Ularitide Acetate | CAS 118812-69-4 | Natriuretic Peptide Receptor Agonist (Research Use Only) | Knowlux
Product Description
Ularitide Acetate, CAS 118812-69-4, is a synthetic 32-amino-acid natriuretic peptide corresponding to human urodilatin, supplied by Knowlux for laboratory research use. Urodilatin is the renal form of atrial natriuretic peptide (ANP), distinguished from circulating ANP(1-28) by a four-amino-acid N-terminal extension (Thr-Ala-Pro-Arg). The sequence is H-Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH, with a disulfide bridge between Cys11 and Cys27. The free peptide molecular formula is C145H234N52O44S3 (MW 3505.97); the acetate salt corresponds to C145H234N52O44S3.C2H4O2 (MW 3565.98). Each lot is released with a lot-specific COA, MSDS and analytical traceability.
CAS and Salt Form Clarification: Ularitide presents two distinct CAS registries that are frequently conflated in commercial listings. CAS 118812-69-4 is the acetate salt registry most consistently applied across NCI Thesaurus, NCATS Inxight, ChemicalBook, and the majority of suppliers, and is associated with the acetate formula C145H234N52O44S3.C2H4O2 and MW 3565.98. CAS 115966-23-9 appears across AbMole, BOC Sciences, LKT Labs, and several catalogue listings under the product names Ularitide or Urodilatin (human); these listings pair 115966-23-9 with the free-peptide formula C145H234N52O44S3 and MW 3505.97. The practical relationship is that 118812-69-4 is the acetate salt and 115966-23-9 is the free peptide, but the two registries are applied interchangeably in catalogue copy. Buyers should treat the CAS number as an identifier for the compound family rather than as a definitive statement of salt form, and should confirm which registry and which molecular weight (3505.97 versus 3565.98) are declared on the lot COA before quantitative use.
Structural and Functional Note: The four-residue N-terminal extension is the defining structural feature of Ularitide relative to ANP(1-28), and it is the structural basis for the peptide's resistance to neutral endopeptidase 24.11 (NEP). Circulating ANP is rapidly degraded by NEP, and NEP activity is increased in decompensated heart failure; the N-terminal extension in urodilatin confers resistance to this inactivation, resulting in a more potent and longer-acting natriuretic effect than ANP in comparative studies. Ularitide retains the 17-residue disulfide-linked ring (Cys11-Cys27) conserved across the natriuretic peptide family. The peptide contains a methionine residue at position 17, an oxidation liability; the Cys11-Cys27 bridge is a reducible disulfide and is sensitive to reducing agents.
Product Parameters
| Item | Specification |
|---|---|
| Product Name | Ularitide Acetate |
| Synonyms | Urodilatin (human); ANP (95-126); Atrial Natriuretic Factor Prohormone (95-126); Ularitide |
| CAS No. | 118812-69-4 (acetate salt); 115966-23-9 (free peptide, as applied in several catalogues) |
| Molecular Formula | C145H234N52O44S3 (free peptide); C145H234N52O44S3.C2H4O2 (acetate salt) |
| Molecular Weight | 3505.97 g/mol (free peptide); 3565.98 g/mol (acetate salt) |
| Sequence (1-letter) | TAPRSLRRSSCFGGRMDRIGAQSGLGCNSFRY (disulfide bridge Cys11-Cys27) |
| Sequence (3-letter) | H-Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr-OH (disulfide bridge Cys11-Cys27) |
| Sequence Length | 32 amino acids, cyclic (single disulfide bridge) |
| Key Structural Features | Four-residue N-terminal extension (Thr-Ala-Pro-Arg); disulfide bridge Cys11-Cys27; Met17 thioether; free N-terminus; free C-terminal Tyr-OH |
| InChIKey | KICHBVZYZBOCOQ-TYLLENITSA-N (acetate); IUCCYQIEZNQWRS-DWWHXVEHSA-N (free peptide) |
| Appearance | White to off-white lyophilized powder |
| Solubility | DMF 25 mg/mL; DMSO 10 mg/mL; ethanol 0.3 mg/mL; PBS 10 mg/mL (see Solubility section) |
| Purity | >=98.0% (HPLC); >=99.0% available |
| Identity | Confirmed by LC-MS |
| Grade | Research grade |
| Counter-ion | Acetate (lot-specific, declared on COA) |
| Acetate Content | 5.0% to 12.0% (supplier specification) |
| Peptide Content | >=80.0% (supplier specification) |
