Tirbanibulin

Catalog No.S2700 Batch:S270003

Technical Data

Formula

C₂₆H₂₉N₃O₃

Molecular Weight

431.53

CAS No.

897016-82-9

Solubility (25°C)*

In vitro

DMSO

86 mg/mL (199.29 mM)

Water

Insoluble

Ethanol

Insoluble

In vivo (Add solvents to the product individually and in order)

Clear solution

4%DMSO 1 30%PEG300 2 66%ddH2O

5.0mg/ml

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 means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

Biological Activity

Description

Tirbanibulin, the first clinical Src inhibitor (peptidomimetic class) that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines. Phase 2.

Targets

Src (HuH7) ^[1] (Cell-free assay)	Src (PLC/PRF/5) ^[1] (Cell-free assay)	Src (Hep 3B) ^[1] (Cell-free assay)	Src (Hep G2) ^[1] (Cell-free assay)
9 nM(GI50)	13 nM(GI50)	26 nM(GI50)	60 nM(GI50)

In vitro

KX2-391 is a Src inhibitor that is directed to the Src substrate pocket. KX2-391 shows steep dose-response curves against Huh7 (GI 50 = 9 nM), PLC/PRF/5 (GI 50 = 13 nM), Hep3B (GI 50 = 26 nM), and HepG2 (GI 50 = 60 nM), four hepatic cell cancer (HCC) cell lines. ^[1] KX2-391 is found to inhibit certain leukemia cells that are resistant to current commercially available drugs, such as those derived from chronic leukemia cells with the T3151 mutation. KX2-391 is evaluated in engineered Src driven cell growth assays inNIH3T3/c-Src527F and SYF/c-Src527F cells and exhibits GI50 with 23 nM and 39 nM, respectively. ^[2]

In vivo

In pre-clinical animal models of cancer, orally administered KX2-391 is shown to inhibit primary tumor growth and to suppress metastasis. ^[2]

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines Huh7, PLC/PRF/5, Hep3B, and HepG2 cell lines Concentrations 6,564 to 0.012 nM Incubation Time 3 days Method 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.

Cell Assay:^{^[1]}

Cell lines
Huh7, PLC/PRF/5, Hep3B, and HepG2 cell lines
Concentrations
6,564 to 0.012 nM
Incubation Time
3 days
Method
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.

References

Customer Product Validation

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

: Data from [Data independently produced by , , Front Immunol, 2018, 9:2433]

: Data from [Data independently produced by , , Oncotarget, 2016, 7(31):50027-50042]

: Data from [Data independently produced by , , Acta Pharmacol Sin, 2018, 39(8):1326-1337]

Selleck's Tirbanibulin has been cited by 40 publications

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
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
Targeting p130Cas- and microtubule-dependent MYC regulation sensitizes pancreatic cancer to ERK MAPK inhibition [ Cell Rep, 2021, 35(13):109291]	PubMed: 34192548

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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