| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
YM-254890 targets Gαq/11 proteins, a family of heterotrimeric G proteins that couple to Gq-coupled receptors. It selectively inhibits Gαq/11-mediated signaling with an IC50 of 0.15 μM in P2Y2-C6-15 cells. The compound blocks Gαq/11-coupled ADP receptor P2Y1-mediated Ca²⁺ mobilization and inhibits ADP-induced platelet aggregation.
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| ln Vitro |
With IC50 values of 0.37, 0.39, and 0.51 μM, YM-254890 suppresses platelet aggregation in human platelet-rich plasma that is triggered by ADP (2, 5, and 20 μM). Platelet aggregation is mediated by ADP via the G protein-coupled receptors P2Y1 and P2Y12. C6-15 cells that transiently expressed human P2Y1 or P2Y12 receptors were used to investigate the effects of YM-254890 on the P2Y1 and P2Y12 signaling pathways. When 2MeSADP is used to stimulate P2Y1-C6-15 cells, there is a greater intracellular calcium mobilization. With an IC50 value of 0.031 μM, YM-254890 suppresses the rise in [Ca2+]i in this experiment. On the other hand, in P2Y12-C6-15 cells, YM-254890 at 40 μM had no effect on the 2MeSADP-induced suppression of forskolin-stimulated adenylyl cyclase activity [1].
In vitro, YM-254890 inhibits ADP-induced intracellular calcium elevation with an IC50 of 0.92±0.28 μM. It inhibits 2MeSADP-stimulated calcium mobilization in P2Y1-C6-15 cells with an IC50 of 0.031 μM. At 40 μM, it does not affect 2MeSADP-induced inhibition of forskolin-stimulated adenylyl cyclase in P2Y12-C6-15 cells, demonstrating selectivity for Gq over Gi-coupled pathways. U46619-induced platelet aggregation is inhibited by YM-254890, but phorbol ester- or ionophore-induced aggregation is not. |
| ln Vivo |
In vivo, YM-254890 has demonstrated the ability to inhibit Gq-mediated signaling in animal models. As a Gαq/11 inhibitor, it blocks downstream signaling pathways involved in platelet aggregation and other Gq-mediated cellular responses. The compound's in vivo activity has been characterized in models of thrombosis and hemostasis.
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| Enzyme Assay |
For receptor signaling assays, cells expressing Gq-coupled receptors (e.g., P2Y1) are loaded with calcium-sensitive dyes. YM-254890 is pre-incubated with cells, and receptor activation is induced by agonists (e.g., 2MeSADP). Intracellular calcium mobilization is measured using fluorescence-based assays to determine IC50 values for inhibition.
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| Cell Assay |
Cellular assays utilize C6-15 cells stably expressing human P2Y1 or P2Y12 receptors. Cells are treated with YM-254890 at various concentrations (0.001-40 μM) and then stimulated with 2MeSADP. Calcium mobilization is measured in P2Y1-expressing cells, while inhibition of forskolin-stimulated cAMP accumulation is measured in P2Y12-expressing cells.
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| Animal Protocol |
In vivo studies are typically conducted in rodent models of thrombosis or platelet aggregation. YM-254890 is administered intravenously or intraperitoneally, and platelet aggregation is measured ex vivo or in vivo. Endpoints include inhibition of ADP-induced platelet aggregation and assessment of bleeding time. Gq-mediated signaling in other tissues may also be evaluated.
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| ADME/Pharmacokinetics |
YM-254890 (molecular weight 960.08) is a macrocyclic peptide with membrane permeability, a unique property for a peptide-based inhibitor. It is soluble in DMSO (30 mg/mL, 31.25 mM). For in vivo administration, the compound can be formulated in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline.
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| Toxicity/Toxicokinetics |
Preclinical toxicity studies of YM-254890 have been limited, as the compound is primarily used as a research tool. As a Gαq/11 inhibitor, its toxicity profile is related to the inhibition of Gq-mediated signaling pathways. No significant toxicity has been reported at concentrations used for in vitro and in vivo studies.
