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Triptolide Hsp90 mellandomäninhibitor

Name: Triptolide
Brand: Selleck Chemicals
SKU: S3604
Rating: 5 (47 reviews)

Kat.nr.: S3604

Triptolide är en diterpen triepoxid, immunsuppressivt medel extraherat från den kinesiska örten Tripterygium wilfordii. Den fungerar som en NF-κB-hämmare med dubbla åtgärder genom störning av p65/CBP-interaktion och genom minskning av p65-protein. Triptolide (PG490) upphäver transaktiveringsfunktionen hos heat shock transcription factor 1 (HSF1). Triptolide hämmar MDM2 och inducerar apoptos genom en p53-oberoende väg.

Triptolide ADC Cytotoxin Kemisk Chemical Structure

Kemisk struktur

Molekylvikt: 360.4

Hoppa till

Kvalitetskontroll (Quality Control)

Batch: Renhet: 99.95%

99.95

Relaterade mål	NF-κB HDAC Antioxidant ROS IκB/IKK Nrf2 AP-1 MALT NOD
Övrigt ADC Cytotoxin Inhibitorer	SN-38 Luteolin (+)-Bicuculline Rutin Artemisinin BHQ Pinocembrin Luteoloside Lappaconite HBr Gramine

Cellodling, behandling & arbetskoncentration
(Cell Culture, Treatment & Working Concentration)