| Water Content | <=8.0% (supplier specification) |
| Single Impurity | <=1.0% (HPLC; reference grade) |
| Storage | See Storage and Stability section |
| Packaging | 1 mg / 5 mg / 10 mg / 50 mg / 100 mg vial; bulk on request |
| Application | Laboratory research use only |
| Origin | China |
Product Details
1. Overview
Ularitide is a synthetic form of urodilatin, a 32-residue natriuretic peptide synthesized in the distal tubular cells of the kidney and thought to act as a local regulator of sodium and water excretion. It belongs to the natriuretic peptide family alongside ANP, BNP, and CNP, and shares with ANP the conserved 17-residue disulfide-linked ring required for receptor activation. The peptide binds natriuretic peptide receptor A (NPR-A, also designated GC-A), a particulate guanylyl cyclase, and elevates intracellular cGMP, producing vasodilation, natriuresis, and diuresis, and suppressing the renin-angiotensin-aldosterone system. Ularitide was developed clinically for acute decompensated heart failure and was evaluated in the SIRIUS I and TRUE-AHF trials; it has not received marketing approval in the United States or the European Union. The material supplied under this specification is research-grade and is not intended for human administration.
2. Receptor Pharmacology and NEP Resistance
Ularitide's pharmacology is distinguished from ANP(1-28) by a modestly different receptor affinity profile and a substantially improved resistance to enzymatic degradation. In rat mesangial cells, Ularitide competes with high affinity for the non-guanylate cyclase-coupled ANPR-C receptor with an IC50 of approximately 70 pM, but with lesser affinity for the guanylate cyclase-linked ANPR-A receptor with an IC50 of approximately 800 pM. In papillary collecting duct homogenates, which possess only ANPR-A receptors, the apparent Kd for Ularitide is 2.7 nM, compared with 229 pM for alpha-ANP, indicating approximately 12-fold lower intrinsic affinity for ANPR-A in this tissue preparation. The functional consequence is offset by the peptide's resistance to NEP: the four-amino-acid N-terminal extension is the structural basis for enhanced stability against neutral endopeptidase 24.11, and this resistance translates into a more potent and longer-acting natriuretic effect than ANP in comparative models.
3. Research Applications
Published pharmacological characterizations and clinical trial data describe the following research applications:
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NPR-A/GC-A binding and functional assays (cGMP accumulation in renal and vascular cell models)
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ANPR-C (clearance receptor) binding and metabolic clearance studies
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Cardiorenal physiology and natriuresis/diuresis mechanism research
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Heart failure and acute decompensated heart failure research models (SIRIUS I and TRUE-AHF trial contexts)
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Renal dopamine metabolism and dopaminergic regulation studies
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Comparative pharmacology of ANP, urodilatin, and BNP family peptides, with emphasis on NEP resistance
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Peptide stability and methionine oxidation studies (Met17 as an oxidation hotspot)
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Reference standard development for HPLC and LC-MS analytical methods
In the TRUE-AHF phase III trial (n = 2157), Ularitide was associated with less worsening of heart failure at 48 hours and a 47% decline in pro-BNP compared with placebo, but it did not affect the clinical composite endpoint or reduce long-term cardiovascular mortality (21.7% versus 21.0%; HR 1.03; 96% CI 0.85-1.25). In SIRIUS I, Ularitide produced a dose-dependent decrease in systolic blood pressure, with 16% of patients in the 30 ng/kg/min group experiencing hypotension. These trial observations are provided for scientific context and do not constitute clinical guidance.
