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Purity: ≥98%
Tirbanibulin dihydrochloride (also known as KXO1 dihydrochloride and KX2-391 dihydrochloride) is a dual Src/tubulin inhibitor approved in 2020 for the treatment of actinic keratosis on the face or scalp.
| Targets |
Src HuH7 (GI50 = 9 nM); Src PLC/PRF/5 (IC50 = 13 nM); Src Hep3B (IC50 = 26 nM); Src HepG2 (IC50 = 60 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
The Src inhibitor tirbanibulin (KX2-391) targets the Src substrate pocket. 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 treated with tirbanibulin (KX2-391).
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| Cell Assay |
Hep3B, HepG2, PLC/PRF/5, Huh7, and other liver cell lines are frequently grown and kept in basal medium with 2% fetal bovine serum (FBS) at 37°C and 5% CO2. In each well of a 96-well plate, cells are seeded at 4.0×103/190 μL and 8.0×103/190 μL in basal medium containing 1.5% FBS. Before adding Tirbanibulin (KX2-391) at concentrations ranging from 6,564 to 0.012 nM in triplicates, these are cultured for an additional night at 37°C and 5% CO2. Three days are spent incubating treated cells. On day three, 10 μL of a 5-mg/mL 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) solution is added to each well, and the cells are incubated for four hours. 10% SDS is added to diluted HCl to dissolve the formazan product. The optical density is measured at 570 nm. Parallel experiments are conducted with Tirbanibulin (KX2-391) to compare its potency and activity. With GraphPad Prism 5 statistical software, growth inhibition curves, 50% inhibition concentration (GI50), and 80% inhibition concentration (GI80) are calculated. Both the optical density at wavelength of 570 nm (OD570) signal format and the normalized data representing the percentage of maximum response are reported.
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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]. |
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| References |
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| Molecular Formula |
C₂₆H₃₁CL₂N₃O₃
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| Molecular Weight |
504.45
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| Exact Mass |
503.174
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| Elemental Analysis |
C, 61.23; H, 5.96; Cl, 14.46; N, 8.57; O, 9.79
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| CAS # |
1038395-65-1
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| Related CAS # |
Tirbanibulin;897016-82-9;Tirbanibulin Mesylate;1080645-95-9
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| PubChem CID |
24989633
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.7
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
34
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| Complexity |
540
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CPTPOZGQCQXHJO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C26H29N3O3.2ClH/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;;/h1-11,20H,12-19H2,(H,28,30);2*1H
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| Chemical Name |
N-benzyl-2-[5-[4-(2-morpholin-4-ylethoxy)phenyl]pyridin-2-yl]acetamide;dihydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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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: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
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| 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 (4.96 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 (4.96 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 (4.96 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: 4% DMSO+30% PEG 300+ddH2O: 5 mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9824 mL | 9.9118 mL | 19.8236 mL | |
| 5 mM | 0.3965 mL | 1.9824 mL | 3.9647 mL | |
| 10 mM | 0.1982 mL | 0.9912 mL | 1.9824 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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