Cellinjer	Analystyp	Koncentration	Inkubationstid	Aktivitetsbeskrivning	PMID
HT-29	Cytotoxicity against			Cytotoxicity against human HT-29 cells, IC50=0.0021μM	21470864
HCT116	Cytotoxicity against			Cytotoxicity against human HCT116 cells assessed as decrease in cell viability, IC50=0.0047μM	31121546
SKOV3	Antiproliferative activity against		72 hrs	Antiproliferative activity against human SKOV3 cells after 72 hrs by SRB assay, IC50=0.006μM	20833543
SKOV3	Cytotoxicity against		72 hrs	Cytotoxicity against human SKOV3 cells after 72 hrs by sulforhodamine B assay, IC50=0.006μM	24378709
SKOV3	Cytotoxic activity against		72 hrs	Cytotoxic activity against human SKOV3 cells assessed as reduction in cell viability after 72 hrs by SRB assay, IC50=0.0072μM	28011223
KBM5	Cytotoxicity against		72 hrs	Cytotoxicity against imatinib-resistant human KBM5 cells harboring Bcr-Abl T315I mutant after 72 hrs by MTS assay, IC50=0.0083μM	20149665
SKOV3	Cytotoxicity against			Cytotoxicity against human SKOV3 cells by SRB assay, IC50=0.009μM	19637874
MDA-MB-468	Cytotoxicity against			Cytotoxicity against human MDA-MB-468 cells by SRB assay, IC50=0.01μM	19637874
HCT116	Cytotoxicity against		72 hrs	Cytotoxicity against human HCT116 cells after 72 hrs by MTT assay, IC50=0.01μM	19637874
SKOV3	Cytotoxicity against		72 hrs	Cytotoxicity against human SKOV3 cells after 72 hrs by MTT assay, IC50=0.01μM	19637874
KBM5	Cytotoxicity against		72 hrs	Cytotoxicity against human KBM5 cells harboring wild type Bcr-Abl after 72 hrs by MTS assay, IC50=0.0103μM	20149665
Rh30	Cytotoxicity against		72 hrs	Cytotoxicity against human Rh30 cells after 72 hrs by MTT assay, IC50=0.014μM	19637874
A549	Antagonist activity at			Antagonist activity at human PAR2 expressed in human A549 cells assessed as inhibition of 2f-LIGRLO-NH2-induced NFkappaB activation by luciferase reporter gene assay, IC50=0.014μM	23895492
SGC7901	Cytotoxicity against		72 hrs	Cytotoxicity against human SGC7901 cells after 72 hrs by MTT assay, IC50=0.015μM	19637874
MOLT4	Cytotoxicity against		72 hrs	Cytotoxicity against human MOLT4 cells after 72 hrs by MTT assay, IC50=0.017μM	19637874
A549	Cytotoxic activity against		72 hrs	Cytotoxic activity against human A549 cells assessed as reduction in cell viability after 72 hrs by SRB assay, IC50=0.0175μM	28011223
SMMC7721	Cytotoxicity against		72 hrs	Cytotoxicity against human SMMC7721 cells after 72 hrs by MTT assay, IC50=0.018μM	19637874
PC3	Cytotoxic activity against		72 hrs	Cytotoxic activity against human PC3 cells assessed as reduction in cell viability after 72 hrs by SRB assay, IC50=0.0183μM	28011223
MCF7	Cytotoxicity against		72 hrs	Cytotoxicity against human MCF7 cells after 72 hrs by MTT assay, IC50=0.019μM	19637874
A549	Cytotoxicity against			Cytotoxicity against human A549 cells, IC50=0.019μM	21470864
PC3	Cytotoxicity against			Cytotoxicity against human PC3 cells by SRB assay, IC50=0.02μM	19637874
Bel7402	Cytotoxicity against		72 hrs	Cytotoxicity against human Bel7402 cells after 72 hrs by MTT assay, IC50=0.02μM	19637874
PC3	Antiproliferative activity against		72 hrs	Antiproliferative activity against human PC3 cells after 72 hrs by SRB assay, IC50=0.02μM	20833543
PC3	Cytotoxicity against		72 hrs	Cytotoxicity against human PC3 cells after 72 hrs by sulforhodamine B assay, IC50=0.02μM	24378709
PC3	Cytotoxicity against			Cytotoxicity against human PC3 cells assessed as inhibition of cell proliferation by sulforhodamine B assay, IC50=0.02μM	25467158
786-O	Cytotoxicity against		72 hrs	Cytotoxicity against human 786-O cells after 72 hrs by MTT assay, IC50=0.022μM	19637874
A549	Antagonist activity at			Antagonist activity at human PAR2 expressed in human A549 cells coexpressing TACR1 assessed as inhibition of substance P-induced IL-8 production by ELISA, IC50=0.023μM	23895492
MDA-MB-231	Cytotoxicity against		72 hrs	Cytotoxicity against human MDA-MB-231 cells after 72 hrs by MTT assay, IC50=0.024μM	19637874
DU145	Cytotoxicity against		72 hrs	Cytotoxicity against human DU145 cells after 72 hrs by MTT assay, IC50=0.024μM	19637874
HO8910	Cytotoxicity against		72 hrs	Cytotoxicity against human HO8910 cells after 72 hrs by MTT assay, IC50=0.028μM	19637874
