Structure of Triptonide
CAS No.: 38647-11-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Triptonide, a natural product isolated and purified from the herb of Tripterygium wilfordii Hook.f. with antileukemic, antitumor, anti-inflammatory activities, is effective in the treatment of autoimmune diseases. Triptonide can effectively inhibit canonical Wnt/β-catenin signaling by targeting the downstream C-terminal transcription domain of β-catenin or a nuclear component associated with β-catenin.
Synonyms: PG 492; NSC 165677
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CAS No. : | 38647-11-9 |
Formula : | C20H22O6 |
M.W : | 358.39 |
SMILES Code : | O=C1OCC2=C1CC[C@@]3(C)[C@@]2([H])C[C@H]4[C@@]5(O4)C([C@]6(C(C)C)[C@@H](O6)[C@H]7[C@]53O7)=O |
Synonyms : |
PG 492; NSC 165677
|
MDL No. : | MFCD00210566 |
InChI Key : | SWOVVKGLGOOUKI-ZHGGVEMFSA-N |
Pubchem ID : | 65411 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
In Vitro:
Cell Line
|
Concentration | Treated Time | Description | References |
THP-1 cells | 1, 5, 10, 20 ng/ml | 1, 6, 12, 18 hours | To investigate the effect of Triptonide on IL-37 mRNA expression. Results showed that 20 ng/ml of Triptonide upregulated IL-37 mRNA expression approximately 3.2-fold after 12 hours of incubation. | Cell Mol Immunol. 2015 Jul;12(4):515-8 |
Rat intestine | 3–9 μg/mL | 10 minutes | Evaluate the absorption characteristics of Triptonide in rat intestine, showing that its absorption extent and rate were independent of concentration. | Chin Med. 2018 Jan 8;13:1 |
THP-1 cells | 20 ng/ml | 16 hours | To investigate the effect of Triptonide on IL-37 protein expression. Results showed that 20 ng/ml of Triptonide upregulated IL-37 protein expression approximately 3.4-fold after 16 hours of incubation. | Cell Mol Immunol. 2015 Jul;12(4):515-8 |
ARPE-19 cells | 10-100 nM | 24 hours | To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM. | Int J Mol Med. 2024 Sep;54(3):76 |
Müller cells (MIO-M1) | 10-100 nM | 24 hours | To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM. | Int J Mol Med. 2024 Sep;54(3):76 |
Human retinal capillary endothelial cells (HRCECs) | 10-100 nM | 24 hours | To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM. | Int J Mol Med. 2024 Sep;54(3):76 |
Human umbilical vein endothelial cells (HUVECs) | 10-100 nM | 24 hours | To evaluate the effect of Triptonide on cell viability, results showed no significant impact on cell viability at concentrations below 100 nM. | Int J Mol Med. 2024 Sep;54(3):76 |
RKO cells | 5 nM | 24 hours | Did not block BIO-induced β-catenin nuclear translocation | Sci Rep. 2016 Sep 6;6:32779 |
HEK293 cells | 5 nM | 24 hours | Did not affect Wnt3a-CM-induced β-catenin levels | Sci Rep. 2016 Sep 6;6:32779 |
SKBR3 | 0.2 µM | 24, 48, 72 hours | Inhibits cell growth | Sci Rep. 2021 Jan 28;11(1):2408 |
MCF7 | 0.2 µM | 24, 48, 72 hours | Inhibits cell growth | Sci Rep. 2021 Jan 28;11(1):2408 |
MDA-MB-231 | 0.2 µM | 24, 48, 72 hours | Inhibits TNBC cell growth | Sci Rep. 2021 Jan 28;11(1):2408 |
BT549 | 0.2 µM | 24, 48, 72 hours | Inhibits TNBC cell growth | Sci Rep. 2021 Jan 28;11(1):2408 |
HCC1806 | 0.2 µM | 24, 48, 72 hours | Inhibits TNBC cell growth and induces apoptosis | Sci Rep. 2021 Jan 28;11(1):2408 |
U-2OS cells | 5, 10, 25, 50, 100, 250 and 1000 nM | 48 hours | TN inhibited the proliferation of U-2OS cells in a dose-dependent manner with an IC50 of 97.2 nM | Cancer Manag Res. 2020 Jul 17;12:5919-5929 |
MG63 cells | 5, 10, 25, 50, 100, 250 and 1000 nM | 48 hours | TN inhibited the proliferation of MG63 cells in a dose-dependent manner with an IC50 of 108.6 nM | Cancer Manag Res. 2020 Jul 17;12:5919-5929 |
BT-549 | 0–320 nM | 70 hours | Inhibited TNBC cell proliferation with an IC50 of 12.1 nM. | Breast Cancer Res. 2021 Dec 18;23(1):116 |
SW480 cells | 16.8 nM (IC50) | 72 hours | Induced apoptosis | Sci Rep. 2016 Sep 6;6:32779 |
