Absorption, Distribution and Excretion
Following subcutaneous injection, ganerilipic acid is rapidly absorbed, with a mean absolute bioavailability of approximately 91%. Its time to peak concentration (Tmax) is 1 to 2 hours. Steady-state serum concentrations of ganerilipic acid are reached three days after administration. In healthy female volunteers, following a single intravenous injection of radiolabeled ganerilipic acid, ganerilipic acid remains the dominant compound in plasma (accounting for 50% to 70% of total plasma radioactivity) for up to 4 hours; the dominant compound in urine (accounting for 17.1% to 18.4% of the administered dose) persists for up to 24 hours. Ganerilipic acid is not detected in feces. On average, following a single intravenous injection of 1 mg [¹⁴C]-ganerilipic acid, 97.2% of the total dose of radiolabeled ganerilipic acid is excreted in feces and urine within 288 hours (75.1% and 22.1%, respectively). Urinary excretion was almost complete within 24 hours, while fecal excretion plateaued at 192 hours post-administration. The mean (standard deviation) volume of distribution after a single subcutaneous injection of 250 mcg ganirelix in healthy women was 43.7 (11.4) L. The clearance after a single subcutaneous injection of 250 mcg ganirelix was approximately 2.4 L/h. Metabolites/Metabolites: Metabolites are small peptide fragments formed by enzymatic hydrolysis of ganirelix at specific sites. Ganierilipin 1-4 and 1-6 peptides were the major metabolites observed in feces. Biological Half-Life: The elimination half-life (t½) after a single subcutaneous injection of 250 mcg was approximately 13 hours.

Protein Binding
The binding rate of in vitro proteins to human plasma was 81.9%.

Garneliximab is a polypeptide. Garneliximab is a synthetic decapeptide and a competitive gonadotropin-releasing hormone (GnRH) antagonist. Garneliximab is derived from endogenous GnRH and has amino acid substitutions. Garneliximab is indicated for controlled ovarian hyperstimulation in assisted reproductive technologies. The first successful pregnancy following the use of garneliximab in assisted reproduction was reported in 1998. Garneliximab was first approved by the U.S. Food and Drug Administration (FDA) on July 29, 1999. Garneliximab is a gonadotropin-releasing hormone receptor antagonist. The mechanism of action of garneliximab is as a gonadotropin-releasing hormone receptor antagonist. The physiological effect of garneliximab is through reducing the secretion of gonadotropin-releasing hormone (GnRH). See also: Garneliximab acetate (salt form). Drug Indications Orgalutran is indicated for women undergoing controlled ovarian stimulation (COH) with assisted reproductive technology (ART) to suppress premature luteinizing hormone (LH) surges. It prevents premature LH surges in women undergoing COH with ART. In clinical studies, Orgalutran was used in combination with recombinant human follicle-stimulating hormone (FSH) or continuous follicle-stimulating hormone (COH). It also prevents premature LH surges in women undergoing COH with ART. Mechanism of Action Gonadotropin-releasing hormone (GnRH) is a hypothalamic releasing hormone responsible for promoting the synthesis and release of LH and FSH from the anterior pituitary gland. A significant increase in GnRH release mid-cycle leads to an LH surge, triggering various physiological responses such as ovulation, resumption of meiosis in oocytes, and luteinization. Luteinization leads to elevated serum progesterone levels and decreased estradiol levels. In assisted reproductive technologies (ART), controlled ovarian hyperstimulation (COH) is often combined with other interventions, such as in vitro fertilization (IVF). The advantage of COH is its ability to schedule IVF treatment. In this process, suppressing premature LH surges is crucial, as premature increases in LH levels can hinder the effective maturation of multiple follicles and may lead to abnormally high progesterone levels. Garnirex is designed to suppress premature LH surges by competitively blocking GnRH receptors and their subsequent signaling pathways on pituitary gonadotropin cells. Garnirex's inhibitory effect on gonadotropin secretion is rapid and reversible. Garnirex's inhibitory effect on pituitary LH secretion is more significant than its inhibitory effect on FSH. No initial release of endogenous gonadotropins was detected after using Garnirex, consistent with the antagonist effect.

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Pharmacodynamics
Ganirelix regulates the hypothalamic-pituitary-gonadal axis by rapidly, significantly, and reversibly inhibiting endogenous gonadotropins. During controlled ovarian stimulation, it inhibits the pituitary secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Unlike GnRH agonists, which cause an initial increase in gonadotropin levels, ganirelix does not produce this effect prematurely before suppressing the LH surge. Ganirelix also does not cause the hypoestrogenic side effects, disease exacerbation, and prolonged downregulation phases associated with GnRH agonists. In patients receiving controlled ovarian stimulation, the median duration of ganirelix treatment was 5 days. In one study, after multiple doses of 0.25 mg ganirelix, serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) concentrations decreased by 74%, 32%, and 25%, respectively, from baseline after the last dose. Serum hormone levels returned to pre-treatment levels within two days after the last injection.

C80H113N18O13CL

1570.31902

1568.842

123246-29-7

16130957

Typically exists as solid at room temperature

1.3±0.1 g/cm3

1.632

6.75

16

16

48

112

3030

10

CCN/C(/NCCCC[C@@H](NC(CNC(CNC(CNC(CNC([C@H](NC(C)=O)CC1=CC2=CC=CC=C2C=C1)=O)=O)=O)=O)=O)C(N[C@@H](CC(C)C)C(N[C@@H](CCCCN/C(/NCC)=N/CC)C(N1[C@H](C(N[C@H](C)C(N)=O)=O)CCC1)=O)=O)=O)=N\CC

GJNXBNATEDXMAK-PFLSVRRQSA-N

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

(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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

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

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)