PX1-S

What is PX1-S?

PX1-S is a synthetic 31-amino-acid analog of human glucagon-like peptide-1 (GLP-1), modified with an aminoisobutyric acid substitution at position 8 and a C18 fatty diacid chain attached via a spacer at lysine 26. Those modifications confer resistance to dipeptidyl peptidase-4 (DPP-4) cleavage and promote reversible albumin binding, giving the molecule a markedly extended half-life relative to native GLP-1.

PX1 Research supplies lyophilized PX1-S as a reference standard for receptor pharmacology, analytical method development and comparative incretin research. It is one of the most frequently cited GLP-1 analogs in the peer-reviewed literature and is commonly used as the benchmark against which newer dual and triple agonists are characterized.

Mechanism of action

PX1-S is a selective agonist at the class B G-protein-coupled GLP-1 receptor. Receptor occupancy drives Gs-coupled adenylate cyclase activation and cAMP accumulation, with downstream protein kinase A and Epac2 signaling. In pancreatic beta-cell models this potentiates glucose-dependent insulin secretion; in central nervous system models the receptor is expressed in hypothalamic and hindbrain nuclei associated with appetite regulation.

In laboratory characterization, PX1-S is typically profiled in cAMP accumulation assays, β-arrestin recruitment panels and receptor internalization studies, where its bias profile and prolonged residence time distinguish it from native GLP-1 and from short-acting analogs such as exenatide.

Research history

PX1-S entered the literature with Lau and colleagues in 2015, who described the acylation strategy and the resulting pharmacokinetic profile. It has since become a standard comparator across metabolic, cardiovascular and neuroscience research programs.

Because so much comparative data exists, PX1-S is routinely included as a positive control when characterizing newer incretin polyagonists such as PX12-T and PX13-R.

Laboratory handling and storage

PX1-S ships as a lyophilized powder in a sealed, tamper-evident vial. Store the unopened vial between −20°C and −80°C, protected from light, until the day of use. In this state the peptide is stable through the labeled expiration date printed on the lot documentation.

Purity, testing and Certificate of Analysis

Every PX1 Research lot of PX1-S is manufactured in the United States and released against a documented specification of ≥99% purity by reversed-phase HPLC, with identity confirmed on the same lot by high-resolution LC-MS against the theoretical mass of the sequence.

Research use only

PX1-S supplied by PX1 Research is intended strictly for in-vitro laboratory and research applications. It is not a drug, food, cosmetic, or medical device, and it is not for human or veterinary use, diagnosis, treatment, or consumption.

Researchers are responsible for handling the compound in accordance with their institution's safety procedures and all applicable local regulations. Safety data sheets and current lot documentation are available on this site.

Purity, identity and certificate of analysis

PX1-S is a 31-residue GLP-1 receptor agonist carrying an aminoethoxy-acetyl spacer and a C18 fatty di-acid side chain at position 26. Because that side chain dominates the molecule's chromatographic behavior, a shallow reversed-phase HPLC gradient is required to separate the intact compound from des-acyl and positional-isomer impurities that co-elute on a fast generic method. PX1 reports purity for the specific lot in the vial at ≥99% by reversed-phase HPLC, not as a family specification.

Identity is confirmed by liquid chromatography-mass spectrometry against the theoretical monoisotopic mass of the acylated 31-mer. This step matters more for acylated analogs than for short unmodified peptides: a lot that lost part of its side chain still reads as a peptide of roughly the right length on a coarse method, while behaving in receptor work far more like native GLP-1 than like PX1-S.

Each lot also carries endotoxin by kinetic chromogenic LAL, residual solvent screening by gas chromatography and water content by Karl Fischer titration. Water content and net peptide content together determine how much peptide is actually present per labelled milligram, which is the figure a laboratory needs when preparing a reference standard — purity alone does not answer it.

How PX1-S compares to PX12-T and PX13-R

PX1-S is a single-receptor GLP-1 agonist. PX12-T is a dual GLP-1 / GIP agonist, and PX13-R is a single-molecule triple agonist adding a glucagon receptor arm. Comparative in-vitro designs use all three precisely because they share a design lineage: the incretin backbone and the lipidation strategy are conserved, so differences in receptor engagement can be attributed to the added receptor arms rather than to unrelated structural changes.

For analytical method development the three are frequently run on the same gradient. They are close enough in hydrophobicity to challenge a method's specificity, which makes a mixed standard a useful system-suitability check when a laboratory needs to demonstrate that its method can distinguish the class rather than simply detect it.

PX1 supplies all three as separate reference compounds with lot-matched certificates. Nothing on this page should be read as a comparison of clinical effect; the comparison described here is a structural and analytical one relevant to bench work only.

Common research questions about PX1-S

Why does PX1 list PX1-S as PX1-S? The brand code appears on the vial, the label and at checkout for catalogue continuity, while the monograph, the certificate of analysis and all analytical documentation use the canonical name PX1-S. The two identifiers refer to the same material and the same lot.

What purity is appropriate for receptor pharmacology? ≥98% by reversed-phase HPLC is the working floor and ≥99% is the practical standard, because the characteristic impurities in an acylated GLP-1 analog are closely related structures that may retain partial receptor activity. Such impurities contaminate the pharmacology rather than merely diluting the sample, which is why the impurity profile matters as much as the headline number.

How is a lot verified on receipt? Confirm the lot number on the vial matches the certificate, confirm the certificate carries the actual chromatogram and mass spectrum rather than a summary table, and confirm the reported mass matches the theoretical mass within instrument tolerance. A lot failing any of the three is treated as uncharacterized regardless of the stated purity.

Is PX1-S stable in solution? Less so than short unmodified peptides. The ester-free acyl linkage is chemically robust, but the molecule's surface activity means the dominant loss mechanism in dilute aqueous solution is physical — adsorption and aggregation — rather than hydrolysis. That is why handling practice, not just storage temperature, determines whether a solution still holds its nominal concentration a week later.