Absorption, Distribution and Excretion
Buserelin is water soluble and readily absorbed after subcutaneous injection (70% bioavailable). However, bioavailability after oral absorption. When administered correctly via the nasal route, it may be absorbed in the nasal mucosa to achieve sufficient plasma levels.
Buserelin and its inactive metabolites are excreted via the renal and biliary routes. In man it is excreted in urine at 50% in its intact form.
Buserelin circulates in serum predominantly in intact active form. Preferred accumulation is preferentially in the liver and kidneys as well as in the anterior pituitary lobe, the biological target organ.

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Metabolism / Metabolites
It is metabolized and subsequently inactivated by peptidase (pyroglutamyl peptidase and chymotrypsin-like endopeptidase) in the liver and kidneys as well as in the gastrointestinal tract. In the pituitary gland, it is inactivated by membrane-located enzymes.

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Biological Half-Life
The elimination half-life is approximately 50 to 80 minutes following intravenous administration, 80 minutes after subcutaneous administration and approximately 1 to 2 hours after intranasal administration.

Protein Binding
15%

Buserelin is an oligopeptide.
Buserelin is a synthetic peptide analog of the luteinizing hormone-releasing hormone (LHRH) agonist, which stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). It is used in prostate cancer treatment.
Buserelin is a synthetic analog of gonadotropin-releasing hormone (GnRH). Buserelin binds to and activates pituitary gonadotropin releasing hormone (GnRH) receptors. Prolonged administration of buserelin results in sustained inhibition of gonadotropin production, suppression of testicular and ovarian steroidogenesis, and reduced levels of circulating gonadotropin and gonadal steroids. Buserelin is more potent that GnRH. (NCI04)
A potent synthetic analog of GONADOTROPIN-RELEASING HORMONE with D-serine substitution at residue 6, glycine10 deletion, and other modifications.
See also: Buserelin Acetate (has salt form).

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Drug Indication
Buserelin may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), and in assisted reproduction.

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Mechanism of Action
Buserelin stimulates the pituitary gland's gonadotrophin-releasing hormone receptor (GnRHR). Buserelin desensitizes the GnRH receptor, reducing the amount of gonadotropin. In males, this results in a reduction in the synthesis and release of testosterone. In females, estrogen secretion is inhibited. While initially, there is a rise in FSH and LH levels, chronic administration of Buserelin results in a sustained suppression of these hormones.

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Pharmacodynamics
The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LHRH effect. The effects of buserelin on FSH and LH release are 20 to 170 times greater than those of LHRH. Buserelin also has a longer duration of action than natural LHRH. Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours. Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50-500 mcg SC/day or 300-1200 mcg IN/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland as well as in patients with endometriosis.

C60H86N16O13

1239.43

1238.656

57982-77-1

68630-75-1 (acetate salt)

50225

Typically exists as solid at room temperature

1.4±0.1 g/cm3

1.671

0.7

15

15

33

89

2450

9

CCNC([C@@H]1CCCN1C([C@@H](NC([C@@H](NC([C@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H](NC([C@@H]2CCC(N2)=O)=O)CC3=CN=CN3)=O)CC4=CNC5=CC=CC=C45)=O)CO)=O)CC6=CC=C(O)C=C6)=O)COC(C)(C)C)=O)CC(C)C)=O)CCCNC(N)=N)=O)=O

CUWODFFVMXJOKD-UVLQAERKSA-N

InChI=1S/C60H86N16O13/c1-7-64-57(87)48-15-11-23-76(48)58(88)41(14-10-22-65-59(61)62)69-51(81)42(24-33(2)3)70-56(86)47(31-89-60(4,5)6)75-52(82)43(25-34-16-18-37(78)19-17-34)71-55(85)46(30-77)74-53(83)44(26-35-28-66-39-13-9-8-12-38(35)39)72-54(84)45(27-36-29-63-32-67-36)73-50(80)40-20-21-49(79)68-40/h8-9,12-13,16-19,28-29,32-33,40-48,66,77-78H,7,10-11,14-15,20-27,30-31H2,1-6H3,(H,63,67)(H,64,87)(H,68,79)(H,69,81)(H,70,86)(H,71,85)(H,72,84)(H,73,80)(H,74,83)(H,75,82)(H4,61,62,65)/t40-,41-,42-,43-,44-,45-,46-,47+,48-/m0/s1

(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-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.)