HCT15	Cytotoxicity against		72 hrs	Cytotoxicity against human HCT15 cells after 72 hrs by MTT assay, IC50=0.029μM	19637874
A549	Growth inhibition of human			Growth inhibition of human A549 cells, IC50=0.03μM	28814374
32D	Cytotoxicity against		72 hrs	Cytotoxicity against mouse 32D cells harboring wild type Bcr-Abl after 72 hrs by MTS assay, IC50=0.032μM	20149665
U251	Cytotoxicity against			Cytotoxicity against human U251 cells assessed as inhibition of cell proliferation by sulforhodamine B assay, IC50=0.033μM	25467158
32D	Cytotoxicity against		72 hrs	Cytotoxicity against imatinib-resistant mouse 32D cells harboring Bcr-Abl T315I mutant after 72 hrs by MTS assay, IC50=0.034μM	20149665
PC3	Cytotoxicity against		72 hrs	Cytotoxicity against human PC3 cells after 72 hrs by MTT assay, IC50=0.043μM	19637874
KB	Cytotoxicity against		72 hrs	Cytotoxicity against human KB cells after 72 hrs by MTT assay, IC50=0.043μM	19637874
HepG2	Cytotoxicity against		48 hrs	Cytotoxicity against human HepG2 cells after 48 hrs by XTT assay, IC50=0.0433μM	30613335
HeLa	Cytotoxicity against		72 hrs	Cytotoxicity against human HeLa cells after 72 hrs by MTT assay, IC50=0.047μM	19637874
U251	Cytotoxicity against		72 hrs	Cytotoxicity against human U251 cells after 72 hrs by MTT assay, IC50=0.049μM	19637874
K562	Cytotoxicity against		72 hrs	Cytotoxicity against human K562 cells after 72 hrs by MTT assay, IC50=0.05μM	19637874
NIH/3T3	Cytotoxicity against			Cytotoxicity against mouse NIH/3T3 cells assessed as decrease in cell viability, IC50=0.05μM	31121546
SW1116	Cytotoxicity against		72 hrs	Cytotoxicity against human SW1116 cells after 72 hrs by MTT assay, IC50=0.052μM	19637874
A549	Cytotoxicity against		72 hrs	Cytotoxicity against human A549 cells after 72 hrs by MTT assay, IC50=0.059μM	19637874
HeLa	Cytotoxicity against			Cytotoxicity against human HeLa cells assessed as decrease in cell viability, IC50=0.087μM	31121546
Jurkat	Cytotoxicity against			Cytotoxicity against human Jurkat cells assessed as decrease in cell viability, IC50=0.14μM	31121546
MKN28	Cytotoxicity against		72 hrs	Cytotoxicity against human MKN28 cells after 72 hrs by MTT assay, IC50=0.2μM	19637874
MDCK	Cytotoxicity against			Cytotoxicity against MDCK cells assessed as decrease in cell viability, IC50=1.2μM	31121546
Pkd1-/-	Induction of			Induction of cell growth arrest in mouse Pkd1-/- cells in presence of calcium	17360534
Pkd1-/-	Increase in	100 nM	96 hrs	Increase in p21CIP/WAF expression in mouse Pkd1-/- cells at 100 nM after 96 hrs by Western blot analysis	17360534
Pkd1+/-	Increase in	100 nM		Increase in PC2 dependent calcium release in mouse Pkd1+/- cells at 100 nM	17360534
Pkd1-/-	Increase in	100 nM		Increase in PC2 dependent calcium release in mouse Pkd1-/- cells at 100 nM	17360534
Pkd1-/-	Increase in	50 uM		Increase in calcium release in mouse Pkd1-/- cells at 50 uM in presence of RyR antagonist dantrolene	17360534
Pkd2+/-	Growth inhibition of PC2 expressing mouse	100 nM	24 hrs	Growth inhibition of PC2 expressing mouse Pkd2+/- cells as cell death at 100 nM after 24 hrs	17360534
KBM5	Cytotoxicity against	0.001 to 17 uM	72 hrs	Cytotoxicity against human KBM5 cells harboring wild type Bcr-Abl at 0.001 to 17 uM after 72 hrs by MTS assay	20149665
KBM5	Cytotoxicity against	0.001 to 17 uM	72 hrs	Cytotoxicity against imatinib-resistant human KBM5 cells harboring Bcr-Abl T315I mutant at 0.001 to 17 uM after 72 hrs by MTS assay	20149665
LNCAP	Antagonist activity at	5 uM	24 hrs	Antagonist activity at AR in human LNCAP cells assessed as suppression of DHT-induced receptor transcriptional activity at 5 uM after 24 hrs by dual luciferase reporter gene assay	27994731
LNCAP	Antagonist activity at	500 nM	24 hrs	Antagonist activity at AR in human LNCAP cells assessed as suppression of DHT-induced receptor transcriptional activity at 500 nM after 24 hrs by dual luciferase reporter gene assay	27994731
HepG2	Antitumor activity against	0.2 mg/kg	15 days	Antitumor activity against human HepG2 cells xenografted in Balb/c nude mouse assessed as reduction in tumor growth at 0.2 mg/kg, ip administered once daily for 15 days	30613335
Klicka för att visa mer experimentella data för cellinjer

