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Purity: ≥98%
Tirbanibulin Mesylate (also known as KXO-1 Mesylate and KX2-391 Mesylate) is a tubulin/Src inhibitor that received FDA approval in 2020 to treat scalp or facial actinic keratosis
Targets |
Src, in HuH7 cells (GI50 = 9 nM); Src, in PLC/PRF/5 cells (IC50 = 13 nM);
Src, in Hep3B cells (IC50 = 26 nM); Src, in HepG2 cells (IC50 = 60 nM) |
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ln Vitro |
Tirbanibulin Mesylate, also known as KX2-391 Mesylate, is a substrate-specific Src inhibitor. The hepatic cell cancer (HCC) cell lines Huh7 (GI50=9 nM), PLC/PRF/5 (GI50=13 nM), Hep3B (GI50=26 nM), and HepG2 (GI50=60 nM) exhibit steep dose-response curves when exposed to tirbanibulin (KX2-391)[1]. It has been discovered that tirbanibulin mesylate (KX2-391 mesylate) inhibits some leukemia cells, such as those derived from chronic leukemia cells with the T3151 mutation, that are resistant to currently available commercial drugs. In NICH3T3/c-Src527F and SYF/c-Src527F cells, tirbanibulin mesylate (KX2-391 mesylate) is assessed in engineered Src driven cell growth assays and displays GI50 values of 23 nM and 39 nM, respectively[2].
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ln Vivo |
Tirbanibulin Mesylate (KX2-391 Mesylate), when taken orally, has been demonstrated in pre-clinical animal models of cancer to inhibit the growth of primary tumors and to suppress metastasis[2].
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Enzyme Assay |
Tirbanibulin (KX2-391) is a Src inhibitor that targets the substrate pocket of Src.
Tirbanibulin (KX2-391) exhibits sharp dose-response curves for four hepatic cell cancer (HCC) cell lines: Hep3B (GI50=26 nM), HepG2 (GI50=60 nM), PLC/PRF/5 (GI50=13 nM), and Huh7 (GI50=9 nM). |
Cell Assay |
Regularly cultured and maintained in basal medium containing 2% fetal bovine serum (FBS) at 37°C and 5% CO2, liver cell lines such as Huh7, PLC/PRF/5, Hep3B, and HepG2 (NutriCyte, Buffalo, NY) are used. 1.5% FBS-containing basal medium is used to seed cells at 4.0×103/190 μL and 8.0×103/190 μL per well of a 96-well plate. KX2-391, at concentrations ranging from 6,564 to 0.012 nM in triplicates, is added after these are cultivated for an additional night at 37°C and 5% CO2. Incubation lasts three days for treated cells. Day 3 then sees the addition of 10 microliters of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution (5 mg/mL) to each well, followed by a 4-hour incubation period. With 10% SDS in diluted HCl, the formazan product is dissolved. Using a BioTek Synergy HT multiplatform microplate reader, optical density at 570 nm is discovered. Parallel experiments using KX2-391 are carried out for comparison of potency and activity. A statistical program called GraphPad Prism 5 is used to calculate growth inhibition curves, 50% inhibition concentration (GI50), and 80% inhibition concentration (GI80). The data are presented in the optical density at wavelength of 570 nm (OD570) signal format and normalized to represent the percentage of maximum response.
