Name: Triciribine (API-2)
Brand: Selleck Chemicals
SKU: S1117
Rating: 5 (94 reviews)

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Batch: Zuiverheid: 99.70%

99.70

Gerelateerde doelwitten	PI3K mTOR GSK-3 ATM/ATR DNA-PK AMPK PDPK1 PTEN PP2A PDK
Overig Akt Inhibitoren	SC79 AZD5363 (Capivasertib) MK-2206 Dihydrochloride Ipatasertib (GDC-0068) Perifosine GSK690693 Afuresertib (GSK2110183) CCT128930 A-674563 HCl Akti-1/2

Celkweek, behandeling & werkzame concentratie

Cellijnen	Assaytype	Concentratie	Incubatietijd	Activiteitsbeschrijving	PMID
L1210	Function assay			Tested in vitro for cytotoxicity against murine L1210 leukemic cells, IC50=0.035μM	10882371
HFF	Function assay			HCMV plaque assay was performed using HFF cells and effect was calculated as a percentage of reduction in number of plaques, IC50=2.5μM	10882371
BSC-1	Antiviral assay			Antiviral activity was tested using an enzyme-linked immunosorbent assay (ELISA) to detect HSV-1 (herpes simplex virus type 1) using BSC-1 cells, IC50=23μM	10882371
HFF	Antiviral assay			Antiviral activity against HCMV was determined by plaque reduction assay using HFF cells, IC50=2.5μM	10882373
AA2	Function assay		5 hrs	Intracellular phosphorylation (100 uM) in uninfected AA2 cells was studied after 5 hrs of Incubation., Concentration=9μM	10882373
BSC-1	Antiviral assay			Antiviral activity against HSV-1 was determined using BSC-1 cells by an enzyme-linked immunosorbent assay (ELISA), IC50=23μM	10882373
Huh-7	Function assay			Compound was tested for its ability to inhibit hepatitis C viral RNA replication in Huh-7 cells (human hepatoma cells), EC50=2μM	15177464
MCF7	Cytotoxicity assay			Cytotoxicity against human MCF7 cells in presence of 20 uM chloroquine by SRB assay, GI50=0.05μM	18691894
MCF7	Cytotoxicity assay			Cytotoxicity against human MCF7 cells in presence of 10 uM chloroquine by SRB assay, GI50=0.56μM	18691894
MDA-MB-231	Cytotoxicity assay			Cytotoxicity against human MDA-MB-231 cells in presence of 20 uM chloroquine by SRB assay, GI50=0.69μM	18691894
MCF7	Cytotoxicity assay			Cytotoxicity against human MCF7 cells by SRB assay, GI50=3.64μM	18691894
MDA-MB-468	Cytotoxicity assay			Cytotoxicity against human MDA-MB-468 cells in presence of 20 uM chloroquine by SRB assay, GI50=10.29μM	18691894
184B5	Cytotoxicity assay	20 uM		Cytotoxicity against human 184B5 cells at 20 uM chloroquine by SRB assay, GI50=16.96μM	18691894
MDA-MB-468	Cytotoxicity assay	10 uM		Cytotoxicity against human MDA-MB-468 cells in presence of 10 uM chloroquine by SRB assay, GI50=20.45μM	18691894
184B5	Cytotoxicity assay	10 uM		Cytotoxicity against human 184B5 cells at 10 uM chloroquine by SRB assay, GI50=34μM	18691894
MDA-MB-231	Cytotoxicity assay	10 uM		Cytotoxicity against human MDA-MB-231 cells in presence of 10 uM chloroquine by SRB assay, GI50=37μM	18691894
184B5	Cytotoxicity assay			Cytotoxicity against human 184B5 cells by SRB assay, GI50=40μM	18691894
MDA-MB-468	Cytotoxicity assay			Cytotoxicity against human MDA-MB-468 cells by SRB assay, GI50=43.53μM	18691894
MDM	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 ADA infected in human MDM cells assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.006μM	20086149
ACH2	Cytotoxicity assay			Cytotoxicity against human ACH2 cells infected with latent Human immunodeficiency virus 1 by MTS assay, CC50=0.01μM	20086149
ACH2	Cytotoxicity assay			Cytotoxicity against human ACH2 cells infected with latent Human immunodeficiency virus 1 by MTS assay in presence of tumor necrosis factor alpha, CC50=0.01μM	20086149
CEM-SS	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 0.78 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.01μM	20086149
MDM	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 BAL infected in human MDM cells assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.018μM	20086149
H9	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 SK1 infected in human H9 cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.036μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B expressing nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.04μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 0.78 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.08μM	20086149
H9	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 25 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM	20086149
H9	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 12.5 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM	20086149
H9	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 6.25 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.1μM	20086149
H9	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 12.5 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.1μM	20086149
H9	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 6.25 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50<0.1μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 SK1 infected in human CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.13μM	20086149
ACH2	Antiviral assay		3 days	Antiviral activity against 5 x 10'3 cells/well Human immunodeficiency virus 1 infected in human ACH2 cells assessed as inhibition of viral Reverse transcriptase after 3 days by [3H]TTP incorporation assay in presence of 5 ng/ml tumor necrosis factor alpha, IC50=0.15μM	20086149
AA5	Antiviral assay			Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 3.13 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM	20086149
AA5	Antiviral assay			Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 1.56 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM	20086149
AA5	Antiviral assay			Antiviral activity against of Human immunodeficiency virus 1 3B infected in AA5 cells infected with 0.78 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50<0.17μM	20086149
CEM-SS	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 1.56 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.19μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 harboring plasmid NL4-3 infected in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.2μM	20086149
U1	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 infected in human U1 cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.23μM	20086149
CEM-SS	Antiviral assay		6 days	Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 3.13 uL of virus stock assessed as expression of p24 antigen after 6 days postinfection by ELISA, IC50=0.24μM	20086149
U1	Cytotoxicity assay			Cytotoxicity against human U1 cells infected with latent Human immunodeficiency virus 1 by MTS assay, CC50=0.28μM	20086149
U1	Cytotoxicity assay			Cytotoxicity against human U1 cells infected with latent Human immunodeficiency virus 1 by MTS assay in presence of tumor necrosis factor alpha, CC50=0.28μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 1.56 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.29μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human CEM-SS cells infected with 3.13 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.3μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 D1 harboring Tyr127His mutation in nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.33μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 A7 harboring Tyr127His mutation in nef protein infecting in CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=0.5μM	20086149
MDM	Cytotoxicity assay			Cytotoxicity against human MDM cells infected with Human immunodeficiency virus 1 BAL by MTS assay, TC50=0.66μM	20086149
CEM-SS	Antiviral assay			Antiviral activity against Human immunodeficiency virus 2 ROD infected in human CEM-SS cells assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=1.4μM	20086149
H9	Antiviral assay			Antiviral activity against Human immunodeficiency virus 1 3B infected in human H9 cells infected with 50 uL of virus stock assessed as inhibition of viral Reverse transcriptase by [3H]TTP incorporation assay, IC50=1.53μM	20086149
H9	Cytotoxicity assay			Cytotoxicity against human H9 cells by MTS assay, IC50=16.3μM	20086149
H9	Cytotoxicity assay			Cytotoxicity against human H9 cells by MTS assay, CC50=19.6μM	20086149
Klik om meer experimentele gegevens over cellijnen te bekijken

