Leuprolide Acetate

Leuprolide Acetate is a synthetic nonapeptide-ethylamide analog of native gonadotropin-releasing hormone (GnRH), carrying a D-leucine substitution at position 6 (replacing native GnRH's glycine) and a des-glycine-10 ethylamide C-terminal modification, in which the native terminal glycinamide is replaced by direct ethylamide attachment to proline-9. This is the same general modification strategy used by Alarelin (D-alanine-6) and structurally related to Triptorelin's D-tryptophan-6 approach, both also built on this site — three chemically distinct single-amino-acid substitutions at the same sequence position, each defining a separately developed, separately branded compound.

At Verified Peptides, we think Leuprolide is likely the single most widely recognized and longest-established GnRH agonist analog in clinical use worldwide. It was first FDA-approved in 1985 (as Lupron) for the palliative treatment of advanced prostate cancer, making it one of the earliest GnRH agonist analogs to reach the US market. Its approved indications have since expanded substantially to include endometriosis (alone and in combination with norethindrone acetate), preoperative management of anemia caused by uterine fibroids, and central precocious puberty in children. It is marketed under numerous brand names and formulations, including Lupron, Lupron Depot, Eligard, and Camcevi, spanning daily injection, and 1-, 3-, 4-, and 6-month depot formulations.

Chemically, Leuprolide Acetate (the monoacetate salt commonly sold) has molecular formula C61H88N16O14, molecular weight approximately 1269.47 g/mol, CAS number 74381-53-6, PubChem CID 657180. We independently cross-calculated the free-base peptide's formula (before acetate salt formation) as C59H84N16O12, molecular weight approximately 1209.4 g/mol, and confirmed that adding one acetic acid equivalent (accounting for the monoacetate salt form, unlike Alarelin's diacetate) reproduces the reported acetate salt formula and molecular weight exactly.

To derive the free-base formula, we summed the constituent free amino acid formulas for the nine residues (glutamic acid, histidine, tryptophan, serine, tyrosine, D-leucine, leucine, arginine, and proline), subtracted eight water molecules for the eight peptide-bond condensations, then applied pyroglutamate cyclization (removing one further water molecule) and C-terminal ethylamidation (net addition of one nitrogen, two carbons, and five hydrogens, with removal of one oxygen and one hydrogen from the original carboxylic acid). This reproduced C59H84N16O12 for the free base, and adding one acetic acid equivalent (C2H4O2) yielded C61H88N16O14, matching the vendor-reported acetate salt formula exactly — a clean, internally consistent result, in contrast to a formula/weight mismatch we identified and had to correct for Alarelin elsewhere in this phase.

At Verified Peptides, we think Leuprolide Acetate has one of the most extensive clinical evidence bases of any compound in this catalog, reflecting nearly four decades of continuous clinical use and ongoing formulation development. Beyond the Sharifi and Browneller (2002, PMID 12187208) depot-comparison study discussed in the mechanism section, Leuprolide's broader clinical trial literature spans multiple generations of depot formulation development (1-month, 3-month, 4-month, and 6-month sustained-release products), each independently required to demonstrate testosterone suppression efficacy (typically defined as maintaining serum testosterone below a castrate threshold, commonly 50 ng/dL and more recently sometimes 20 ng/dL in newer trials) through dedicated Phase III clinical programs, in addition to separate clinical trial programs supporting its endometriosis, uterine fibroid-related anemia, and central precocious puberty indications.

We want to note that this breadth of independently required, formulation-specific clinical trial data reflects a general regulatory principle relevant to understanding sustained-release peptide drugs broadly: because different depot formulations (differing in polymer matrix, injection route, or release duration) can have meaningfully different pharmacokinetic profiles despite delivering the identical active peptide, regulatory approval of a new depot formulation typically requires its own dedicated clinical demonstration of efficacy, rather than relying solely on the active peptide's prior approval in a different formulation. This is a useful general principle for researchers to understand when evaluating any peptide drug sold in multiple different sustained-release formats.

At Verified Peptides, we sell research-grade Leuprolide Acetate exclusively for laboratory research, and we think this compound, alongside Triptorelin, represents the strongest and most extensively documented evidence tier in this entire catalog, reflecting genuine, decades-long, multiply-regulatory-reviewed clinical use rather than any single study or manufacturer claim.

We also want to note that testosterone suppression thresholds used to define successful treatment have themselves evolved over Leuprolide's clinical history: earlier trials commonly used a castrate threshold of 50 ng/dL, a value originally derived from the historical precision limits of older testosterone assays and from comparison to surgical castration (orchiectomy) outcomes, while newer research has increasingly used a stricter 20 ng/dL threshold, reflecting improved assay sensitivity and evidence that even sub-50 ng/dL testosterone levels can meaningfully affect prostate cancer outcomes. This evolution in outcome-measurement standards is a genuine, independently documented methodological development relevant to interpreting and comparing Leuprolide efficacy data across different eras of publication.

Leuprolide Acetate's original 1985 FDA approval for advanced prostate cancer predates the modern era of large multinational randomized controlled trials as the standard evidentiary bar, meaning its earliest approval relied on evidentiary standards somewhat different from what would be expected for a new drug application today — though its subsequent decades of use, expanded indications, and newer depot formulations have each been supported by more contemporary randomized and controlled trial designs, effectively building a substantially more rigorous evidence base over time than existed at initial approval.

The development of increasingly long-acting depot formulations (from monthly to 6-month release) for Leuprolide and related GnRH agonists reflects an ongoing pharmaceutical engineering priority around treatment adherence: patients receiving injections for chronic conditions like prostate cancer, which often require years of continuous GnRH agonist therapy, are more likely to maintain consistent treatment with fewer, more widely spaced injections, a patient-adherence rationale that has driven much of the formulation innovation across this entire drug class.

Leuprolide Acetate is also studied and used off-label or in specific regional approvals for additional applications beyond its primary approved indications, including in some gender-affirming care protocols and, historically, in certain fertility treatment protocols for controlled ovarian stimulation timing in IVF — applications that rely on the same fundamental gonadotropin-suppression mechanism applied to different clinical goals, similar to the pattern described in this catalog's Triptorelin profile.

At Verified Peptides, we require independent third-party HPLC purity testing and mass spectrometry identity confirmation for every batch of research-grade Leuprolide Acetate we offer, with a Certificate of Analysis (COA) available for each lot. As a peptide with a D-amino acid substitution, pyroglutamate N-terminus, and C-terminal ethylamide modification, all three features should be confirmed as part of identity testing, since the specific D-leucine-6 substitution is what distinguishes Leuprolide from closely related GnRH agonist analogs with different position-6 substitutions.

We source exclusively from manufacturers operating under Good Manufacturing Practice (GMP)-aligned quality systems, and every lot is independently verified rather than accepted solely on a supplier's internal documentation. Researchers should always request and review the specific COA for the lot they receive, confirming purity percentage and molecular identity before use in any experimental protocol.

Lyophilized Leuprolide Acetate is stable when stored at -20°C, protected from light and moisture. At Verified Peptides, we ship lyophilized peptide with appropriate cold-chain packaging to preserve stability in transit.

Once reconstituted, solution should be stored refrigerated at 2–8°C and used within the timeframe indicated on the product's documentation, avoiding repeated freeze-thaw cycles. Researchers should note that the approved clinical depot formulations (biodegradable polymer microsphere or in situ gel-forming sustained-release products) involve specialized pharmaceutical manufacturing processes not replicated in standard research-grade lyophilized peptide, which is intended for direct research use rather than sustained-release formulation development.