53714-56-0 Usage
Description
Leuprorelin(Leuprolide?) is a synthetic water-soluble nonapeptide with both ends closed, and also a highly active analogue of luteinizing hormone releasing hormone (LHRH or GnRH) produced by the hypothalamus. It can stimulate the pituitary gland to secrete gonadotropins and induce the production of steroids in the reproductive organs.
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.
Uses
Different sources of media describe the Uses of 53714-56-0 differently. You can refer to the following data:
1. Leuprorelin is a nonapeptide synthetic analogue of gonadotropin (GnRH), which can promote the release of luteinizing hormone (LHRH) and follicle stimulating hormone (FSH) from the anterior pituitary, regulate the secretion of gonadal hormones, and increase the serum levels of testosterone and dihydrotestosterone. Concentration, so as to achieve the function of treating reproductive system diseases. It is used to treat prostate cancer, uterine fibroids, ovarian cysts, breast cancer and cryptorchidism in children.
2. Highly active luteinizing hormone releasing hormone (LHRH) agonist
3. Gonadotropin releasing hormone (gonadorelin) analogue; treatment of prostate cancer.
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.
Chemical Properties
Hygroscopic, white or almost white powder.
Originator
Eligard,Atrix Laboratories, Inc.
Definition
ChEBI: An oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, D-leucyl, leucyl, arginyl, and N-ethylprolinamide residues joined in sequence. Leuprorelin is a synthetic nonapeptide analogue of gonadotropin-releasi
g hormone, and is used as a subcutaneous hydrogel implant (particularly as the acetate salt) for the treatment of prostate cancer and for the suppression of gonadal sex hormone production in children with central precocious puberty.
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 Vinylogous Photocleavage Strategy Allows Direct Photocaging of Backbone Amide Structure
Mangubat-Medina, Alicia E.,Martin, Samuel C.,Hanaya, Kengo,Ball, Zachary T.
supporting information, p. 8401 - 8404 (2018/06/29)
Side-chain modifications that respond to external stimuli provide a convenient approach to control macromolecular structure and function. Responsive modification of backbone amide structure represents a direct and powerful alternative to impact folding and function. Here, we describe a new photocaging method using histidine-directed backbone modification to selectively modify peptides and proteins at the amide N-H bond. A new vinylogous photocleavage method allows photorelease of the backbone modification and, with it, restoration of function.
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.
