay
Cytotoxicity against human HeLa cells assessed as decrease in cell viability by MTT assay
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[PMID: 31121546] |
| HL-60 | IC50 |
0.04 nM
Compound: 7; LLDT-8
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Cytotoxicity against human HL60 cells assessed as decrease in cell viability after 72 hrs by MTT assay
Cytotoxicity against human HL60 cells assessed as decrease in cell viability after 72 hrs by MTT assay
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[PMID: 31121546] |
| HL-60 | IC50 |
0.47 μM
Compound: 7; LLDT-8
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Cytotoxicity against human HL60 cells assessed as decrease in cell viability by MTT assay
Cytotoxicity against human HL60 cells assessed as decrease in cell viability by MTT assay
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[PMID: 31121546] |
| KB | IC50 |
0.3 μM
Compound: 7; LLDT-8
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Cytotoxicity against human KB cells assessed as decrease in cell viability by MTT assay
Cytotoxicity against human KB cells assessed as decrease in cell viability by MTT assay
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[PMID: 31121546] |
| MCF7 | IC50 |
0.04 nM
Compound: 7; LLDT-8
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Cytotoxicity against human MCF7 cells assessed as decrease in cell viability after 72 hrs by MTT assay
Cytotoxicity against human MCF7 cells assessed as decrease in cell viability after 72 hrs by MTT assay
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[PMID: 31121546] |
| MCF7 | IC50 |
1.05 μM
Compound: 7; LLDT-8
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Cytotoxicity against human MCF7 cells assessed as decrease in cell viability by MTT assay
Cytotoxicity against human MCF7 cells assessed as decrease in cell viability by MTT assay
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[PMID: 31121546] |
| MKN-28 | IC50 |
0.04 nM
Compound: 7; LLDT-8
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Cytotoxicity against human MKN28 cells assessed as decrease in cell viability after 72 hrs by MTT assay
Cytotoxicity against human MKN28 cells assessed as decrease in cell viability after 72 hrs by MTT assay
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[PMID: 31121546] |
| P388 | IC50 |
0.04 nM
Compound: 7; LLDT-8
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Cytotoxicity against mouse P388 cells assessed as decrease in cell viability after 72 hrs by MTT assay
Cytotoxicity against mouse P388 cells assessed as decrease in cell viability after 72 hrs by MTT assay
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[PMID: 31121546] |
| PC-3 | IC50 |
0.275 μM
Compound: 4
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Cytotoxicity against human PC3 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
Cytotoxicity against human PC3 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
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[PMID: 25467158] |
| U-251 | IC50 |
0.488 μM
Compound: 4
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Cytotoxicity against human U251 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
Cytotoxicity against human U251 cells assessed as inhibition of cell proliferation by sulforhodamine B assay
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[PMID: 25467158] |
In Vitro
(5R)-5-Hydroxytriptolide (LLDT-8) (50-400 nM; 24 h) dose-dependently inhibits LPS (HY-D1056)-induced NO production in mouse BV-2 microglial cells[1].
(5R)-5-Hydroxytriptolide (50-150 nM; 6 h) dose-dependently suppresses LPS-induced iNOS, IL-1β, and TNF-α mRNA expression in mouse BV-2 microglial cells[1].
(5R)-5-Hydroxytriptolide (50-150 nM; 24 h) dose-dependently attenuates LPS-induced TNF-α protein production in mouse BV-2 microglial cells at concentrations from 50 nM to 150 nM over 24 h[1].
(5R)-5-Hydroxytriptolide (50-150 nM; 24 h) dose-dependently inhibits LPS-induced NO production in mouse primary microglial cells, without reducing cell viability[1].
(5R)-5-Hydroxytriptolide (50-150 nM; 12-48 h) at 150 nM suppresses LPS-induced iNOS and TLR4 protein expression at 48 h and dose-dependently inhibits LPS-induced IκBα phosphorylation at 24 h in mouse BV-2 microglial cells[1].
(5R)-5-Hydroxytriptolide (150 nM) partially inhibits LPS-induced NF-κB (p65) nuclear translocation in mouse BV-2 microglial cells[1].
(5R)-5-Hydroxytriptolide (40-400 nM; 24-72 h) dose-dependently inhibits the proliferation of parental A549 and brain-metastatic A549-BrM2 cells[2].
(5R)-5-Hydroxytriptolide (40 nM; 7-14 days) reduces colony formation of parental A549 and brain-metastatic A549-BrM2 cells[2].
(5R)-5-Hydroxytriptolide (24 h) modulates gene expression in brain-metastatic A549-BrM2 cells, suppressing proliferation-associated pathways including DNA replication and cell cycle, and upregulates Tp53 without robustly inducing its negative regulator Mdm2[2].
