Tirbanibulin

CatalogusnummerS2700 Batch:S270003

Afdrukken

Technische gegevens

Formule

C26H29N3O3
Moleculair gewicht 431.53 CAS-nr. 897016-82-9
Oplosbaarheid (25°C)* In vitro DMSO 86 mg/mL (199.29 mM)
Water Insoluble
Ethanol Insoluble
In vivo (Voeg oplosmiddelen afzonderlijk en in volgorde toe aan het product.)
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
4%DMSO 30%PEG300 66%ddH2O

Gevalideerd door Selleck labs. Mocht u aanpassingen aan deze formulering nodig hebben, neem dan contact op met ons verkoopteam voor maatwerktesten.

 5.000mg/ml (11.59mM) Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 300 μL of PEG 300, mix evenly to clarify it; 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. 
* <1 mg/ml betekent licht oplosbaar of onoplosbaar.
* Houd er rekening mee dat Selleck de oplosbaarheid van alle verbindingen intern test en de werkelijke oplosbaarheid enigszins kan afwijken van gepubliceerde waarden. Dit is normaal en is te wijten aan lichte batch-tot-batch variaties.
* Verzending op kamertemperatuur (Stabiliteitstests tonen aan dat dit product zonder koelmaatregelen kan worden verzonden.)

Voorbereiden van stamoplossingen

Biologische activiteit

Beschrijving Tirbanibulin, de eerste klinische Src-remmer (peptidomimetische klasse) die zich richt op de peptide-substraatplaats van Src, met een GI50 van 9-60 nM in kankercellijnen. Fase 2.
Doelen
Src (HuH7)
(Cell-free assay)		 Src (PLC/PRF/5)
(Cell-free assay)		 Src (Hep 3B)
(Cell-free assay)		 Src (Hep G2)
(Cell-free assay)
9 nM(GI50) 13 nM(GI50) 26 nM(GI50) 60 nM(GI50)
In vitro

KX2-391 is een Src-remmer die gericht is op de Src-substraatpocket. KX2-391 vertoont steile dosis-responscurves tegen Huh7 (GI 50 = 9 nM), PLC/PRF/5 (GI 50 = 13 nM), Hep3B (GI 50 = 26 nM) en HepG2 (GI 50 = 60 nM), vier hepatocellulaire carcinoom (HCC) cellijnen. KX2-391 blijkt bepaalde leukemiecellen te remmen die resistent zijn tegen momenteel commercieel verkrijgbare geneesmiddelen, zoals die afkomstig zijn van chronische leukemiecellen met de T3151-mutatie. KX2-391 wordt geëvalueerd in gemanipuleerde Src-gestuurde celgroeitests in NIH3T3/c-Src527F- en SYF/c-Src527F-cellen en vertoont GI50 met respectievelijk 23 nM en 39 nM.

In vivo

In preklinische diermodellen van kanker is aangetoond dat oraal toegediend KX2-391 de primaire tumorgroei remt en metastase onderdrukt.

Protocol (uit referentie)

Celassay:

[1]
  • Cellijnen

    Huh7, PLC/PRF/5, Hep3B, and HepG2 cell lines

  • Concentraties

    6,564 to 0.012 nM

  • Incubatietijd

    3 days

  • Methode

    Liver cell lines including Huh7, PLC/PRF/5, Hep3B, and HepG2 (NutriCyte, Buffalo, NY) are routinely cultured and maintained in basal medium containing 2% fetal bovine serum (FBS) at 37 °C and 5% CO2. Cells are seeded at 4.0 × 103/190 μL and 8.0 × 103/190 μL per well of 96-well plate in basal medium containing 1.5% FBS. These are cultured overnight at 37 °C and 5% CO2 prior to the addition of KX2-391, at concentrations ranging from 6,564 to 0.012 nM in triplicates. Treated cells are incubated for 3 days. Ten microliters of 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution (5 mg/mL) is then added to each well on day 3 and cells incubated for 4 hours. The formazan product is dissolved with 10% SDS in dilute HCl. Optical density at 570 nm is measured by using BioTek Synergy HT multiplatform microplate reader. For comparison of activity and potency, parallel experiments are performed using KX2-391. Growth inhibition curves, 50% inhibition concentration (GI50), and 80% inhibition concentration (GI80) are determined using GraphPad Prism 5 statistical software. Data are normalized to represent percentage of maximum response as well as reported in optical density at wavelength of 570 nm (OD570) signal format.

