TH9507, developed under the laboratory code TH9507, is a synthetic analog of growth-hormone-releasing hormone (GHRH) built on the same 29-amino-acid GHRH(1-29) backbone that sermorelin uses, with an added trans-3-hexenoic acid group attached at the N-terminus. Researchers designed that modification for one specific reason: native GHRH fragments are rapidly cleaved by the enzyme dipeptidyl peptidase IV (DPP-IV), and the added group sterically blocks that cleavage site. The result is a GHRH receptor agonist that behaves like the parent fragment in receptor-binding terms but persists longer against enzymatic degradation, which is why it shows up in the literature as a "stabilized" GHRH analog rather than a redesigned receptor ligand.
| Attribute | Detail |
|---|---|
| Name | TH9507, laboratory code TH9507 |
| Class | Modified 29-amino-acid GHRH(1-29) analog with an N-terminal trans-3-hexenoic acid group |
| Target | Growth-hormone-releasing hormone receptor (GHRHR), same receptor sermorelin engages |
| Design rationale | N-terminal modification sterically hinders cleavage by dipeptidyl peptidase IV (DPP-IV) |
| What studies examine | Nonclinical pharmacology and safety pharmacology, plasma metabolism of GHRH analogs, translational tissue and transcriptomic studies |
| Form supplied | Lyophilized powder, research use only |
Why does GHRH need to be stabilized against DPP-IV?
Dipeptidyl peptidase IV, also known as CD26, is a widely expressed enzyme that cleaves peptide bonds two residues from the N-terminus of many regulatory peptides, and Mentlein's 1999 review catalogs GHRH among the substrates it inactivates this way. Because GHRH(1-29) fragments like sermorelin present that same vulnerable N-terminal structure, they are subject to rapid enzymatic breakdown in plasma. Kubiak et al. (1994) examined the metabolism of mouse GHRH and a series of related bovine GRF analogs in mouse and bovine plasma in vitro, mapping which structural positions were most susceptible to cleavage and providing part of the groundwork later analog-design work drew on.
How is TH9507's structure different from sermorelin's?
TH9507 retains the same 29-residue GHRH backbone used in sermorelin research but adds a trans-3-hexenoic acid group at the N-terminal end. That single addition is reported to hinder DPP-IV access to the cleavage site without altering how the rest of the molecule engages the GHRH receptor. Researchers studying the two compounds side by side generally treat TH9507 as a chemically reinforced version of the same GHRH(1-29) pharmacophore that sermorelin represents, rather than as a structurally distinct receptor ligand; see what is sermorelin for the unmodified fragment this analog is built from.
What do receptor-binding assays show about the modification?
Structure-activity work on the GHRH(1-29) backbone, including the pharmacophore mapping Lefrançois and Gaudreau carried out in rat adenopituitary tissue and the superfusion bioassay system Rekasi and Schally developed for comparing GHRH analogs, established which regions of the sequence are required for receptor engagement versus which regions tolerate substitution without loss of activity. The N-terminal region modified in TH9507 sits outside the core residues those pharmacophore studies identified as essential for receptor contact, which is consistent with the pharmacology findings that the trans-3-hexenoic acid addition does not meaningfully change receptor affinity relative to the unmodified GHRH(1-29) fragment, while changing how quickly the molecule is degraded once introduced into a biological matrix. Researchers characterizing new GHRH analogs generally test both properties, receptor engagement and enzymatic stability, as separate assay endpoints rather than assuming one predicts the other.
What did nonclinical pharmacology studies examine?
Ferdinandi et al. (2007) reported the nonclinical pharmacology and safety evaluation of TH9507, covering receptor-binding characteristics, pharmacokinetic behavior, and safety pharmacology endpoints gathered across the animal studies conducted to characterize the compound ahead of clinical development. That paper remains the primary reference researchers cite for TH9507's preclinical pharmacology profile, distinct from the later clinical literature that examined the compound in human trials. The pharmacokinetic comparisons in that paper are also the reference point researchers use when contrasting TH9507's persistence in plasma against the more rapid clearance reported for unmodified GHRH(1-29) fragments in the Kubiak metabolism studies described above.
What has translational tissue research examined?