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Animal Protocol |
Mouse bearing MDA-MB-231 tumors; Oral gavage; 1, 5mg/kg dose
Xenograft procedures and KX-01 oral dosing were as described (11). Briefly, mammary fat pad tumors were established by injecting 5×106 MDA-MB-231 cells in 150μl of PBS-Matrigel mixture (1:2) orthotopically and bilaterally into the mammary fat pads of female NUDE mice (two tumors/mouse). Treatments were started when tumors reached ∼80-100mm3. The first study used MDA-MB-231 xenografts and was performed using vehicle (ultra-pure water) and two doses of KX-01 (1, 5mg/kg) administered twice/day (BID) by oral gavage (using metal 22g feeding needle) for 28 days. A similar experiment was performed with MDA-MB-157 xenografts (another ER/PR/HER2 negative model) to assess KX-01 response. A second study was performed to test combination of KX-01 with paclitaxel on tumor growth. MDA-MD-231 tumor xenograft bearing mice were treated with vehicle or KX-01 (5mg/kg) BID, paclitaxel by intraperitoneal injection (IP) once/week, or combination of KX-0+paclitaxel. Treatments were for 40 days for all groups. A third study used MDA-MB-157 xenografts with the same combination treatment. A fourth study tested the effect of KX-01 or combination with paclitaxel for 24 days on larger MDA-MB-231 tumors (∼300mm3). Tumors were allowed to reach ∼300mm3 before beginning treatments. In this experiment mice were treated with KX-01 at a higher dose of 15mg/kg, and mice were treated once/day instead of twice/day. Paclitaxel was used at a dose of 20mg/kg IP once/week. In all experiments, tumor caliper measurements were taken twice/week and tumor volume was by calculated by the formula: 0.523×LM2 (where L-large diameter, M-small diameter). At the end the experiments animals were sacrificed and tumors and mouse organs removed. Tissues were either stored in 10% neutral buffered formalin for paraffin embedding, or snap frozen for measurement of chromosome-17 by real-time PCR, and embedded for frozen sectioning for CD-31 staining. Immunohistochemistry (IHC) was performed as described on paraffin-embedded tumor tissues [3]. |
References |
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Molecular Formula |
C27H33N3O6S
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Molecular Weight |
527.63
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Exact Mass |
527.20900695
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Elemental Analysis |
C, 61.46; H, 6.30; N, 7.96; O, 18.19; S, 6.08
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CAS # |
1080645-95-9
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Related CAS # |
1080645-95-9 (mesylate); 897016-82-9; 1038395-65-1 (HCl)
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Appearance |
White to off-white solid powder
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tPSA |
126Ų
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SMILES |
CS(=O)(=O)O.C1COCCN1CCOC2=CC=C(C=C2)C3=CN=C(C=C3)CC(=O)NCC4=CC=CC=C4
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InChi Key |
JGSYRKUPDSSTCB-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C26H29N3O3.CH4O3S/c30-26(28-19-21-4-2-1-3-5-21)18-24-9-6-23(20-27-24)22-7-10-25(11-8-22)32-17-14-29-12-15-31-16-13-29;1-5(2,3)4/h1-11,20H,12-19H2,(H,28,30);1H3,(H,2,3,4)
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Chemical Name |
N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide;methanesulfonic acid
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Synonyms |
KXO1 HCl; KX-01, KX 01 HCl; KXO1 HCl; Mesylate; KX-01, KX 01 Mesylate; KX2-391; KX-2-391 Mesylate; KX 2-391; KX2391; KX-2391; KX 2391 Mesylate
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HS Tariff Code |
2934.99.03.00
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.74 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: Formulation 1: ≥ 5 mg/mL (9.5 mM) in 4% DMSO+30% PEG 300+ddH2O Formulation 2: ≥ 2.5 mg/mL (4.7 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + + 45% Saline For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 25 mg/mL of DMSO stock solution and add tO + 400 μL of PEG300, mix well (clear solution); Then add 50 μL of Tween 80 to the above solution, mix well (clear solution); Finally, add 450 μL of saline to the above solution, mix well (clear solution). Preparation of saline: Dissolve 0.9 g sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Formulation 3: ≥ 2.5 mg/mL (4.7 mM) in 10% DMSO + 90% (20% SBE-β-CD in saline) For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 25 mg/mL of DMSO stock solution and add to 900 μL of 20% SBE-β-CD in saline, mix well (clear solution). Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Formulation 4: ≥ 2.5 mg/mL (4.7 mM) in 10% DMSO + 90% Corn oil For example, if 1 mL of working solution is to be prepared, you can take 100 μL of 25 mg/mL of DMSO stock solution and add to 900 μL of corn oil, mix well (clear solution). |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.8953 mL | 9.4763 mL | 18.9527 mL | |
5 mM | 0.3791 mL | 1.8953 mL | 3.7905 mL | |
10 mM | 0.1895 mL | 0.9476 mL | 1.8953 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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