Quality Control
| Test Item | Method | Acceptance Criteria |
|---|---|---|
| Purity | RP-HPLC | >=98.0% (standard); >=99.0% available |
| Identity | LC-MS | Consistent with structure (3565.98 +/- 1 for acetate) |
| Single Impurity | RP-HPLC | <=1.0% |
| Peptide Content | Nitrogen analysis (%N) | >=80.0% |
| Acetate Content | HPLC or ion chromatography | 5.0% to 12.0% |
| Water Content | Karl Fischer | <=8.0% |
| Appearance | Visual | White to off-white powder |
ChemicalBook's quality specification for Ularitide Acetate provides the clearest reference standard: white powder appearance, HPLC purity >=98.0%, acetate content 5.0%-12.0%, water content <=8.0%, and peptide content >=80.0%. BenchChem lists >=98% HPLC purity with full analytical documentation. Conscientia Industrial specifies >=98.0% purity for its high-purity Ularitide API. A Chinese supplier listing reports 99% by HPLC-MS. AbMole lists a standard of >99.0% for its catalogue item. The principal quality consideration is the salt-form ambiguity discussed in the CAS Clarification: a lot reported at MW 3505.97 is on a free-peptide basis, whereas a lot at 3565.98 is on the acetate-salt basis. Researchers preparing molar solutions should use the peptide content value and the declared salt basis rather than the HPLC purity figure alone. Full COA, MSDS, and lot-specific chromatograms are issued with each shipment.
Solubility and Handling
Solubility: Ularitide Acetate solubility is best documented in the AbMole batch-tested dataset, which reports DMF 25 mg/mL, DMSO 10 mg/mL, ethanol 0.3 mg/mL, and PBS (pH 7.2) 10 mg/mL at 25C. LKT Labs describes the compound as soluble in water, DMSO, and DMF. The ethanol solubility of 0.3 mg/mL is notably low and should not be assumed adequate for stock preparation. For practical stock preparation, DMF at 25 mg/mL is the highest consistently supported concentration, followed by DMSO and PBS at 10 mg/mL. AbMole's technical guidance notes that hygroscopic DMSO significantly affects solubility and recommends freshly opened DMSO; stock solutions should be aliquoted in tightly sealed vials and used within 1 month. For in vivo work, working solutions should be prepared fresh on the day of use, and sonication or gentle warming can be used to assist dissolution if precipitation is observed. Prepare solutions fresh and avoid repeated freeze-thaw cycles.
Handling Precautions: Use powder-handling containment (glove box or fume hood with particulate control). Avoid inhalation of fine powder. Wear nitrile gloves, lab coat, and eye protection. The Met17 residue is susceptible to oxidation; protect from prolonged exposure to air and light. The Cys11-Cys27 disulfide bridge is sensitive to reducing agents; avoid contact with dithiothreitol (DTT) or mercaptoethanol. A US patent filing on lyophilized natriuretic peptide formulations notes that water in the lyophilized cake accelerates product degradation, which reinforces the importance of desiccated storage.