(5R)-5-Hydroxytriptolide (200-400 nM) dose-dependently modulates cell cycle regulatory proteins (Cyclin-B1, Cyclin-D1, p27) in parental A549 and brain-metastatic A549-BrM2 cells, disrupting cell cycle progression[2].
(5R)-5-Hydroxytriptolide (200-400 nM) selectively induces p53 protein accumulation in brain-metastatic A549-BrM2 cells (but not parental A549 cells) and modulates apoptosis-related proteins (BAX, Bcl-2) in both cell lines to promote apoptosis[2].
(5R)-5-Hydroxytriptolide (200-400 nM; 24 h) dose-dependently induces apoptosis in parental A549 and brain-metastatic A549-BrM2 cells in vitro, with a stronger effect in BrM2 cells[2].
(5R)-5-Hydroxytriptolide potently suppresses multiple in vitro immune responses, including mitogen-induced T and B cell proliferation, mixed lymphocyte reaction, and inflammatory/Th1 type cytokine release[4].
(5R)-5-Hydroxytriptolide (12.5-50 nM; 6 day) decreases RANKL/M-CSF-induced formation of TRAP-positive osteoclast-like cells in RAW264.7 cells[5].
(5R)-5-Hydroxytriptolide (50 nM; 4 h pre-incubation) inhibits RANKL-induced phosphorylation of IκB, but not p38, JNK, ERK, or Akt, in RAW264.7 cells[5].
(5R)-5-Hydroxytriptolide suppresses IFN-γ production in concanavalin A or Sac-stimulated murine spleen cells in vitro[6].
(5R)-5-Hydroxytriptolide (48 h) exhibits low cytotoxicity in murine splenic lymphocytes, with a CC50 of 256.6 nM after 48 h incubation[7].
(5R)-5-Hydroxytriptolide (48 h) inhibits ConA-induced proliferation of murine splenic lymphocytes with an IC50 of 131.7 nM after 48 h incubation[7].
(5R)-5-Hydroxytriptolide (48 h) inhibits LPS-induced proliferation of murine splenic lymphocytes with an IC50 of 171.5 nM after 48 h incubation[7].
(5R)-5-Hydroxytriptolide (96 h) inhibits mixed lymphocyte reaction proliferation of murine splenic lymphocytes with an IC50 of 38.8 nM after 96 h total incubation[7].
(5R)-5-Hydroxytriptolide (25-100 nM; 24 h) dose-dependently reduces ConA-induced IL-2, IFN-γ, IL-4, and IL-6 production in BALB/c splenic lymphocytes after 24 h incubation at 25, 50, and 100 nM[7].
(5R)-5-Hydroxytriptolide (25-100 nM; 24 h) dose-dependently reduces Sac-induced IFN-γ and TNF-α production in BALB/c splenic lymphocytes after 24 h incubation at 25, 50, and 100 nM, with no effect on IL-12p40 or IL-10 production[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:mouse BV-2 microglial cells
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Concentration:50; 100; 150 nM
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Incubation Time:6 h
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Result:Dose-dependently inhibited LPS-induced mRNA expression of iNOS, IL-1β, and TNF-α.
Significantly reduced expression at 50 nM.
Caused a greater reduction at 100 nM.
Caused the strongest reduction at 150 nM, with significant differences compared to LPS-only treatment at each concentration.
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Cell Line:mouse BV-2 microglial cells
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Concentration:50; 100; 150 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced LPS-induced TNF-α protein production.
Significantly inhibited TNF-α protein production at 150 nM.
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Cell Line:mouse BV-2 microglial cells
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Concentration:50; 100; 150 nM
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Incubation Time:12 h, 24 h, 48 h
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Result:Significantly reduced LPS-induced iNOS protein levels at 48 h at 150 nM.
Reduced LPS-induced TLR4 protein levels at 48 h at 150 nM.
Inhibited LPS-induced p-IκBα levels at 24 h in a dose-dependent manner, with significant inhibition observed at 150 nM.
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Cell Line:Murine RAW264.7 cells
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Concentration:50 nM
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Incubation Time:4 h (pre-incubation); 0, 10, 30, 60 min (RANKL induction)
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Result:Markedly inhibited the RANKL-induced increase in phosphorylated IκB (p-IκB) levels across all time points tested.
Showed no significant effects on RANKL-induced phosphorylated p38, JNK, ERK, or Akt levels.
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Cell Line:BALB/c splenic lymphocytes
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Concentration:25; 50; 100 nM
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Incubation Time:24 h
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Result:Dose-dependently reduced ConA-induced production of IL-2, IFN-γ, IL-4, and IL-6.
Dose-dependently reduced Sac-induced production of IFN-γ and TNF-α, but had no apparent effect on IL-12p40 or IL-10 production.
In Vivo
(5R)-5-Hydroxytriptolide (1 mg/kg; i.p.; every other day; 24 days) inhibits non-small cell lung cancer brain metastasis growth in nude mice[2].
