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Purity: ≥98%
Y15 (also known as FAK inhibitor Y15 and FAK Inhibitor 14) is a novel, potent, specific and direct inhibitor of focal adhesion kinase (FAK) which blocks phosphorylation of Y397 with an IC50 value of about 1 μM. In thyroid cancer cell lines, Y15 reduces viability, clonogenicity, and cell attachment while working in concert with targeted therapies. Y15 has been demonstrated to slow the growth of cancer both in vivo and in vitro. Y15 prevents tumor growth, lowers the viability of cancer cells, and inhibits its autophosphorylation activity.
| Targets |
FAK
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|---|---|
| ln Vitro |
Y15 treatment in vitro results in decreased cell viability, increased detachment, and increased apoptosis in colon cancer cells, breast cancer cells, and melanoma. Y15 dose-dependently inhibits the expression of total FAK and pY397 in TPC1, BCPAP, K1, and TT cell lines. All cell lines of thyroid cancer experience effective dose-dependent detachment. All medullary and papillary thyroid cancer cell lines exhibit an increase in necrosis, and all of them show a dose-dependent decrease in colony formation when exposed to Y15[1]. Y15 does not target homologous Pyk-2, c-Src, c-RAF, EGFR, IGFR, PDGFR, PI3K, VEGFR-3, and c-Met [3].
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| ln Vivo |
Y15 inhibits the growth of neuroblastoma, pancreatic, and breast tumors in vivo[2]. According to the pharmacokinetics study conducted on mice, Y15 is absorbed very quickly in these animals, with maximum plasma concentration being reached in 4.8 minutes after intraperitoneal administration at a dose of 30 mg/kg. With half-lives of 6.9 and 11.6 minutes, respectively, Y15 metabolizes quickly in mouse and human liver microsomes. Y15 has a maximum tolerated dose of 200 mg/kg for single-dose oral administration and a maximum tolerated dose of 100 mg/kg for multiple oral administration during a 7-day study. At 30 mg/kg by IP during the 28-day study and 100 mg/kg by PO during the 7-day study, Y15 does not result in any mortality or statistically significant changes in body weight. In various mouse organs, at 30 mg/kg by IP over 28 days and at 100 mg/kg dose by PO over 7 days, there are no clinical, chemical, hematological, or histopathological changes[3].
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| Enzyme Assay |
A kinase buffer containing 10 μCi of [γ-32P]-ATP A kinase buffer containing 10 μCi of [γ-32P]-ATP is incubated with 0.1 μg of purified FAK protein and 20 mM HEPES, pH 7.4, 5 mM MgCl2, 5 mM MnCl2, 0.1 mM Na3VO4. After the kinase reaction has been running for five minutes at room temperature, 2× Laemmli buffer is added to halt it. Proteins are separated using a Ready SDS-10% PAGE gel, and autoradiography is used to show the phosphorylated enolase.
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| Cell Assay |
Ten thousand cells per well, in 100 μL of medium containing 10% FBS and 1% penicillin/streptomycin, are seeded onto 96-well dishes. After the inhibitor treatment for twenty-four hours, each well receives 20 μL of Cell Titer 96 Aqueous One Solution Cell Proliferation Assay. At 490 nm, the plate is read following a two-hour reagent incubation period.
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| Animal Protocol |
Mice: Female, naked mice six weeks of age are employed. Athalic nude mice are given a subcutaneous injection of 5×106 Panc si5-IGF-1R cells, which have been mixed with matrigel, in their flank on day zero. By day seven, the animals are split into two groups at random. 30 mg/kg of Y15 was administered to one group (n = 5), while PBS was given to the other group (n = 5). Using 5×106 Panc si-ctrl cells combined with matrigel, subcutaneous injections are made into the flanks of naked mice to create Panc si-ctrl xenografts. On day 7, these animals are also split into two groups at random; five animals each group received TAE226 (30 mg/kg), while the other five animals received PBS as a control. Intraperitoneal injections of 0.1 mL in total volume are used to administer the medications and PBS. Beginning on day 10, tumor sizes are measured every three or four days in terms of length (mm) and width (mm). The formula to calculate the volume of a tumor is volume (cm3) = 1/2×length (cm)×width (cm)2.