Storage and Stability
| Format | Temperature | Shelf Life |
|---|---|---|
| Lyophilized Powder | -20C, sealed, desiccated, protected from light | 3 years (TargetMol); recommended long-term condition (AbMole, ChemicalBook, LKT Labs) |
| Lyophilized Powder | 2C to 8C, sealed, refrigerated | Recommended for maintaining stability of the lyophilized powder (US patent filing) |
| Reconstituted Solution | -80C, aliquoted, sealed | 1 year (TargetMol) |
| Reconstituted Solution | -20C, aliquoted, sealed | 1 month (general guidance for research peptides) |
| In-use infusion (clinical context) | Ambient temperature | Up to 24 h prior to infusion and for the subsequent 24-h infusion period (NEJM in-use stability data) |
Storage guidance for Ularitide Acetate converges on -20C for the lyophilized powder as the standard research condition, with desiccation and protection from light. TargetMol specifies 3 years at -20C for powder and 1 year at -80C for solutions. AbMole and ChemicalBook specify -20C with freeze-drying and light protection. LKT Labs specifies -20C. A US patent filing on room-temperature-stable lyophilized natriuretic peptide formulations states that the lyophilized powder must be refrigerated at 2C-8C to maintain stability and that water in the lyophilized cake accelerates degradation; this is a more conservative storage recommendation than the -20C condition used by most research suppliers, and it suggests that 2C-8C is a viable alternative where -20C is not available, provided the powder remains desiccated. For reconstituted solutions, the stability window is short; the NEJM in-use stability data for the clinical infusion applies to a formulated product and should not be extrapolated to research stock solutions without independent validation. The lyophilized powder is hygroscopic; equilibrate vials to room temperature before opening to prevent condensation.
Documentation Support
Per lot: COA, MSDS, HPLC chromatogram, and mass spectrometry data. Acetate content, water content, peptide content, and salt-form stoichiometry available on request. Custom specifications and third-party inspection can be arranged on a project basis.
About Knowlux
Knowlux Biotechnology is a GMP-oriented manufacturer and supplier of peptides, APIs and fine-chemical research compounds, operating from Hubei, China. We serve research groups, CDMOs and distributors in more than 40 countries, and support contract synthesis, custom packaging and technical documentation requests.
Compliance Statement
FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT FOR DIAGNOSTIC OR THERAPEUTIC USE.
This product is supplied for laboratory research use only. It is not for human or animal administration, not for diagnostic or therapeutic use, not for retail sale, and not for personal use. Ularitide Acetate has been investigated in clinical trials for acute decompensated heart failure but is not approved as a medicinal product in the United States or the European Union; the material offered under this specification is research-grade and is not intended for clinical use. The purchaser is responsible for verifying product specifications against their specific research requirements and for compliance with all applicable institutional, local, and national regulations governing research chemical acquisition, storage, and use. Research context statements are for scientific reference only and do not constitute medical advice, promotional claims, or dosing guidance.
Data Verification Notes
The free peptide formula C145H234N52O44S3 and MW 3505.97 are confirmed by NCI Thesaurus, ChemicalBook, Adooq, PeptideDB, and BenchChem. The acetate salt formula C145H234N52O44S3.C2H4O2 and MW 3565.98 are confirmed by NCATS Inxight under CAS 118812-69-4. The sequence Thr-Ala-Pro-Arg-Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr with the Cys11-Cys27 disulfide bridge is confirmed by ChemicalBook, Adooq, PeptideDB, and Guide to Pharmacology. The CAS mapping (118812-69-4 = acetate; 115966-23-9 = free peptide) is inferred from the consistent pairing of 118812-69-4 with the acetate formula and 115966-23-9 with the free-peptide formula across NCATS Inxight, AbMole, BOC Sciences, and LKT Labs; the two registries are frequently used interchangeably in catalogue copy and are flagged rather than reconciled into a single identifier. The NEP-resistance mechanism and the N-terminal extension as its structural basis are from NCATS Inxight, ScienceDirect, and BenchChem. The receptor affinity data (ANPR-C IC50 ~70 pM; ANPR-A IC50 ~800 pM; ANPR-A Kd 2.7 nM for Ularitide versus 229 pM for alpha-ANP) are from the CPRiL-curated primary study. Solubility values are from AbMole's batch-tested dataset. The TRUE-AHF efficacy and mortality data are from the ESC Heart Failure Association scientific statement and the ScienceDirect overview. The SIRIUS I blood pressure and hypotension data are from the NEJM and JACC sources. The storage guidance divergence (-20C versus 2C-8C) is reported as-is, with the 2C-8C condition attributed to the US patent filing and the -20C condition attributed to the research-peptide suppliers.
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