53714-56-0 Usage
Description
Leuprorelin, also known as Leuprolide, is a synthetic water-soluble nonapeptide analogue of gonadotropin-releasing hormone (GnRH). It is produced by the hypothalamus and has both ends closed. Leuprorelin stimulates the pituitary gland to secrete gonadotropins, which in turn induce the production of steroids in the reproductive organs. It is a highly active luteinizing hormone-releasing hormone (LHRH) agonist and is used to regulate the secretion of gonadal hormones, increasing the serum levels of testosterone and dihydrotestosterone. Leuprorelin is hygroscopic, appearing as a white or almost white powder.
Uses
Used in Reproductive System Disease Treatment:
Leuprorelin is used as a therapeutic agent for treating various reproductive system diseases, including prostate cancer, uterine fibroids, ovarian cysts, breast cancer, and cryptorchidism in children. It functions by promoting the release of luteinizing hormone (LHRH) and follicle-stimulating hormone (FSH) from the anterior pituitary, thereby regulating gonadal hormone secretion and increasing serum testosterone and dihydrotestosterone levels.
Used in Prostate Cancer Treatment:
Leuprorelin is used as a highly active LHRH agonist for the treatment of prostate cancer. It helps in suppressing gonadal sex hormone production, which is crucial for the growth and progression of prostate cancer cells.
Used in Central Precocious Puberty Treatment:
Leuprorelin is used as a subcutaneous hydrogel implant, particularly as the acetate salt, for the treatment of central precocious puberty in children. It helps in suppressing the early onset of puberty by regulating the secretion of gonadal hormones.
Used in Pharmaceutical Industry:
Leuprorelin is used as a highly active gonadotropin-releasing hormone (gonadorelin) analogue in the pharmaceutical industry. Its synthetic nature allows for controlled production and consistent quality, making it a valuable asset in the development of medications for various reproductive system diseases and conditions.
Mechanism of action
Leuprorelin is a nonapeptide synthetic analogue of Luteinizing Hormone Releasing Hormone (LHRH), which can promote the release of follicle stimulating hormone from the anterior pituitary, thereby reducing the increased testosterone concentration to castrate levels. When the administration is stopped, gonadotropins and androgens can return to normal concentrations.
Pharmacokinetics
Leuprolide acetate(Leuprorelin) is ineffective orally. Good absorption by subcutaneous or intramuscular injection. A single subcutaneous injection of 3.75mg, the blood concentration of 1 to 2 days peaked at 1 to 2ng/ml. For prostate cancer, 3.75mg is injected subcutaneously each time, once every 4 lookchem weeks, for a total of 3 injections, reaching a steady-state blood concentration of 0.1-1ng/ml. This product is hydrolyzed into 4 degradation products in the body and excreted by the kidneys. The urinary excretion rates of the original drug and metabolites were 2.9% and 1.5% after a single subcutaneous injection 28 days.
Adverse reactions
The main side effects of Leuprorelin are fever, heat sensation and elevated AST, ALT, γ-GTP and AKP. Sometimes there are facial flushing, sweating, loss of libido, impotence, feminized breasts, testicular atrophy, perineal discomfort and other endocrine system phenomena; abnormal electrocardiogram and increased ratio of heart and chest, bone pain, shoulder, lower back, limb pain, Urinary retention, frequent urination, hematuria, nausea, vomiting, loss of appetite, rash, itching and other allergic reactions and pain, induration, and redness at the injection site. Rarely, edema, chest pressure, chills, tiredness, weight gain, abnormal perception, tinnitus, hearing loss, TG, uric acid and BUN are increased.
Originator
Eligard,Atrix Laboratories, Inc.
Indications
Leuprolide is a potent LH-RH agonist for the first
several days to a few weeks after initiation of therapy,
and therefore, it initially stimulates testicular and ovarian
steroidogenesis. Because of this initial stimulation of
testosterone production, it is recommended that patients
with prostatic cancer be treated concurrently with
leuprolide and the antiandrogen flutamide (discussed
earlier). Leuprolide is generally well tolerated, with hot
flashes being the most common side effect.
Therapeutic Function
Antineoplastic
Synthesis
The synthesis process of Leuprorelin includes the following steps:(1) Fmoc-Pro-HMPB-AM resin is obtained from Fmoc-Pro-OH and HMPB-AM resin with a substitution degree of 0.2mmol/g~1.2mmol/g as starting materials;(2) The Fmoc-Pro-HMPB-AM resin was coupled one by one by Fmoc/tBu solid phase method to connect amino acids with protective groups in sequence, and the side chain fully protected leuprolide precursor peptide-HMPB-AM was synthesized Resin;(3) Cut the side chain fully protected leuprolide precursor peptide-HMPB-AM resin to obtain the side chain fully protected leuprolide precursor peptide;(4) Fully protected side chain leuprolide precursor peptide undergoes ethylamination to obtain side chain fully protected leuprolide;(5) Leuprolide is fully protected on the side chain by removing the side chain protecting group to obtain the crude leuprolide peptide;(6) The crude leuprorelin peptide is separated and purified by a high-pressure liquid phase column and lyophilized to obtain the leuprolide refined peptide.
