Leuprorelin acetate
Synonym(s):des-Gly10-[D -Leu6]-LH-RH ethylamide;Leuprolide acetate salt;Leuprorelin
- CAS NO.:74381-53-6
- Empirical Formula: C61H88N16O14
- Molecular Weight: 1269.47
- MDL number: MFCD00072080
- EINECS: 686-285-8
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-07-10 15:15:42
What is Leuprorelin acetate?
Description
Leuprolide acetate is a potent analog of LH-RH useful in achieving a medical castration in the treatment of advanced prostate cancer. It has also been investigated for the treatment of advanced breast cancer.
Chemical properties
Fluffy Solid
Originator
Takeda (Japan)
The Uses of Leuprorelin acetate
Synthetic nonapeptide agonist analog of LH-RH. Antineoplastic (hormonal).
The Uses of Leuprorelin acetate
Leuprolide acetate USP (Leupron) is used to treat Prostatic carcinoma.
The Uses of Leuprorelin acetate
In mice, leuprolide acetate salt has been used to check the need of estrogen receptor α in spermatogenic cells, for development or function in fertilization.
What are the applications of Application
Leuprolide Acetate is a synthetic gonadotropin inhibitor
Definition
ChEBI: An acetate salt obtained by combining the nonapeptide leuprolide with acetic acid. A long lasting GnRH analog, LH-Rh agonist. It is a synthetic nonapeptide analogue of gonadotropin-releasing hormone, and is used as a subcutaneous hydrogel implant for the t eatment of prostate cancer and for the suppression of gonadal sex hormone production in children with central precocious puberty.
Manufacturing Process
5-Oxo-L-prolyl-L-histidyl-L-tryptophanyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-Larginyl-L-prolylethylamideacetate was prepared by using of Boc strategy on a 2%-crosslinking chloromethylated divinylbenzene-styrene copolymer in a the Merrifield automatic sintesizer apparatus. 4.6 g of this resin/aminoacid material is used for the synthesis of the desired nonapeptide. Each N-blocked aminoacid is added in a three-fold access and allowed to couple to them, existing aminoacid-resin ester in the usual coupling cycle. Ordinarily the solvent used for the coupling reaction is dichloromethane or, when the solubility of the blocked aminoacid is low, a mixture of dichloromethane and DMF. Coupling is effected by the addition of a solution of dicyclohexylcarbodiimide in dichloromethane at a 2.9 fold excess. The sequence used for deprotection, neutralization and coupling of the next aminoacid is done in a fully automatic system. In this manner, the peptide is assembled using in turn Boc-Arg(Tos), Boc-Leu, Boc-D-Leu, Boc-Tyr(Cl2Bzl), Boc-Ser(Bzl), Boc-Trp, Boc-His(DNP), and pGlu wherein all aminoacids are in the L-form except in the leucine so designated. A 250 mg sample of the above is placed in a hydrogen fluoride reaction with 250 mg vessel of anisole and about 5 ml of anhydrous hydrogen fluoride is distilled into it. After 1 hour at 0°C, the hydrogen fluoride is removed with a stream of dry nitrogen and the residue is taken up in 1% acetic acid. This solution is extracted with ether, and the aqueous phase applied to a 1 time 30 cm column of a highly basic ion exchange resin (marketed by Bio-Rad as AGl resin) in the acetate form. The product is eluted with 0.1 N acetic acid and localized using thin-layer chromatography (CHCl3/MeOH/32% HOAc: 120/90/40, silica gel G, Cl2/tolidine). The product bearing solution is lyophilized, rechromatographed on a Sephadex G-25 (marketed by Pharmacia of Uppsala, Sweden) column. The product eluted is collected and lyophilized to yield a fluffy white solid. An aminoacid analysis shows the expected ratio of all desired aminoacids assembled in the above fashion.
brand name
Eligard (QLT); Lupron(TAP); Viadur (ALZA);CARCINIL.
Therapeutic Function
Antineoplastic
Biochem/physiol Actions
Glp-His-Trp-Ser-Tyr-Leu-Leu-Arg-Pro-NHEt (des-Gly10-[D-Leu6]-LH-RH) is a GnRH (gonadotropin-releasing hormone) agonist, leuprolide. GnRH (Glp-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2), which is also referred as LHRH (luteinizing hormone-releasing hormone) or gonadorelin, is crucial for mammalian reproduction and is released from hypothalamic neurons. It is responsible for the secretion of gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), from the pituitary glands. Mutations in GnRH are associated with normosmic congenital hypogonadotropic hypogonadism. Low concentration of leuprolide can be used for the treatment of endometriosis, uterine fibroids, central precocious puberty and advanced prostate cancer.