Beyond receptor pharmacology, researchers have used TH9507 as a probe for studying growth-hormone-axis effects at the tissue level. Fourman et al. (2020) examined hepatic transcriptomic signatures using liver tissue sampling in a study of TH9507 and hepatic fat, applying RNA-sequencing methods to identify which gene-expression pathways shifted in association with the growth-hormone axis. Work of this kind treats TH9507 as a tool for probing GHRH-receptor-linked signaling in a specific tissue rather than as a subject of dosing guidance, and the pooled clinical trial data summarized by Falutz et al. (2010) has been a reference point for the receptor-level pharmacodynamics researchers cite when describing how sustained GHRH receptor engagement is reflected in downstream physiology.
How does TH9507 fit alongside other growth-hormone-axis research peptides?
TH9507, sermorelin and ghrelin-receptor secretagogues such as ipamorelin all intersect with growth-hormone-axis research but occupy different positions in the pathway. Sermorelin and TH9507 both act on the GHRH receptor upstream of GH release, differing mainly in metabolic stability rather than receptor pharmacology, while ipamorelin acts on a separate receptor, the GH secretagogue receptor; that comparison is laid out in what is ipamorelin and summarized across the whole class in growth hormone secretagogues in research.
Frequently asked questions
Is TH9507 the same molecule as sermorelin?
No, but they are closely related. Both use the 29-amino-acid GHRH(1-29) sequence, but TH9507 adds a trans-3-hexenoic acid group at the N-terminus specifically to hinder DPP-IV cleavage, a modification sermorelin does not carry.
Why is DPP-IV relevant to GHRH-analog research?
DPP-IV is an enzyme that cleaves many regulatory peptides near their N-terminus, and native GHRH fragments are a documented substrate. Researchers designing stabilized analogs like TH9507 target this cleavage site directly, and studies such as Kubiak et al. (1994) characterized the metabolic vulnerability that motivated the design.
What receptor does TH9507 act on?
The growth-hormone-releasing hormone receptor (GHRHR), the same class B G-protein-coupled receptor that sermorelin and native GHRH engage on pituitary somatotroph cells, first cloned and characterized in the pituitary-specific receptor work described above.
What did the nonclinical pharmacology studies on TH9507 cover?
Ferdinandi et al. (2007) reported receptor pharmacology, pharmacokinetic behavior and safety pharmacology findings gathered in the animal studies conducted to characterize TH9507 ahead of later clinical research.
Does the N-terminal modification change how TH9507 binds its receptor?
Structure-activity mapping of the GHRH(1-29) backbone places the modified region outside the residues identified as essential for receptor contact, and pharmacology studies report comparable receptor engagement between TH9507 and unmodified GHRH(1-29), with the main documented difference being resistance to enzymatic cleavage rather than a change in how the molecule sits in the receptor binding pocket itself.
How is TH9507 supplied for laboratory use?
As a lyophilized powder intended for research use only, sold by lot with an accompanying certificate of analysis. See our TH9507 lot page for current specifications.
References
- Ferdinandi ES, Brazeau P, High K, et al. Non-clinical pharmacology and safety evaluation of TH9507, a human growth hormone-releasing factor analogue. Basic Clin Pharmacol Toxicol. 2007;100(1):49-58. PubMed 17214611.
- Kubiak TM, Martin RA, Leone JW, et al. Metabolism of mouse growth hormone-releasing factor, mGRF(1-42)OH, and selected analogs from the bovine GRF series in mouse and bovine plasma in vitro. Pept Res. 1994;7(3):153-161. PubMed 7915920.
- Mentlein R. Dipeptidyl-peptidase IV (CD26), role in the inactivation of regulatory peptides. Regul Pept. 1999;85(1):9-24. PubMed 10588446.
- Mayo KE. Molecular cloning and expression of a pituitary-specific receptor for growth hormone-releasing hormone. Mol Endocrinol. 1992;6(10):1734-1744. PubMed 1333056.
- Falutz J, Mamputu JC, Potvin D, et al. Effects of TH9507 (TH9507), a growth hormone-releasing factor analog, in HIV-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010;95(9):4291-4304. PubMed 20554713.
- Fourman LT, Billingsley JM, Agyapong G, et al. Effects of TH9507 on hepatic transcriptomic signatures in HIV-associated NAFLD. JCI Insight. 2020;5(16):e140134. PubMed 32701508.
Research use only. Homegrown Peptides products are for laboratory research and are not for human or animal use. Nothing in this article is medical advice.