Referenties

  • https://pubmed.ncbi.nlm.nih.gov/18979199/
  • https://pubmed.ncbi.nlm.nih.gov/21852023/

Klantproductvalidatie

<p>Images of typical cultures treated with the compounds and/or 500 pM BoNT/A. Cells were treated with the compounds for 30 min and then intoxicated with 500 pM BoNT/A for 4 h. Cells were then fixed and immunostained for neuron-specific b-III Tubulin (green) and Hoechst dye (nuclei; blue).</p>

, , Neurotox Res, 2015, 27(4):384-98.

The histogram represents the absolute cell numbers obtained after 15 days of culture, in the presence of KX2-391 inhibitor at different concentrations and Dasatinib, as compared to control, arbitrarily normalized to one. The data are represented as mean±SEM obtained by nine independent experiments and analyzed by Wilcoxon signed-rank test (*p < 0.05; **p < 0.005).

Gegevens van [ , , Front Immunol, 2018, 9:2433 ]

(A) MDA-pc3, and MDA-B6 cells were cultured in glass-bottom plates in the presence of 25 nM KX2-391 or DMSO for 72 h and stained with 2.7 µg/mL propidium iodide (PI) in phenol red-free medium. Stained cells were imaged at 200 x magnification using Zeiss LSM 700 confocal microscope and PI-stained cells were counted in at least 10 randomly captured frames. Counts of PI-positive cells were normalized on the total cell numbers in matching frames. The graph shows the ratio of PI-positive cells in KX2-391-treated populations relative to matching DMSO controls.

Gegevens van [ , , Oncotarget, 2016, 7(31):50027-50042 ]

MDA-MB-231 cells were treated with KX2-391 for 12 h followed by immunoblotting analysis. Densitometric data (fold) were shown below each group.

Gegevens van [ , , Acta Pharmacol Sin, 2018, 39(8):1326-1337 ]

Sellecks Tirbanibulin Is geciteerd door 41 Publicaties

S1PR3-driven positive feedback loop sustains STAT3 activation and keratinocyte hyperproliferation in psoriasis [ Cell Death Dis, 2025, 16(1):31] PubMed: 39833165
Src/FN1 pathway activation drives tumor cell cluster formation and metastasis in lung cancer: A promising therapeutic target [ Sci Adv, 2025, 11(28):eadv7377] PubMed: 40632865
Tirbanibulin (KX2-391) analog KX2-361 inhibits botulinum neurotoxin serotype A mediated SNAP-25 cleavage in pre- and post-intoxication models in cells [ Drug Dev Res, 2024, 85(6):e22248] PubMed: 39166850
Anti-tumor effects of tirbanibulin in squamous cell carcinoma cells are mediated via disruption of tubulin-polymerization [ Arch Dermatol Res, 2024, 316(7):341] PubMed: 38847867
Tumor Cell-Intrinsic CD96 Mediates Chemoresistance and Cancer Stemness by Regulating Mitochondrial Fatty Acid β-Oxidation [ Adv Sci (Weinh), 2023, 10(7):e2202956] PubMed: 36581470
THY1 (CD90) Maintains the Adherens Junctions in Nasopharyngeal Carcinoma via Inhibition of SRC Activation [ Cancers (Basel), 2023, 15(7)2189] PubMed: 37046850
Intracellular CYTL1, a novel tumor suppressor, stabilizes NDUFV1 to inhibit metabolic reprogramming in breast cancer [ Signal Transduct Target Ther, 2022, 7(1):35] PubMed: 35115484
Systematic identification of biomarker-driven drug combinations to overcome resistance [ Nat Chem Biol, 2022, 10.1038/s41589-022-00996-7] PubMed: 35332332
Procr functions as a signaling receptor and is essential for the maintenance and self-renewal of mammary stem cells [ Cell Rep, 2022, 38(12):110548] PubMed: 35320720
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726

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NIET VOOR HUMANE, VETERINAIRE DIAGNOSTISCHE OF THERAPEUTISCHE DOELEINDEN.