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| References |
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| Additional Infomation |
YM-254890 is a selective Gαq/11 inhibitor discovered from microbial sources. Its mechanism involves blocking the activation of Gαq/11 proteins, thereby inhibiting Gq-coupled receptor signaling and downstream effectors such as PLCβ and calcium mobilization. The compound is a valuable research tool for studying Gq-mediated signaling in platelets, cardiovascular system, and other tissues.
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| Molecular Formula |
C46H69N7O15
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|---|---|
| Molecular Weight |
960.077973127365
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| Exact Mass |
959.485
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| CAS # |
568580-02-9
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| Related CAS # |
568580-02-9 (YM-254890); 1702378-78-6 ( WU-07047, a simplified analog of the selective Gαq/11 inhibitor YM-25489) |
| PubChem CID |
9919454
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
1232.4±65.0 °C at 760 mmHg
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| Flash Point |
699.1±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.560
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| LogP |
-1.84
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
68
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| Complexity |
1870
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| Defined Atom Stereocenter Count |
11
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| SMILES |
C[C@@H]1[C@@H](C(=O)O[C@@H](C(=O)N(C(=C)C(=O)N[C@H](C(=O)N([C@H](C(=O)N[C@H](C(=O)N([C@H](C(=O)O1)[C@@H](C)OC)C)[C@@H](C(C)C)OC(=O)[C@H]([C@@H](C(C)C)O)NC(=O)C)C)C)C)C)CC2=CC=CC=C2)NC(=O)C
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| InChi Key |
QVYLWCAYZGFGNF-WBWCVGBTSA-N
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| InChi Code |
InChI=1S/C46H69N7O15/c1-22(2)37(56)34(49-30(11)55)45(63)68-38(23(3)4)35-43(61)53(14)36(28(9)65-15)46(64)66-27(8)33(48-29(10)54)44(62)67-32(21-31-19-17-16-18-20-31)42(60)52(13)25(6)39(57)47-24(5)41(59)51(12)26(7)40(58)50-35/h16-20,22-24,26-28,32-38,56H,6,21H2,1-5,7-15H3,(H,47,57)(H,48,54)(H,49,55)(H,50,58)/t24-,26-,27+,28+,32+,33-,34-,35-,36-,37+,38+/m0/s1
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| Chemical Name |
(R)-1-((3S,6S,9S,12S,18R,21S,22R)-21-Acetamido-18-benzyl-3-((R)-1-methoxyethyl)-4,9,10,12,16,22-hexamethyl-15-methylene-2,5,8,11,14,17,20-heptaoxo-1,19-dioxa-4,7,10,13,16-pentaazacyclodocosan-6-yl)-2-methylpropyl (2S,3R)-2-acetamido-3-hydroxy-4-methylpentanoate
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| Synonyms |
YM254890; YM 254890; YM-254890
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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 : ~50 mg/mL (~52.08 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (1.30 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 12.5 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: ≥ 1.25 mg/mL (1.30 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 12.5 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: ≥ 1.25 mg/mL (1.30 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0416 mL | 5.2079 mL | 10.4158 mL | |
| 5 mM | 0.2083 mL | 1.0416 mL | 2.0832 mL | |
| 10 mM | 0.1042 mL | 0.5208 mL | 1.0416 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.
 Effects of YM-254890 (a) and MRS2179 (b) on ADP-induced human platelet intracellular Ca2+elevation.Br J Pharmacol. 2006 May; 148(1): 61–69. |
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 Effects of YM-254890 and MRS2179 on P-selectin expression and fibrinogen binding.Br J Pharmacol. 2006 May; 148(1): 61–69. |
 Effect of YM-254890 on human platelet shape change after the addition of various agonists.
Effect of YM-254890 on SIPA in human PRP.Br J Pharmacol. 2006 May; 148(1): 61–69. |
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