Chemische informatie, opslag en stabiliteit

Molecuulgewicht	320.3	Formule	C₁₃H₁₆N₆O₄	Opslag (vanaf de datum van ontvangst)	3 jaar-20°Cpoeder
CAS-nr.	35943-35-2	SDF downloaden		Opslag van stamoplossingen	1 jaar-80°Cin oplosmiddel 1 maand-20°Cin oplosmiddel
Synoniemen	NSC 154020, VD-0002, vqd-002, TCN			Smiles	CN1C2=NC=NC3=C2C(=CN3C4C(C(C(O4)CO)O)O)C(=N1)N

Oplosbaarheid

In vitro
Batch:

DMSO : 64 mg/mL (199.81 mM)
(Met vocht verontreinigd DMSO kan de oplosbaarheid verminderen. Gebruik verse, watervrije DMSO.)

Ethanol : 16 mg/mL

Water : Insoluble

Molariteitscalculator

Massa	Concentratie	Volume	Molecuulgewicht
=	×	×

Verdunningscalculator Molecuulgewichtcalculator

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.
Clear solution	2% DMSO 1 40% PEG 300 2 5%Tween80 3 53%ddH2O Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor aangepaste tests.	1.500mg/ml (4.68mM)	Taking the 1 mL working solution as an example, add 20 μL of 75 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 530 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.

In vivo formulatiecalculator (heldere oplossing)

Stap 1: Voer onderstaande informatie in (Aanbevolen: een extra dier om rekening te houden met verlies tijdens het experiment)

Dosering: mg/kg Gemiddeld gewicht van dieren: g Doseervolume per dier:μL Aantal dieren:

Stap 2: Voer de in vivo formulering in (Dit is alleen de calculator, geen formulering. Neem eerst contact met ons op als er geen in vivo formulering is in de sectie oplosbaarheid.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Berekeningsresultaten:

Werkconcentratie: mg/ml;

Methode voor het bereiden van DMSO-moedervloeistof: mg geneesmiddel vooropgelost in μL DMSO ( Concentratie moedervloeistof mg/mL, Neem eerst contact met ons op als de concentratie de DMSO-oplosbaarheid van de batch van het geneesmiddel overschrijdt. )

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toeμL PEG300, mengen en verhelderen, daarna toevoegenμL Tween 80, mengen en verhelderen, daarna toevoegen μL ddH₂O, mengen en verhelderen.

Methode voor het bereiden van in vivo formulering: Neem μL DMSO moedervloeistof, voeg daarna toe μL Maïsolie, mengen en verhelderen.

Opmerking: 1. Zorg ervoor dat de vloeistof helder is voordat u het volgende oplosmiddel toevoegt.
2. Zorg ervoor dat u het/de oplosmiddel(en) in de juiste volgorde toevoegt. U moet ervoor zorgen dat de verkregen oplossing, bij de vorige toevoeging, een heldere oplossing is voordat u verdergaat met het toevoegen van het volgende oplosmiddel. Fysieke methoden zoals vortexen, ultrasoon of een warmwaterbad kunnen worden gebruikt om het oplossen te bevorderen.

