Acyline is a novel GnRH antagonist found in animal studies to be a potent suppressor of circulating gonadotropin and testosterone (T) levels. Acyline inhibits basal and GnRH-stimulated serum testosterone concentrations in male dogs. Acyline prevented ovulation, but did not affect ovarian follicular development or gestational corpora lutea in the domestic cat. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men.
Physicochemical Properties
| Molecular Formula | C80H102CLN15O14 |
| Molecular Weight | 1533.21 |
| Exact Mass | 1531.741 |
| CAS # | 170157-13-8 |
| Related CAS # | Acyline TFA |
| PubChem CID | 16137348 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.3±0.1 g/cm3 |
| Boiling Point | 1774.1±65.0 °C at 760 mmHg |
| Flash Point | 1026.7±34.3 °C |
| Vapour Pressure | 0.0±0.3 mmHg at 25°C |
| Index of Refraction | 1.611 |
| LogP | 5.71 |
| Hydrogen Bond Donor Count | 14 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 40 |
| Heavy Atom Count | 110 |
| Complexity | 3050 |
| Defined Atom Stereocenter Count | 10 |
| SMILES | C(N)(=O)[C@@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCNC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC1=CC=C(NC(C)=O)C=C1)NC(=O)[C@H](CC1=CC=C(NC(C)=O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC1=CC=CN=C1)NC(=O)[C@@H](CC1=CC=C(Cl)C=C1)NC(=O)[C@@H](CC1=CC=C2C(=C1)C=CC=C2)NC(C)=O |
| InChi Key | ZWNUQDJANZGVFO-YHSALVGYSA-N |
| InChi Code | InChI=1S/C80H102ClN15O14/c1-46(2)37-63(72(102)89-62(18-11-12-35-84-47(3)4)80(110)96-36-14-19-70(96)79(109)85-48(5)71(82)101)90-74(104)66(40-53-23-30-60(31-24-53)86-49(6)98)92-76(106)67(41-54-25-32-61(33-26-54)87-50(7)99)94-78(108)69(45-97)95-77(107)68(43-56-15-13-34-83-44-56)93-75(105)65(39-52-21-28-59(81)29-22-52)91-73(103)64(88-51(8)100)42-55-20-27-57-16-9-10-17-58(57)38-55/h9-10,13,15-17,20-34,38,44,46-48,62-70,84,97H,11-12,14,18-19,35-37,39-43,45H2,1-8H3,(H2,82,101)(H,85,109)(H,86,98)(H,87,99)(H,88,100)(H,89,102)(H,90,104)(H,91,103)(H,92,106)(H,93,105)(H,94,108)(H,95,107)/t48-,62+,63+,64-,65-,66-,67+,68-,69+,70+/m1/s1 |
| Chemical Name | (S)-N-((R)-1-amino-1-oxopropan-2-yl)-1-((2S,5S,8R,11S,14S,17R,20R,23R)-8,11-bis(4-acetamidobenzyl)-20-(4-chlorobenzyl)-14-(hydroxymethyl)-5-isobutyl-2-(4-(isopropylamino)butyl)-23-(naphthalen-2-ylmethyl)-4,7,10,13,16,19,22,25-octaoxo-17-(pyridin-3-ylmethyl)-3,6,9,12,15,18,21,24-octaazahexacosan-1-oyl)pyrrolidine-2-carboxamide |
| Synonyms | Acyline MER104 MER-104 MER 104. |
| 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 Vivo | In female Kiss1−/− and Gpr54−/− mice, acyline (50 μg, subcutaneously applied twice daily for five days) disrupts vaginal estrus, reduces uterine weight, and lowers LH levels in female Kiss1−/ mice - Small Rat[1]. Acyline (50 μg, once subcutaneously) increased FSH concentration from 2.87 ng/mL pre-acyline and decreased FSH concentration from 1.51 ng/mL pre-acyline in male Kiss1−/− mice. Following acyl treatment, the levels in male Gpr54−/− mice was lowered to 1.95 ng/mL. |
| Animal Protocol |
Animal/Disease Models: Female Kiss1−/− and Gpr54−/− mice [1] Doses: 50 μg (1 mg/mL in PBS) Route of Administration: subcutaneous injection; twice (two times) daily; 5 days Experimental Results: 13 mice received Within 4 days after acyline treatment, 12 Kiss1−/− mice left estrus, whereas only 2 of 17 mice receiving vehicle left estrus. In addition, 7 of 8 Gpr54−/− mice received acyline left estrus, whereas 1 of 7 mice received vehicle. Compared with the vehicle group, the uterine weight of Kiss1−/− and Gpr54−/− mice in the treatment group was diminished, and the serum LH concentration of Kiss1−/− mice was diminished. |
| References |
[1]. Kisspeptin/Gpr54-independent gonadotrophin-releasing hormone activity in Kiss1 and Gpr54 mutant mice. J Neuroendocrinol. 2009 Dec;21(12):1015-23. |
| Additional Infomation | Acyline has been investigated for the prevention and treatment of Hypogonadism and Contraception. |
Solubility Data
| Solubility (In Vitro) | May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *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. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.6522 mL | 3.2611 mL | 6.5223 mL | |
| 5 mM | 0.1304 mL | 0.6522 mL | 1.3045 mL | |
| 10 mM | 0.0652 mL | 0.3261 mL | 0.6522 mL |