YM-254890 (YM254890), a cyclic depsipeptide discovered from Chromobacterium sp. QS3666 culture broth, is a novel, potent and specific Gαq/11 inhibitor with anti-platelet activity. It can inhibit adp-induced platelet aggregation and blocking gαq/11-coupled adp receptor p2y1-mediated ca2+ mobilization. YM-254890 concentration dependently inhibited ADP-induced intracellular Ca2+ elevation, with an IC50 value of 0.92±0.28 μm. YM-254890 had no effect on the binding of fibrinogen to purified GPIIb/IIIa, but strongly inhibited binding to TRAP-stimulated washed platelets.
Physicochemical Properties
| Molecular Formula | C46H69N7O15 |
| Molecular Weight | 960.077973127365 |
| Exact Mass | 959.485 |
| CAS # | 568580-02-9 |
| 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 |
| Appearance | White to off-white solid powder |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 1232.4±65.0 °C at 760 mmHg |
| Flash Point | 699.1±34.3 °C |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.560 |
| LogP | -1.84 |
| Hydrogen Bond Donor Count | 5 |
| Hydrogen Bond Acceptor Count | 15 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 68 |
| Complexity | 1870 |
| Defined Atom Stereocenter Count | 11 |
| 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 |
| InChi Key | QVYLWCAYZGFGNF-WBWCVGBTSA-N |
| 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 |
| 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 |
| Synonyms | YM254890; YM 254890; YM-254890 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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]. |
| References |
[1]. YM-254890, a novel platelet aggregation inhibitor produced by Chromobacterium sp. QS3666. J Antibiot (Tokyo). 2003 Apr;56(4):358-63. [2]. Structure-activity relationship and conformational studies of the natural product cyclic depsipeptides YM-254890 and FR900359. Eur J Med Chem. 2018 Aug 5;156:847-860. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~52.08 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |