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| 25mg |
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Purity: ≥98%
YM201636, a pyridofuropyrimidine compound, is a novel, potent and selective PIKfyve (phosphatidylinositol‑3‑phosphate 5‑kinase) inhibitor with potential anti-retroviral replication and anticancer activity, as silencing of PIKfyve which is the sole enzyme for PtdIns(3,5)P(2) biosynthesis that controls proper endosome dynamics, can inhibit retroviral replication. YM-201636 has an IC50 of 33 nM and inhibits PIKfyve. At 800 nM, YM 201636 can prevent retroviral budding, suggesting that it may be useful as an antiretroviral therapeutic agent [1,2]. By enhancing EGFR expression, YM201636 may also inhibit the growth of liver tumors [3].
| Targets |
PIKfyve (IC50 = 33 nM); p110α (IC50 = 3.3 μM)
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|---|---|
| ln Vitro |
YM201636 exhibits about 100-fold selectivity for PtdIns3P p110α with an IC50 of 3 μM while potently inhibiting the mammalian PIKfyve with an IC50 of 33 nM but not the yeast orthologue Fab1. In serum-starved NIH3T3 cells followed by serum stimulation, YM201636 (0.8 μM) significantly reduces PtdIns(3,5)P2 production by 80% while having no impact on Ser 473 phosphorylation of protein kinase B (PKB) in response to serum stimulation. By inhibiting the production of PIKfyve and PtdIns(3,5)P2, YM-201636 reversibly impairs endosomal trafficking in NIH3T3 cells, simulating the effects of siRNA-mediated PIKfyve depletion. Additionally, YM-201636 (0.8 μM) significantly reduces the number of retroviruses that can budding from cells by 80%, presumably by interfering with the ESCRT machinery. [1] In 3T3L1 adipocytes, YM-201636 has an IC50 of 54 nM and almost completely inhibits basal and insulin-activated 2-deoxyglucose uptake at doses as low as 160 nM. It has also been demonstrated that YM-201636 (0.1 M) completely inhibits the insulin-dependent activation of class IA PI 3-kinase.[2] YM201636 (0.4 μM) significantly lowers the invasive abilities of NPM-ALK-expressing cells and their capacity to degrade the extracellular matrix, even though it is not involved in NPM-ALK-dependent proliferation and migration. [3] In MDCK cells, YM201636 treatment prevents junctional proteins claudin-1 and claudin-2 from recycling continuously, delaying the formation of the epithelial barrier and causing intracellular accumulation. [4]
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| Enzyme Assay |
Following 3T3L1 adipocyte serum-starvation and insulin stimulation, cell lysates containing protease inhibitors are clarified and then subjected to immunoprecipitation with anti-PIKfyve antibodies. Washed beads are mixed with 100 μM PtdIns and preincubated for 15 min with YM-201636 (100 nM) or vehicle in the assay buffer (50 mM Tris-HCl, pH 7.5, 1 mM EGTA and 10 mM MgCl2). The kinase assay (50 μL final volume) is carried out for 15 min at 37 °C with 15 μM ATP and [γ-32P]ATP (30 μCi). Lipids are extracted, spotted on TLC glass plates (250 μm), resolved by a chloroform/methanol/water/ammonia solvent system and detected by autoradiography[2].
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| Cell Assay |
YM-201636 is dissolved in DMSO and diluted with DMEM and added to cells at a final concentration of 800 nM. YM-201636 or a DMSO control is applied to cells for 2 hours. 0.4 µm pore size Transwell permeable polyester filters with a surface area of 0.33 cm2 are used for TER measurements when cells are plated at confluency. Cells are grown for 7 days before TER measurements[4], with media changes occurring every 2-3 days.
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| References |
| Molecular Formula |
C25H21N7O3
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|---|---|
| Molecular Weight |
467.4793
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| Exact Mass |
467.17059
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| Elemental Analysis |
C, 64.23; H, 4.53; N, 20.97; O, 10.27
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| CAS # |
371942-69-7
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| Related CAS # |
371942-69-7
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| Appearance |
White to off-white solid powder
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| SMILES |
C1COCCN1C2=NC(=NC3=C2OC4=C3C=CC=N4)C5=CC(=CC=C5)NC(=O)C6=CN=C(C=C6)N
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| InChi Key |
YBPIBGNBHHGLEB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H21N7O3/c26-19-7-6-16(14-28-19)24(33)29-17-4-1-3-15(13-17)22-30-20-18-5-2-8-27-25(18)35-21(20)23(31-22)32-9-11-34-12-10-32/h1-8,13-14H,9-12H2,(H2,26,28)(H,29,33)
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| Chemical Name |
6-amino-N-[3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenyl]pyridine-3-carboxamide
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| Synonyms |
YM-201636; YM201636; YM 201636
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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 |
| 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: ~35 mg/mL (~74.9 mM)
Water: <1 mg/mL Ethanol: <1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.35 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 (5.35 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (5.35 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1391 mL | 10.6956 mL | 21.3913 mL | |
| 5 mM | 0.4278 mL | 2.1391 mL | 4.2783 mL | |
| 10 mM | 0.2139 mL | 1.0696 mL | 2.1391 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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The specific inhibition of in vivo PtdIns(3,5)P2 production by YM201636. EMBO Rep, 2008, 9(2), 164-170. |
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