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| References | |
| Additional Infomation |
Focal adhesion kinase (FAK) is up-regulated in thyroid cancer and small molecule FAK scaffolding inhibitor, Y15, was shown to decrease cancer growth in vitro and in vivo. We sought to test the effectiveness of Y15 in thyroid cancer cell lines, profile gene expression with Y15 compared with clinical trial FAK inhibitor PF-04554878, and use Y15 in novel drug combinations. Cell viability was decreased in a dose dependent manner in four thyroid cancer cell lines with Y15 and with higher doses in PF-04554878. Y397 FAK and total FAK were decreased with Y15 and decreased less with PF-04554878. Detachment and necrosis were increased in a dose-dependent manner in all cell lines with Y15. Clonogenicity was decreased in a dose-dependent manner for both Y15 and PF-04554878. We compared gene profiles between papillary thyroid cell lines, TPC1, BCPAP and K1, and 380, 109, and 74 genes were significantly >2-fold changed with Y15 treatment, respectively. Common up-regulated genes were involved in apoptosis, cell cycle, transcription and heat shock; down-regulated genes were involved in cell cycle, cell-to-cell interactions, and cancer stem cell markers. We also compared gene profiles of TT cells treated with Y15 versus PF-04554878. Y15 caused 144 genes to change over 4 fold and PF-04554878 caused 208 gene changes >4-fold (p<0.05). Among genes changed 4 fold, 11 were shared between the treatments, including those involved in metabolism, cell cycle, migration and transcription. Y15 demonstrated synergy with PF-04554878 in TT cells and also synergy with Cabozantinib, Sorafenib, Pazopanib, and strong synergy with Sunitinib in resistant K1 cells. This report revealed the biological effect of Y15 inhibitor, detected the unique and common gene signature profiles in response to Y15 in 4 different thyroid cancer cell lines, demonstrated differential response changes with Y15 and PF-04554878 treatment, and showed the synergy of Y15 with PF-04554878, Cabozantinib, Sorafenib, Pazopanib, and Sunitinib.[1]
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| Molecular Formula |
C6H14CL4N4
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|---|---|
| Molecular Weight |
284.0142
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| Exact Mass |
281.997
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| Elemental Analysis |
C, 25.37; H, 4.97; Cl, 49.93; N, 19.73
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| CAS # |
4506-66-5
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| Related CAS # |
4506-66-5 (HCl)
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| PubChem CID |
78260
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| Appearance |
Light green to green solid powder
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| Boiling Point |
400.9ºC at 760mmHg
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| Melting Point |
≥300ºC(lit.)
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| Flash Point |
233.6ºC
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| Index of Refraction |
1.827
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| LogP |
5.548
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
0
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| Heavy Atom Count |
14
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| Complexity |
90.3
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl[H].Cl[H].Cl[H].Cl[H].N([H])([H])C1C([H])=C(C(=C([H])C=1N([H])[H])N([H])[H])N([H])[H]
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| InChi Key |
BZDGCIJWPWHAOF-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C6H10N4.4ClH/c7-3-1-4(8)6(10)2-5(3)9;;;;/h1-2H,7-10H2;4*1H
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| Chemical Name |
benzene-1,2,4,5-tetramine;tetrahydrochloride
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| Synonyms |
FAK Inhibitor 14; FAK Inhibitor Y15; Y15 hydrochloride; Y15 tetrahydrochloride; 1,2,4,5-Benzenetetramine tetrahydrochloride; Benzene-1,2,4,5-tetraamine tetrahydrochloride; FAK Inhibitor 14; Y15; Benzene-1,2,4,5-tetramine 4HCl; 1,2,4,5-Tetraaminobenzene tetrahydrochloride; MFCD00012970; Y 15; Y-15.
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| HS Tariff Code |
292159
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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, 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) |
DMSO: 25~56 mg/mL (197.2~88.0 mM)
Water: ~56 mg/mL (~197.2 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (35.21 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5210 mL | 17.6050 mL | 35.2100 mL | |
| 5 mM | 0.7042 mL | 3.5210 mL | 7.0420 mL | |
| 10 mM | 0.3521 mL | 1.7605 mL | 3.5210 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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