(5R)-5-Hydroxytriptolide (0.5-2 mg/kg; daily; 1 week) attenuates collagen-induced arthritis in rats in a dose-dependent manner[3].
(5R)-5-Hydroxytriptolide (1 mg/kg/day; p.o.; daily; until end of experiment) prevents graft-versus-host disease in a murine allogeneic bone marrow transplantation model, extending survival to >60 days for most treated mice[4].
(5R)-5-Hydroxytriptolide (0.5-2 mg/kg; i.p.; daily; 7 or 14 consecutive days) dose-dependently protects against Bleomycin (HY-17565)-induced lung fibrosis in mice[6].
(5R)-5-hydroxytriptolide (0.4-1000 μg/kg; i.p., p.o.; two doses: 1 h pre-challenge and 12 h post-challenge) dose-dependently suppresses DNFB-induced delayed-type hypersensitivity in female BALB/c mice, achieving a maximum 43.3% reduction in ear swelling at 1000 μg/kg p.o[7].
(5R)-5-hydroxytriptolide (40-1000 μg/kg; i.p., p.o.; daily; 4 days) dose-dependently inhibits SRBC-induced humoral immune responses in BALB/c mice[7].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR mice (male, 25-30 g, middle cerebral artery occlusion with monofilament technique, 1 h occlusion followed by reperfusion)[1]
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Dosage:0.5 mg/kg; 1 mg/kg
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Administration:i.p.; single dose immediately post-reperfusion
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Result:Significantly reduced infarct volumes in the cortex, striatum, and whole hemisphere (with edema correction) compared to vehicle.
Remarkably attenuated cortical tissue mRNA expression of TNF-α, iNOS, and IL-1β in the ischemic penumbra 24 h after reperfusion.
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Animal Model:nude mice (female, 5-6 weeks)[2]
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Dosage:1 mg/kg
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Administration:i.p.; every other day; 24 days
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Result:Showed a dramatic reduction in tumor radiance compared to vehicle controls by day 45.
Significantly reduced the proportion of Ki67-positive tumor cells compared to vehicle controls.
Significantly down-regulated Ki67 expression intensity compared to vehicle controls.
Caused no obvious weight loss, abnormal behavior, organ weight alterations, or histopathological abnormalities in heart, liver, spleen, lung, or kidney.
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Animal Model:Sprague-Dawley (male, weight 260 g)[3]
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Dosage:0.5 mg/kg; 1 mg/kg; 2 mg/kg
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Administration:daily; 1 week
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Result:Significantly reduced clinical arthritis scores in a dose-dependent manner at 1 mg/kg and 2 mg/kg doses.
Significantly suppressed collagen-induced increases in IL-1β and IL-6 at 1 mg/kg and 2 mg/kg doses.
Reduced iNOS protein expression at 1 mg/kg and 2 mg/kg doses.
Reduced MMP-13 protein expression at 1 mg/kg and 2 mg/kg doses.
Increased OPG gene expression at 1 mg/kg and 2 mg/kg doses.
Decreased RANKL gene expression at 1 mg/kg and 2 mg/kg doses.
Increased the OPG/RANKL ratio at 1 mg/kg and 2 mg/kg doses.
Inhibited RANKL-induced NF-κB expression at 1 mg/kg and 2 mg/kg doses.
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Animal Model:C57BL/6 (H-2b) (male, 8 to 10 weeks of age, allo-BMT model with 8.5 Gy total body irradiation prior to intravenous injection of BALB/c bone marrow and splenocytes)[4]
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Dosage:1 mg/kg/day
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Administration:p.o.; daily; until end of experiment
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Result:Extended survival of majority of treated mice to >60 days, whereas vehicle-treated mice died within 40 days.
Showed inconspicuous weight loss compared to vehicle-treated mice.
Maintained complete/near-complete donor chimerism in splenocytes.
Induced T cell unresponsiveness to donor (H-2d) and host (H-2b) antigens while preserving responsiveness to ConA.
Reduced spontaneous, ConA-stimulated, and host antigen-stimulated IFN-γ levels on day 7 post-transplantation.
Normalized CD4+/CD8+ T cell ratio to 1.16, 1.18, 0.74, and 1.08 on days 7, 14, 21, and 28 post-transplantation, respectively.
Increased Foxp3 mRNA expression in splenocytes on day 14 post-transplantation.
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Animal Model:C57BL/6 (female, 6-8 weeks old, 20-22 g, bleomycin-induced lung fibrosis)[6]
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Dosage:0.5 mg/kg; 1 mg/kg; 2 mg/kg
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Administration:i.p.; daily; 7 or 14 consecutive days
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Result:Dose-dependently attenuated bleomycin-induced body weight loss and inhibited increases in lung index on days 7 and 14.