Kemisk information, lagring & stabilitet (Chemical Information, Storage & Stability)

Molekylvikt	360.4	Formel	C₂₀H₂₄O₆	Lagring (från mottagningsdatumet)	3 år-20°Cpulver
CAS-nr	38748-32-2	Ladda ner SDF		Lagring av stamlösningar	1 år-80°Ci lösningsmedel 1 månad-20°Ci lösningsmedel

Löslighet (Solubility)

In vitro
Batch:

DMSO : 72 mg/mL (199.77 mM)
(Fuktkontaminerad DMSO kan minska lösligheten. Använd färk, vattenfri DMSO.)

Water : Insoluble

Ethanol : Insoluble

Molaritetsräknare

Massa	Koncentration	Volym	Molekylvikt
=	×	×

Utspädningsräknare Molekylviktsräknare

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	2%DMSO 1 30%PEG300 2 2%Tween80 3 66%ddH2O Validerad av Selleck-laboratorier. Om du behöver justeringar av denna formulering, kontakta vårt säljteam för skräddarsydd testning.	3.000mg/ml (8.32mM)	Taking the 1 mL working solution as an example, add 20 μL of 150 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 20 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 660 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

In vivo-formuleringsräknare (Klar lösning)

Steg 1: Ange information nedan (Rekommenderas: Ett extra djur för att ta hänsyn till förluster under experimentet)

Dosering: mg/kg Djurens medelvikt: g Doseringsvolym per djur:μL Antal djur:

Steg 2: Ange in vivo-formuleringen (Detta är endast räknaren, inte formuleringen. Vänligen kontakta oss först om det inte finns någon in vivo-formulering i löslighetsavsnittet.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Beräkningsresultat:

Arbetskoncentration: mg/ml;

Metod för att bereda DMSO-stamlösning: mg substans förlöst i μL DMSO ( Stamlösningskoncentration mg/mL, Vänligen kontakta oss först om koncentrationen överskrider DMSO-lösligheten för denna batch av substansen. )

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedanμL PEG300, blanda och klarna, tillsätt sedanμL Tween 80, blanda och klarna, tillsätt sedan μL ddH₂O, blanda och klarna.

Metod för att bereda in vivo-formulering: Ta μL DMSO stamlösning, tillsätt sedan μL Majsolja, blanda och klarna.

Obs: 1. Se till att vätskan är klar innan du tillsätter nästa lösningsmedel.
2. Se till att tillsätta lösningsmedlet/lösningsmedlen i ordning. Du måste se till att lösningen som erhålls i föregående tillsats är en klar lösning innan du fortsätter att tillsätta nästa lösningsmedel. Fysiska metoder som vortex, ultraljud eller varmt vattenbad kan användas för att underlätta upplösningen.

Verkningsmekanism (Mechanism of Action)

Targets/IC₅₀/Ki	NF-κB HSF1 MDM2
In vitro	Triptolide is a diterpene triepoxide with potent immunosuppressive and antiinflammatory properties. This compound is shown to inhibit the expression of IL-2 in activated T cells at the level of purine-box/nuclear factor and NF-κB mediated transcription activation. It inhibits the proliferation and colony formation of tumor cells at extremely low concentrations (2–10 ng/mL). This chemical has an inhibitory activity on breast, stomach and leukemia cell line HL-60 cells. It induces apoptosis in tumor cells by blocking NF-κB activation and sensitizing tumor cells for TNF-&alpha induced programmed cell death.
In vivo	Triptolide synergizes with cyclosporin A in promoting graft survival in animal models and in suppression of graft versus host disease in allogeneic bone marrow transplants. In addition, it induces apoptosis in tumor cells and potentiates tumor necrosis factor (TNF-α) induction of apoptosis in part through the suppression of c-IAP2 and c-IAP1 induction. This compound treatment for 2–3 weeks inhibits the growth of xenografts formed by four different tumor cell lines (B16 melanoma, MDA-435 breast cancer, TSU bladder cancer, and MGC80-3 gastric carcinoma), indicating that TPL has a broad spectrum of activity against tumors that contain both wild-type and mutant forms of p53. In addition, it inhibits experimental metastasis of B16F10 cells to the lungs and spleens of mice. It has in vitro and in vivo activities against mouse models of polycystic kidney disease. LD50: Mice 0.83mg/kg (i.v.).
Referenser	[1] https://pubmed.ncbi.nlm.nih.gov/10224109/ [2] https://pubmed.ncbi.nlm.nih.gov/12533674/ [3] https://pubmed.ncbi.nlm.nih.gov/10224110/ [4] https://pubmed.ncbi.nlm.nih.gov/17360534/ [5] https://pubmed.ncbi.nlm.nih.gov/23583804/

Applikationer (Applications)

Metoder	Biomarkörer	Bilder	PMID
Western blot	c-Jun MDM2 p-AKT / AKT / p-Foxo3a / Foxo3a / p53 p-PI3K / PI3K / p85 / p110		22666381
Growth inhibition assay	Cell viability		22666381

C1=C0/X	C1:	LOG(C1):
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C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):