Physicochemical Properties
| Molecular Formula | C80H113N18O13CL |
| Molecular Weight | 1570.31902 |
| Exact Mass | 1568.84 |
| CAS # | 124904-93-4 |
| Related CAS # | Ganirelix acetate;129311-55-3 |
| PubChem CID | 16130957 |
| Appearance | Typically exists as solid at room temperature |
| Density | 1.31 g/cm3 |
| LogP | 7.992 |
| Hydrogen Bond Donor Count | 16 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 48 |
| Heavy Atom Count | 112 |
| Complexity | 3030 |
| Defined Atom Stereocenter Count | 10 |
| SMILES | C(NC(C(NC(C(NC(C(NC(C(NC(C(NC(C(NC(C(NC(C(N1CCCC1C(NC(C(N)=O)C)=O)=O)CCCC/N=C(\NCC)/NCC)=O)CC(C)C)=O)CCCC/N=C(\NCC)/NCC)=O)CC1C=CC(O)=CC=1)=O)CO)=O)CC1=CC=CN=C1)=O)CC1C=CC(Cl)=CC=1)=O)CC1C=CC2C(=CC=CC=2)C=1)(=O)C |
| InChi Key | GJNXBNATEDXMAK-PFLSVRRQSA-N |
| InChi Code | InChI=1S/C80H113ClN18O13/c1-9-84-79(85-10-2)88-38-17-15-24-60(70(104)94-62(41-49(5)6)71(105)93-61(25-16-18-39-89-80(86-11-3)87-12-4)78(112)99-40-20-26-68(99)77(111)90-50(7)69(82)103)92-73(107)64(44-53-30-35-59(102)36-31-53)97-76(110)67(48-100)98-75(109)66(46-55-21-19-37-83-47-55)96-74(108)65(43-52-28-33-58(81)34-29-52)95-72(106)63(91-51(8)101)45-54-27-32-56-22-13-14-23-57(56)42-54/h13-14,19,21-23,27-37,42,47,49-50,60-68,100,102H,9-12,15-18,20,24-26,38-41,43-46,48H2,1-8H3,(H2,82,103)(H,90,111)(H,91,101)(H,92,107)(H,93,105)(H,94,104)(H,95,106)(H,96,108)(H,97,110)(H,98,109)(H2,84,85,88)(H2,86,87,89)/t50-,60-,61+,62+,63-,64+,65-,66-,67+,68+/m1/s1 |
| Chemical Name | (2S)-1-[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2S)-2-[[(2S)-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-[bis(ethylamino)methylideneamino]hexanoyl]amino]-4-methylpentanoyl]amino]-6-[bis(ethylamino)methylideneamino]hexanoyl]-N-[(2R)-1-amino-1-oxopropan-2-yl]pyrrolidine-2-carboxamide |
| 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 | Ganirelix (0.1 mg/kg; subcutaneous injection; once daily for 14 days) lowers luteinizing hormone levels in female rats [2]. |
| Animal Protocol |
Animal/Disease Models: Female SD (SD (Sprague-Dawley)) rats, body weight 225–300 mg [2] Doses: 0.1 mg/kg Route of Administration: subcutaneous injection, one time/day for 14 days Experimental Results: diminished luteinizing hormone levels. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Ganirelix is rapidly absorbed following subcutaneous administration with a mean absolute bioavailability of approximately 91%. It has a Tmax ranging from one to two hours. Ganirelix reaches steady-state serum concentrations after three days of administration. Following single-dose intravenous administration of radiolabeled ganirelix to healthy female volunteers, Ganirelix is the major compound present in the plasma (50–70% of total radioactivity in the plasma) up to 4 hours and urine (17.1–18.4% of administered dose) up to 24 hours. Ganirelix is not found in the feces. On average, 97.2% of the total radiolabeled ganirelix dose is recovered in the feces and urine (75.1% and 22.1%, respectively) over 288 h following intravenous single dose administration of 1 mg [14C]-ganirelix. Urinary excretion is virtually complete in 24 h, whereas fecal excretion starts to plateau 192 h after dosing. The mean (SD) volume of distribution of ganirelix in healthy females following subcutaneous administration of a single 250-mcg dose is 43.7 (11.4) L. Clearance following subcutaneous administration of a single 250-mcg dose is approximately 2.4 L/h. Metabolism / Metabolites The metabolites are small peptide fragments formed by enzymatic hydrolysis of ganirelix at restricted sites. The 1–4 peptide and 1–6 peptide of ganirelix are the primary metabolites observed in the feces. Biological Half-Life The elimination half-life (t½) following subcutaneous administration of a single 250-mcg dose is approximately 13 hours. |