Markedly reduced lung inflammation and fibrosis on day 14, with no obvious fibrotic foci in the 2 mg/kg group.
Dose-dependently reduced total cells, neutrophils, and lymphocytes in bronchoalveolar lavage fluid.
Reduced lung hydroxyproline levels.
Enhanced lung superoxide dismutase (SOD) activity.
Inhibited lung malondialdehyde production.
Suppressed pro-inflammatory and pro-fibrotic cytokine production.
Dose-dependently reduced transforming growth factor-β (TGF-β) levels, with 2 mg/kg returning TGF-β to near normal control levels on both days 7 and 14.
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Animal Model:BALB/c (female, 6 to 8 weeks old, DNFB-sensitized delayed-type hypersensitivity model)[7]
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Dosage:0.4 μg/kg (i.p.); 4 μg/kg (i.p.); 40 μg/kg (i.p., p.o.); 200 μg/kg (p.o.); 1000 μg/kg (p.o.)
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Administration:i.p.; two doses (1 h pre-challenge and 12 h post-challenge); p.o.; two doses (1 h pre-challenge and 12 h post-challenge)
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Result:Reduced ear swelling to 17.7 mg, 15.3 mg, and 17.1 mg at i.p. doses of 0.4 μg/kg, 4 μg/kg, and 40 μg/kg, respectively.
Reduced ear swelling to 33.8 mg, 30.0 mg, and 24.1 mg at p.o. doses of 40 μg/kg, 200 μg/kg, and 1000 μg/kg, respectively.
Achieved dose-dependent suppression of 20.5%, 29.5%, and 43.3% at p.o. doses of 40 μg/kg, 200 μg/kg, and 1000 μg/kg, respectively.
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Animal Model:BALB/c (6 to 8 weeks old, 8 mice per group, SRBC-immunized humoral immune response model)[7]
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Dosage:40 μg/kg (i.p., p.o.); 200 μg/kg (i.p., p.o.); 1000 μg/kg (i.p., p.o.)
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Administration:i.p.; daily; 4 days; p.o.; daily; 4 days
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Result:Reduced SRBC hemolysis to 0.175 OD, 0.162 OD, and 0.158 OD at i.p. doses of 40 μg/kg, 200 μg/kg, and 1000 μg/kg, respectively.
Suppressed hemolysis by 24.0% at 1000 μg/kg i.p.
Reduced SRBC hemolysis to 0.236 OD, 0.342 OD, and 0.240 OD at p.o. doses of 40 μg/kg, 200 μg/kg, and 1000 μg/kg, respectively.
Suppressed hemolysis by 36.3% at 1000 μg/kg p.o.
- Cytoplasmic-Nuclear Fractionated Protein Extraction
- RNA extraction experimental
- Collagen-Induced Arthritis
- Detection of Apoptosis
- TUNEL staining for apoptotic DNA fragmentation
- Annexin V plus membrane-impermeant dye apoptosis staining
- Apoptosis Solutions
- Research Protocol for Inflammation-related Diseases
- Orthotopic Cell-Line Xenograft
Chemical Information
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CAS No. 583028-68-6
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Appearance Solid
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Molecular Weight 376.40
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Formula C20H24O7
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Color White to off-white
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SMILES
CC([C@@]12[C@H]([C@H]3[C@]4([C@@]5(C)CCC6=C(COC6=O)[C@]5(O)C[C@H]7[C@@]4(O7)[C@@H]2O)O3)O1)C
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Synonyms
PG 701; LLDT-8; 5α-Hydroxytriptolide
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Purity & Documentation
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Data Sheet (317 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
(5R)-5-Hydroxytriptolide Related Classifications
HY-107101 Related Classifications
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Keywords
- (5R)-5-Hydroxytriptolide
- 583028-68-6
- PG 701
- LLDT-8
- 5α-Hydroxytriptolide
- PG701
- PG-701
- LLDT8
- LLDT 8
- LLDT-8
- IFNAR
- CD74
- JNK
- Interleukin Related
- TNF Receptor
- NF-κB
- HIV
- NO Synthase
- Apoptosis
- Interferon-α/β receptor
- Interferon-alpha/beta receptor
- HLA-DR-gamma
- Invariant polypeptide of major histocompatibility complex, class II antigen-associated
- c-Jun N-terminal kinase
- IL
- Tumor Necrosis Factor Receptor
- TNFR
- Nuclear factor-κB
- Nuclear factor-kappaB
- Human immunodeficiency virus
- Nitric oxide synthases
- NOS
- RAW264.7 cells
- A549-BrM2 cells
- cerebral ischemia/reperfusion injury
- A549 cells
- rheumatoid arthritis
- non-small cell lung cancer brain metastasis
- TLR4
- mouse BV-2 microglial cells
- CD4+CD25+ regulatory T cells
- Inhibitor
- inhibitor
- inhibit