Werkingsmechanisme

Targets/IC₅₀/Ki	HIV-1 (CEM-SS, H9, H9IIIB, U1 cells) 20 nM Akt (PC3 cells) 130 nM
In vitro	Triciribine (API-2) vertoont maximale groeiremming rond 1-10 μM en remt de fosforylering van Akt, evenals stroomafwaartse p70S6K, tot basale niveaus bij 100 μM (IC50 = 130 nM). Het toont bijzondere belofte voor het remmen van groei in Nf1 en Trp53 mutante astrocytomacellen op een graadafhankelijke manier. De WHO II K1861-10 lijn wordt, onvolledig (69% maximale remming), geremd met een GI50-waarde van 1,7 μM voor deze verbinding, terwijl hoger-gradige tumorlijnen (KR158, KR130 en SF295) in grotere mate (>80% maximale remming) worden geremd bij lagere GI50-waarden (0,4-1,1 mM). Belangrijk is dat het veel minder effectief is in het remmen van primaire astrocyten (GI50 13,6 mM), wat suggereert dat deze remmer specificiteit kan vertonen voor tumorcellen. Het remt HIV-1 met een IC50 van 20 nM. Meer dan 90% remming wordt bereikt bij 0,1 μM en volledige remming van syncytia-vorming wordt bereikt bij 5 μM. Geassocieerde celtoxiciteit in dezelfde cellijn voor Triciribine is 46 μM, wat resulteert in selectiviteitsindices van 2250. Het remt significant HIV-1-geïnduceerde p24 kernantigeenproductie, reverse transcriptase en infectieuze virusproductie op een dosisafhankelijke manier met behulp van acuut geïnfecteerde CEM-SS, H9 en persistent geïnfecteerde H9III _B en U1 cellen met HIV-1. Deze verbinding remt Akt-fosforylering bij Thr308 en Ser473 en Akt-activiteit in de menselijke prostaatkankercellijn PC-3. Het sensibiliseert PC-3 cellen voor TRAIL- en anti-CD95-geïnduceerde apoptose, terwijl de cellen resistent blijven tegen DNA-beschadigende chemotherapeutica. Het is zeer selectief voor Akt en remt de activering van fosfatidylinositol 3-kinase, fosfoinositide-afhankelijke kinase-1, proteïnekinase C, serum- en glucocorticoïde-induceerbare kinase, proteïnekinase A, signaaltransducer en activatoren van transcriptie 3, extracellulair signaal-gereguleerde kinase-1/2 of c-Jun NH2-terminale kinase niet.
Kinase Assay	Akt Fosforylering Veranderingen Assay
Kinase Assay	Cellen worden gekweekt tot 80%–90% confluentie en gedurende 5–10 minuten gestimuleerd met 1–10 ng/mL epidermale groeifactor of bloedplaatjesafgeleide groeifactor (PDGF)–AA met of zonder 10–20 mM U0126 of LY-294002. Eiwitlysaten (5–20 μg) worden gescheiden door 12%–15% SDS PAGE en geanalyseerd met Western blot voor Akt, gefosforyleerd Akt (fosfo-Ser 473), MAPK en gefosforyleerd MAPK (p44/42 fosfo-Thr202/Tyr204) antilichamen (1:1000).
In vivo	Triciribine (API-2), toegediend met 1 mg/kg/dag i.p., remt de tumorgroei met 90%, 88% en 80% in naakte muizen met respectievelijk OVCAR3, OVCAR8 en PANC1 tumoren, die Akt overexpressen. Deze verbinding heeft echter weinig effect op de groei van OVCAR5 en COLO357 cellen.
Referenties	[1] https://pubmed.ncbi.nlm.nih.gov/21636709/ [2] https://pubmed.ncbi.nlm.nih.gov/7685612/ [3] https://pubmed.ncbi.nlm.nih.gov/19422047/ [4] https://pubmed.ncbi.nlm.nih.gov/15231645/

Toepassingen

Methoden	Biomarkers	Afbeeldingen	PMID
Western blot	PUMA / p-FoxO3a / p-AKT		20978166
Immunofluorescence	TRF2 / 53BP1		23862686

Informatie over klinische proeven

(gegevens van https://clinicaltrials.gov, bijgewerkt op 2024-05-22)

NCT-nummer	Werving	Aandoeningen	Sponsor/medewerkers	Startdatum	Fasen
NCT02987127	Unknown status	Mucosa-Associated Lymphoid Tissue Lymphoma	National Taiwan University Hospital	February 2016	--
NCT00642031	Completed	Hematologic Malignancies\|Leukemia	Prescient Therapeutics Ltd.\|VioQuest Pharmaceuticals	August 2006	Phase 1

Technische ondersteuning

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Tel: +1-832-582-8158 Ext:3

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Triciribine (API-2) Akt remmer

Chemische structuur

Molecuulgewicht: 320.3