Pharmacology
Leuprolide, 5-oxo-L-prolyl-L-histadyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucil-L-leucil-L-arginyl-N-ethyl-L-prolinamide (30.5.9), is made synthetically.
pyroGlu-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt
The nonapeptide leuprolide is a synthetic analog of the decapeptide, gonadotropin releasing hormone, and it exceeds the activity of the natural hormone and significantly elevates
the level of testosterone and dihydrotestosterone in men, and estrogen in women. It also
inhibits follicle-stimulating hormone and leutenizing hormone.
Leuprolide is used for prostate cancer, when orchiectomy or estrogen therapy is counterproductive to the patient. A synonym of this drug is lupron.
Clinical Use
Leuprolide acetate, a synthetic nonapeptide analogue of GnRH that possesses greater potency
than the natural hormone, is a superagonist that is commercially available. Note that leuprolide
acetate contains substitutions that hinder enzymatic degradation, D-Leu and NH-Et in place of
Gly6 and Gly10-NH2, respectively. Leuprolide acetate is reportedly 15-fold the
potency of natural GnRH. When given continuously and in therapeutic doses, leuprolide acetate
inhibits LH and FSH secretion by desensitizing/downregulating the GnRH receptors. After an initial stimulation, chronic administration of leuprolide acetate results
in suppression of ovarian and testicular steroidogenesis. In premenopausal females, estrogens
are reduced to postmenopausal levels; in males, testosterone is reduced to castrate levels.
Leuprolide acetate is administered by daily injections or as depot injections every month, every
3 months, every 4 months, or every 6 months as a palliative treatment in advanced prostatic
carcinoma (as an alternative to orchiectomy). An implant version (Viadur) also is available for
long-term palliative therapy; after implantation of the device into the upper arm, leuprolide
acetate is continuously released over a 12-month period. Because dihydrotestosterone, a
metabolite of testosterone, is able to stimulate the growth of prostate cancer, the ability of
leuprolide acetate to bring testosterone to near castrate levels is why this drug finds use as a
palliative in the advanced disease. The addition of a nonpeptidyl antiandrogen, such as
flutamide or bicalutamide, to the leuprolide acetate regimen inhibits adrenal and testicular
synthesized androgens from binding to or being taken up by target prostate cancer tissue. This
combination therapy helps to control the initial flare-up, by blocking all sources of androgen,
and is referred to as maximal androgen blockade.
Leuprolide acetate, in monthly and every-3-months depot formulations, is useful in treating
women diagnosed with endometriosis, but not for longer than six months because of the chance
of developing osteoporosis.
Central precocious puberty that is idiopathic, or gonadotropin dependent, can cause the
development of secondary sexual characteristics in girls before the age of 8 years and in boys
before the age of 9 years. In addition to the psychological and physiological changes that occur
because of entering puberty too early, there is the risk of the child failing to reach his or her full
adult height. Therefore, leuprolide acetate's ability to suppress LH and sex steroid levels
(testosterone and estradiol) to prepubertal levels is the reason that leuprolide acetate is
approved for use in treating children with this disease. Use of this drug in a child with
precocious puberty will slow or stop that child's secondary sexual development, slow linear
growth and skeletal maturation, and in girls, will bring about the cessation of menstruation.
Drug interactions
Leuprorelin acetate can not take with mang drugs, such as chasteberry, cisapride, dronedarone, pimozide, or thioridazine. This medicine may also interact with the following medications: herbal or dietary supplements, like black cohosh or DHEA; female hormones, like estrogens or progestins and birth control pills, patches, rings, or injections; male hormones, like testosterone; other medicines that prolong the QT interval (abnormal heart rhythm).
Side Effects
Side effects: allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue; breathing problems; chest pain; depression or memory disorders; pain in your legs or groin; pain at site where injected or implanted; seizures; severe headache; signs and symptoms of high blood sugar such as being more thirsty or hungry or having to urinate more than normal. You may also feel very tired or have blurry vision; swelling of the feet and legs; suicidal thoughts or other mood changes; visual changes; vomiting
Properties of Leuprorelin acetate
Melting point: | 150-155°C |
storage temp. | -20°C |
solubility | DMSO (Slightly), Methanol (Slightly) |
form | Solid |
color | White to Off-White |
Merck | 14,5457 |
Safety information for Leuprorelin acetate
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H315:Skin corrosion/irritation |
Precautionary Statement Codes |
P264:Wash hands thoroughly after handling. P264:Wash skin thouroughly after handling. P280:Wear protective gloves/protective clothing/eye protection/face protection. P302+P352:IF ON SKIN: wash with plenty of soap and water. P332+P313:IF SKIN irritation occurs: Get medical advice/attention. |
Computed Descriptors for Leuprorelin acetate
InChIKey | RGLRXNKKBLIBQS-XNHQSDQCSA-N |
Abamectin manufacturer
Piramal Pharma Solutions
BDR Pharmaceuticals International Pvt Ltd
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