Check Digit Verification of cas no
The CAS Registry Mumber 53714-56-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,3,7,1 and 4 respectively; the second part has 2 digits, 5 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 53714-56:
(7*5)+(6*3)+(5*7)+(4*1)+(3*4)+(2*5)+(1*6)=120
120 % 10 = 0
So 53714-56-0 is a valid CAS Registry Number.
InChI:InChI=1/C59H84N16O12/c1-6-63-57(86)48-14-10-22-75(48)58(87)41(13-9-21-64-59(60)61)68-51(80)42(23-32(2)3)69-52(81)43(24-33(4)5)70-53(82)44(25-34-15-17-37(77)18-16-34)71-56(85)47(30-76)74-54(83)45(26-35-28-65-39-12-8-7-11-38(35)39)72-55(84)46(27-36-29-62-31-66-36)73-50(79)40-19-20-49(78)67-40/h7-8,11-12,15-18,28-29,31-33,40-48,65,76-77H,6,9-10,13-14,19-27,30H2,1-5H3,(H,62,66)(H,63,86)(H,67,78)(H,68,80)(H,69,81)(H,70,82)(H,71,85)(H,72,84)(H,73,79)(H,74,83)(H4,60,61,64)/t40-,41-,42-,43+,44-,45-,46-,47-,48-/m0/s1
53714-56-0Relevant articles and documents
Synthesis, Stability and Direct Antiproliferative Effect of New Cysteine Modified GnRH Analogs
Li, Songtao,Zhao, Hongling,Wang, Ruxing,Wang, Jianping,Mao, Xiaoxia,Hao, Ting,Chang, Xiaomin,Zhao, Enhong,Yin, Zhifeng,Deng, Shuhua,Yang, Yaqi,Wang, Huina
, p. 1361 - 1367 (2019)
It is demonstrated that gonadotropin-releasing hormone (GnRH) analogs can directly inhibit the proliferation of reproductive tissue cancer cells, but the poor pharmacokinetic properties still restrict their application in treating hormone-dependent diseases. Modifications in position 6 and 10 of natural GnRH can improve the metabolic stability. In order to study the effect of incorporation Cys6 substitution with C-terminal Pro9-NHEt modification and dimerization of linear peptides on metabolic stability and antiproliferative activity of GnRH analogs, two new GnRH analogs [l-Cys6, desGly10, Pro9-NHEt]-GnRH (1) and [d-Cys6, desGly10, Pro9-NHEt]-GnRH (2), and their corresponding dimer derivatives ([l-Cys6, desGly10, Pro9-NHEt]-GnRH)2 (3) and ([d-Cys6, desGly10, Pro9-NHEt]-GnRH)2 (4) were synthesized. Incubation of these analogs with human serum was carried out to evaluate their metabolic stability, and direct growth inhibitory effect of the two dimer derivatives 3 and 4 on MCF-7 human breast cancer cell line was examined by MTT assay. The metabolic stability of dimer derivatives 3 and 4 was remarkably improved in comparison with natural GnRH. The d-Cys6 substituted dimer derivative 4 exhibited higher inhibitory effect (29.6–39.7% growth reduction) on cell growth than its corresponding counterpart 3 (21.8–26.2% growth reduction) at concentration range of 50, 100 and 200 μΜ. The cell growth inhibition of leuprolide was 16.4–27.2% at the tested concentrations. The dimer derivative 4 was the most stable and active GnRH analog in this study and has the potential for future preclinical investigations as promising antitumor drug candidate.
A catalytic one-step synthesis of peptide thioacids: the synthesis of leuprorelin via iterative peptide-fragment coupling reactions
Matsumoto, Takuya,Sasamoto, Koki,Hirano, Ryo,Oisaki, Kounosuke,Kanai, Motomu
supporting information, p. 12222 - 12225 (2018/12/01)
A catalytic one-step synthesis of peptide thioacids was developed. The oxygen-sulfur atom exchange reaction converted the carboxy group at the C-terminus of the peptides into a thiocarboxy group with suppressed epimerization. This method was successfully applied to the synthesis of the peptide drug leuprorelin via an iterative fragment-coupling protocol.
Solution-phase synthesis of leuprolide
-
, (2008/06/13)
The present application concerns a solution-phase method for the synthesis of leuprolin. Leuprolin is a nonapeptide having strong ovulation-inducing activity, and has the following formula: 5-oxo-L-prolyl- L-histidyl- L-tryptophyl- L-seryl- L-tyrosyl -D-leucyl -L-leucyl- L-arginyl- N-ethyl-L-prolinamide.