MDA-MB-468 | 0–320 nM | 70 hours | Inhibited TNBC cell proliferation with an IC50 of 14.4 nM. | Breast Cancer Res. 2021 Dec 18;23(1):116 |
MDA-MB-231 | 0–320 nM | 70 hours | Inhibited TNBC cell proliferation with an IC50 of 15.6 nM. | Breast Cancer Res. 2021 Dec 18;23(1):116 |
Pancreatic cancer cell Panc1 | 8 nM | 72 hours | Inhibited the LXR-SREBF1-PNKP signaling pathway, increased DNA strand breaks, and induced apoptosis | Cell Death Differ. 2020 Aug;27(8):2433-2450 |
Pancreatic cancer cell Patu8988 | 8 nM | 72 hours | Inhibited the LXR-SREBF1-PNKP signaling pathway, increased DNA strand breaks, and induced apoptosis | Cell Death Differ. 2020 Aug;27(8):2433-2450 |
ST2 cells | 10 nM | 72 hours | Triptonide blocks the Wnt signaling pathway by binding to the C-terminal transactivation domain of β-catenin, thereby inhibiting C91-induced osteoblast differentiation in ST2 cells. | Front Endocrinol (Lausanne). 2022 Jul 18;13:926622 |
In Vivo:
Species
|
Animal Model
|
Administration | Dosage | Frequency | Description | References |
Cynomolgus monkeys | Adult male C57BL/6J and CD-1 mice, adult male cynomolgus monkeys | Oral | 0.1 mg/kg | Mice: once daily for 3-4 weeks; Monkeys: once daily for 5-6 weeks | To evaluate the efficacy and safety of Triptonide as a male contraceptive. Results showed that Triptonide induced sperm deformation and loss of motility, leading to male infertility within 3-4 weeks (mice) and 5-6 weeks (monkeys), with no discernable systematic toxic side effects. | Nat Commun. 2021 Feb 23;12(1):1253 |
Mice | Adult male C57BL/6J and CD-1 mice, adult male cynomolgus monkeys | Oral | 0.8 mg/kg | Mice: once daily for 3-4 weeks; Monkeys: once daily for 5-6 weeks | To evaluate the efficacy and safety of Triptonide as a male contraceptive. Results showed that Triptonide induced sperm deformation and loss of motility, leading to male infertility within 3-4 weeks (mice) and 5-6 weeks (monkeys), with no discernable systematic toxic side effects. | Nat Commun. 2021 Feb 23;12(1):1253 |
C57BL/6 male mice | Light-induced and N-Methyl-D-aspartic acid (NMDA)-induced retinal injury models | Intravitreal injection | 2 µl of Tn (1 mg/ml) | Single injection, lasting 7 days | To evaluate the protective effect of Triptonide on light-induced and NMDA-induced retinal injury, results showed that Triptonide pretreatment significantly improved retinal function and structure and inhibited choroidal neovascularization. | Int J Mol Med. 2024 Sep;54(3):76 |
NOD-SCID female mice | TNBC MDA-MB-231 xenograft model | Intraperitoneal injection | 3 mg/kg | Once daily for 95 days | Suppressed TNBC tumor growth and lung metastasis with a tumor inhibitory rate of 98%. | Breast Cancer Res. 2021 Dec 18;23(1):116 |
Sprague-Dawley rats | Single-pass intestinal perfusion model | Intestinal perfusion | 3–9 μg/mL | Single perfusion, lasting 80 minutes | Evaluate the absorption characteristics of Triptonide in rat intestine, showing that its absorption extent and rate were independent of concentration. | Chin Med. 2018 Jan 8;13:1 |
Nude mice | MDA-MB-231 xenograft model | Oral gavage | 5 mg/kg | Once daily for 17 days | Inhibits xenograft tumor growth | Sci Rep. 2021 Jan 28;11(1):2408 |
Nude mice | Pancreatic cancer Patu8988 xenograft model | Intraperitoneal injection | 5 mg/kg/d | Once daily for 73 days | Inhibited tumor growth, with complete elimination of tumors in five out of eight xenograft mice and an overall inhibition rate of 99.6% | Cell Death Differ. 2020 Aug;27(8):2433-2450 |
Tags: Triptonide | NSC 165677 | PG 492 | NSC165677 | NSC-165677 | PG492 | PG 492 | PG-492 | Wnt signalling pathway | β-catenin | Apoptosis | Autophagy | Beta catenin | Tripterygium | wilfordii | Hook F. | lymphoma | anti-cancer | Lyn | ERK | inhibitor | 38647-11-9 |
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