| Toxicity/Toxicokinetics |
Protein Binding _In vitro_ protein binding to human plasma is 81.9%. |
| References |
[1]. Ganirelix. Drugs. 2000 Jan;59(1):107-11; discussion 112-3. [2]. Effects of the gonadotropin-releasing hormone antagonist ganirelix on normal micturition and prostaglandin E(2)-induced detrusor overactivity in conscious female rats. Eur Urol. 2011 May;59(5):868-74. |
| Additional Infomation |
Ganirelix is a polypeptide. Ganirelix is a synthetic decapeptide and a competitive gonadotropin-releasing hormone (GnRH) antagonist. Derived from endogenous GnRH, ganirelix has amino acid substitutions. Ganirelix is indicated for controlled ovarian hyperstimulation in assisted reproduction techniques. The first case of pregnancy achieved after the use of ganirelix in an assisted reproduction program was reported in 1998. Ganirelix was first approved by the FDA on July 29, 1999. Ganirelix is a Gonadotropin Releasing Hormone Receptor Antagonist. The mechanism of action of ganirelix is as a Gonadotropin Releasing Hormone Receptor Antagonist. The physiologic effect of ganirelix is by means of Decreased GnRH Secretion. See also: Ganirelix Acetate (has salt form). Drug Indication Ganirelix is indicated for the inhibition of premature luteinizing hormone (LH) surges in women undergoing controlled ovarian hyperstimulation for assisted reproduction techniques (ART). The prevention of premature luteinising-hormone surges in women undergoing controlled ovarian hyperstimulation for assisted reproduction techniques. In clinical studies, Orgalutran was used with recombinant human follicle-stimulating hormone or corifollitropin alfa, the sustained follicle stimulant. Prevention of premature luteinising hormone (LH) surges in women undergoing controlled ovarian hyperstimulation (COH) for assisted reproduction techniques (ART). Mechanism of Action Gonadotropin-releasing hormone (GnRH) is a hypothalamus-derived releasing hormone responsible for the synthesis and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary. At midcycle, a large increase in GnRH release results in an LH surge, which leads to several physiologic actions such as ovulation, resumption of meiosis in the oocyte, and luteinization. Luteinization results in a rise in serum progesterone with an accompanying decrease in estradiol levels. Controlled ovarian hyperstimulation (COH) is performed in conjunction with other interventions like in vitro fertilization (IVF) during assisted reproductive technology (ART). COH is beneficial as it allows the scheduling of IVF treatments. During this intervention, inhibiting premature surges of LH is important because premature elevated LH levels can hinder effective multiple follicular maturation and can lead to an undesirable increase in progesterone levels. Ganirelix aims to suppress premature LH surges by competitively blocking the GnRH receptors on the pituitary gonadotroph and subsequent transduction pathways. Ganirelix-induced suppression of gonadotropin secretion is rapid and reversible. The suppression of pituitary LH secretion by ganirelix is more pronounced than that of FSH. An initial release of endogenous gonadotropins has not been detected with ganirelix, which is consistent with an antagonist effect. |
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 | 0.6368 mL | 3.1841 mL | 6.3681 mL | |
| 5 mM | 0.1274 mL | 0.6368 mL | 1.2736 mL | |
| 10 mM | 0.0637 mL | 0.3184 mL | 0.6368 mL |