| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg | |||
| Other Sizes |
| Targets |
Gonadotropin-releasing hormone receptor (GNRHR). Acts as a potent agonist with high affinity binding (Ki in the low nanomolar range). Continuous exposure leads to receptor downregulation and desensitization, suppressing LH and FSH secretion.
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| ln Vitro |
The hypothalamic-neurohypophyseal system releases oxytocin (VP) in vivo when histrelin (10–100 nM) acetate is administered [4]. (Ad Extra Minute)[5].
In vitro, histrelin binds to the GnRH receptor with high affinity (Ki approximately 0.2 nM in CHO cells expressing the human receptor) and stimulates the release of LH and FSH from pituitary cells in culture with EC50 in the low nanomolar range. It is a standard agonist in GnRH receptor functional assays and is used as a reference compound for studying GnRH receptor pharmacology. |
| ln Vivo |
In Csfmop/Csfmop mice, histrelin (0.1 mg/kg, subcutaneous injection) acetate raises circulatory LH concentrations [2]. Histrelin (10, 30, or 100 μg/day, subcutaneous injection) acetate stabilizes stromal depletion and decreases the number of intraretinal glands [3].
In vivo, histrelin acetate initially stimulates LH and FSH release, increasing serum testosterone levels (in males) or estradiol levels (in females). With continued administration (e.g., via subcutaneous hydrogel implant), it desensitizes the pituitary, leading to a sustained suppression of sex hormone production. In males, testosterone is reduced to castration levels (<50 ng/dL) within 2 to 4 weeks of treatment initiation. This is used therapeutically in prostate cancer and precocious puberty. |
| Enzyme Assay |
GnRH receptor binding assay: Membranes from cells expressing GnRH receptor (e.g., CHO-GnRHR transfectants or pituitary membrane preparations) are incubated with a radiolabeled GnRH agonist (e.g., [¹2⁵I]buserelin or [3H]histrelin, 0.05-0.2 nM) and varying concentrations of unlabeled histrelin (0.001-10,000 nM) in binding buffer (50 mM Tris-HCl pH 7.4, 5 mM MgCl2, 0.1% BSA) for 2 hours at 4degC. Bound radioactivity is separated by filtration through GF/C filters and quantified. Ki is calculated using the Cheng-Prusoff equation.
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| Cell Assay |
LH/FSH release assay: Primary rat pituitary cells or gonadotrope cell lines (e.g., LbetaT2 cells) are seeded in 24-well plates and treated with histrelin (0.001-1000 nM) for 2-4 hours. Supernatants are collected and LH and FSH levels are measured by ELISA or RIA. EC50 for hormone release is determined from dose-response curves.
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| Animal Protocol |
Animal models of hormone-dependent diseases: Histrelin is administered to rodents (subcutaneous implant, osmotic minipump, or daily injection) and its effects on serum LH, FSH, and testosterone levels are measured over time. Models of prostate cancer (e.g., castration-sensitive or castration-resistant xenografts) or precocious puberty are used to assess efficacy in suppressing sex hormone-dependent tumor growth or puberty onset.
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| ADME/Pharmacokinetics |
Following subcutaneous insertion of one Vantas® implant (50 mg histrelin acetate) in prostate cancer patients, peak serum concentrations of 1.10 +/- 0.375 ng/mL occurred at a median of 12 hours. Continuous subcutaneous release is evident, with serum levels sustained throughout the 52-week dosing period; mean serum concentration at week 52 is 0.13 +/- 0.065 ng/mL. The average rate of drug release is 56.7 +/- 7.71 mcg/day over 52 weeks. Relative bioavailability is 92% compared to subcutaneous bolus. Mean half-life is approximately 4 hours, apparent clearance is 179 mL/min, and apparent volume of distribution is 58 L. Histrelin is not active when given orally.
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| Toxicity/Toxicokinetics |
Common adverse effects include those related to sex hormone suppression (androgen deprivation), such as hot flashes, decreased libido, erectile dysfunction, osteoporosis, and fatigue. Initial flare phenomenon (transient increase in testosterone) may exacerbate symptoms in prostate cancer patients. Injection site reactions (pain, erythema, infection) may occur with implant placement. Animal and human studies indicate that chronic administration is associated with an increase in tumors of hormonally responsive tissues. QTc prolongation of about 6 msec has been observed.
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| References | |
| Additional Infomation |
Histrelin Acetate acetate may cause developmental toxicity, depending on state or federal labeling requirements. Histrelin Acetate acetate is the acetate form of Histrelin Acetate, a long-acting synthetic gonadotropin-releasing hormone (GnRH) nonapeptide analog with potential antitumor activity. After administration, Histrelin Acetate binds to and activates GnRH receptors; long-term administration leads to pituitary GnRH receptor desensitization and inhibits the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), resulting in a significant decrease in testosterone production in men and potentially inhibiting the progression of androgen receptor-positive tumors; in women, long-term administration leads to reduced estradiol production. See also: Histrelin Acetate acetate (note moved to).
Histrelin acetate is an FDA-approved drug: Vantas® implant (50 mg) for palliative treatment of advanced prostate cancer (approved 2004) and Supprelin® LA implant (50 mg) for central precocious puberty (approved 2007). It is a synthetic nonapeptide GnRH agonist. The implant consists of a non-biodegradable polymeric matrix that allows diffusion-controlled, sustained release of histrelin at ~50-60 ug/day over 12 months. |
| Molecular Formula |
C66H86N18O12.NC2H4O2
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|---|---|
| Molecular Weight |
1383.55
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| Exact Mass |
1442.71
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| CAS # |
220810-26-4
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| Related CAS # |
Histrelin;76712-82-8
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| PubChem CID |
25084151
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| Appearance |
White to off-white solid powder
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| LogP |
3.979
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| Hydrogen Bond Donor Count |
16
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| Hydrogen Bond Acceptor Count |
17
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| Rotatable Bond Count |
34
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| Heavy Atom Count |
100
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| Complexity |
2690
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| Defined Atom Stereocenter Count |
9
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| SMILES |
CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(C=N2)CC3=CC=CC=C3)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CC7=CN=CN7)NC(=O)[C@@H]8CCC(=O)N8.CC(=O)O
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| InChi Key |
OWAUGAMNPZHEOJ-YKZVIGSYSA-N
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| InChi Code |
InChI=1S/C66H86N18O12.C2H4O2/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47;1-2(3)4/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71);1H3,(H,3,4)/t47-,48-,49-,50-,51-,52-,53+,54-,55-;/m0./s1
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| Chemical Name |
acetic acid;(2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-3-(1-benzylimidazol-4-yl)-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]-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
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL
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|---|---|
| Solubility (In Vivo) |
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.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] Oral Formulations
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). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.7228 mL | 3.6139 mL | 7.2278 mL | |
| 5 mM | 0.1446 mL | 0.7228 mL | 1.4456 mL | |
| 10 mM | 0.0723 mL | 0.3614 mL | 0.7228 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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