Absorption, Distribution and Excretion
Rapidly absorbed into systemic circulation after intranasal administration. The average bioavailability of a 400 µg dose is 2.8% (range 1.2% to 5.6%). Not absorbed after oral administration. Metabolism/Metabolites Enzymatic hydrolysis. Biological Half-Life 3 hours

Protein Binding
Approximately 80%.

Ludwig C, Desmoulins PO, Driancourt MA, Goericke-Pesch S, Hoffmann B. Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin as a removable implant 'Gonazon'; a preclinical trial. Theriogenology. 2009 Apr 15;71(7):1037-45. doi: 10.1016/j.theriogenology.2008.10.015. Epub 2009 Feb 23. PubMed PMID: 19233456.

Nafarelin acetate may cause developmental toxicity depending on state or federal labeling requirements. Nafarelin is a potent synthetic gonadotropin-releasing hormone agonist with its 6th residue replaced by 3-(2-naphthyl)-D-alanine. Nafarelin has been used to treat central precocious puberty and endometriosis. Nafarelin is a gonadotropin-releasing hormone receptor agonist. Its mechanism of action is as a gonadotropin-releasing hormone receptor agonist. Nafarelin acetate is the acetate form of nafarelin, a modified synthetic porcine luteinizing hormone (LH)-releasing hormone peptide analog with gonadotropin-releasing hormone (GnRH) agonist activity. When inhaled nasally, nafarelin acetate binds to GnRH receptors. This initially leads to the pituitary gland releasing gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH); however, continued stimulation of GnRH receptors leads to receptor desensitization, resulting in reduced FSH and LH secretion. In women, suppression of gonadotropin secretion leads to hypogonadotropic hypogonadism, which in turn results in reduced estrogen and progesterone production and anovulation. In men, suppression of LH secretion prevents the interstitial cells of the testes from producing and releasing testosterone, leading to a significant decrease in testosterone production, approaching castration levels. Nafarelin is a potent anabolic gonadotropin-releasing hormone (GnRH) agonist with its 6th residue replaced by 3-(2-naphthyl)-D-alanine. Nafarelin has been used to treat central precocious puberty and endometriosis. See also: Nafarelin acetate (salt form). Drug Indications Nafarelin is indicated for the treatment of central precocious puberty (true precocious puberty, GnRH-dependent precocious puberty, and complete same-sex precocious puberty) in boys and girls, as well as endometriosis. FDA Label Mechanism of Action Similar to GnRH, initial or intermittent use of nafarelin stimulates the pituitary gland to release gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which transiently increases estradiol production in women and testosterone production in both sexes. However, continuous daily use of nafarelin persistently occupies gonadotropin-releasing hormone (GnRH) receptors, leading to reversible downregulation of GnRH receptors in the pituitary gland and desensitization of pituitary gonadotropin cells. This results in a significant and sustained decrease in LH and FSH production. The reduction in gonadotropin production and release leads to a significant and reversible decrease in the synthesis of estradiol, progesterone, and testosterone in the ovaries or testes. Like normal endometrium, endometriosis lesions also contain estrogen receptors. Estrogen stimulates endometrial growth. Nafarelin induces anovulation and amenorrhea, and lowers serum estradiol levels to postmenopausal levels, thereby inducing atrophy of endometriosis lesions. However, nafarelin does not eliminate the underlying pathophysiological mechanisms of endometriosis. In children with central precocious puberty treated with nafarelin, serum luteinizing hormone (LH), testosterone, and estradiol levels return to pre-pubertal levels. This leads to suppressed development of secondary sexual characteristics, slowed linear growth, and slower skeletal maturation. Upon discontinuation of nafarelin, the drug's effects reverse, meaning that follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels typically return to pre-treatment levels.

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Pharmacodynamics
Nafarelin is a potent agonist analog of gonadotropin-releasing hormone (GnRH).
In the initial stages of administration, nafarelin stimulates the pituitary gland to release gonadotropins, including luteinizing hormone (LH) and follicle-stimulating hormone (FSH), resulting in a temporary increase in gonadal steroid production. Repeated administration eliminates the stimulatory effect on the pituitary gland. Twice-daily administration leads to a decrease in gonadal steroid secretion for approximately 4 weeks; therefore, tissues and functions dependent on gonadal steroids enter a quiescent state. After discontinuation of nafarelin, pituitary and ovarian function return to normal, and serum estradiol levels return to pre-treatment levels. Recurrence of endometriosis is common after discontinuation of any hormone therapy or ovarian- and/or uterus-preserving surgery.

C66H83N17O13

1322.49

1321.635

76932-56-4

86220-42-0 (acetate);76932-56-4;

25077405

Typically exists as solid at room temperature

1.5±0.1 g/cm3

1.711

0.89

16

15

33

96

2730

9

O=C([C@]([H])(C([H])([H])C([H])([H])C([H])([H])/N=C(\N([H])[H])/N([H])[H])N([H])C([C@]([H])(C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H])N([H])C([C@@]([H])(C([H])([H])C1C([H])=C([H])C2=C([H])C([H])=C([H])C([H])=C2C=1[H])N([H])C([C@]([H])(C([H])([H])C1C([H])=C([H])C(=C([H])C=1[H])O[H])N([H])C([C@]([H])(C([H])([H])O[H])N([H])C([C@]([H])(C([H])([H])C1=C([H])N([H])C2=C([H])C([H])=C([H])C([H])=C12)N([H])C([C@]([H])(C([H])([H])C1=C([H])N=C([H])N1[H])N([H])C([C@]1([H])C([H])([H])C([H])([H])C(N1[H])=O)=O)=O)=O)=O)=O)=O)=O)N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(N([H])C([H])([H])C(N([H])[H])=O)=O

(S)-1-(((R)-2-((S)-2-((S)-2-((S)-2-((S)-3-(1H-imidazol-4-yl)-2-((S)-5-oxopyrrolidine-2-carboxamido)propanamido)-3-(1H-indol-3-yl)propanamido)-3-hydroxypropanamido)-3-(4-hydroxyphenyl)propanamido)-3-(naphthalen-2-yl)propanoyl)-L-leucyl-L-arginyl)-N-(2-amino-2-oxoethyl)pyrrolidine-2-carboxamide

RWHUEXWOYVBUCI-ITQXDASVSA-N SMILES

Nafarelin

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.)