Vixticibart  (Synonyms: REGN-5381)

Vixticibart (REGN-5381) is a fully human IgG4 monoclonal antibody and NPR1 agonist that targets NPR1. Vixticibart stabilizes the receptor in an activated conformation by binding to the N-terminal domain of NPR1, and enhances the activity of endogenous ligands ANP and BNP without blocking ligand binding when these ligands are present. Vixticibart exerts vasodilatory and hypotensive effects by inducing cGMP production, preferentially dilating venous vessels to reduce systolic and venous pressure, but does not induce diuresis and may trigger a compensatory increase in heart rate. Vixticibart produces a synergistic hypotensive effect when combined with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and is currently mainly used in research related to heart failure and hypertension^[1][2][3].

Human IgG4 kappa

Human IgG4 (S228P) kappa, Isotype Control

Human

NPR1

Vixticibart specifically binds to human and monkey natriuretic peptide receptor 1 extracellular domain proteins, with no cross-reactivity to mouse natriuretic peptide receptor 1, natriuretic peptide receptor 2, or natriuretic peptide receptor 3, and does not interfere with atrial natriuretic peptide binding to human natriuretic peptide receptor 1^[1].
Vixticibart (10^-12 to 10^-6 M; under conditions supporting binding) dose-dependently binds to human and monkey natriuretic peptide receptor 1-expressing HEK293 cells, with enhanced binding in the presence of atrial natriuretic peptide or brain natriuretic peptide, and EC₅₀ values ranging from 2.27 to 5.69 nM^[1].
Vixticibart (10^-15 to 10^-5 M) dose-dependently agonizes human and monkey natriuretic peptide receptor 1 in a calcium flux bioassay, with EC₅₀ values ranging from 42.5 to 82.2 nM, and achieves maximum activation comparable to natriuretic peptide ligands at high concentrations^[1].
Vixticibart (10^-14 to 10^-5 M) dose-dependently activates human natriuretic peptide receptor 1 to induce cGMP accumulation in HEK293 cells, acts as a partial agonist relative to natriuretic peptide ligands, and shows enhanced activation in the presence of low concentrations of atrial natriuretic peptide or brain natriuretic peptide^[1].
Vixticibart (molar excess; overnight at 4°C) binds to the N-terminal domain of human NPR1 dimers, stabilizing an active conformation in the presence of atrial natriuretic peptide and an active-like conformation in the absence of atrial natriuretic peptide, which drives downstream signaling^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Vixticibart (1-50 mg/kg; s.c.; single dose) induces a 10-15 mm Hg reduction in systolic blood pressure in normotensive NPR1^hu/hu mice, with dose-dependent duration of effect lasting up to 28 days for the 50 mg/kg dose^[1].
Vixticibart (25 mg/kg; i.v.; single bolus dose) reduces systolic blood pressure, central venous pressure, and pulmonary arterial pressure, while increasing urinary cGMP levels, in normotensive beagle canines^[1].
Vixticibart (REGN-5381) (25 mg/kg; i.v.; single dose) induces a sustained reduction in systolic blood pressure and increased urinary cGMP in normotensive telemetered beagle dogs following a single 25 mg/kg intravenous dose^[2].
Vixticibart (REGN-5381) (25 mg/kg; i.v.; single dose) reduces central venous pressure and triggers compensatory tachycardia in anesthetized beagle dogs following a single 25 mg/kg intravenous dose^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

4881  [NCBI]

P16066

ELISA, FACS, Functional assay

Unconjugated

The product can be reconstituted/diluted with sterile PBS or saline.

146.16 kDa

2845128-05-2

Liquid

Colorless to light yellow

[Vixticibart]

Shipping with dry ice.

Please refer to the lot-specific COA for specific buffer information.

Please store the product under the recommended conditions in the Certificate of Analysis.

• 
  IgG4-kappa

• [1]. Dunn ME, et al. Agonist antibody to guanylate cyclase receptor NPR1 regulates vascular tone. Nature. 2024;633(8030):654-661.  [Content Brief]

  [2]. Dunn M, et al. A novel agonist antibody to membrane-bound guanylate cyclase receptor, natriuretic peptide receptor 1, induces sustained vasodilation[J]. 2023.

  [3]. Kithcart A P, et al. Effects of REGN5381, a natriuretic peptide receptor 1 agonist antibody, in hypertensive mouse models and mildly hypertensive but otherwise healthy adults in a phase 1 first-in-human study[J]. Journal of the American College of Cardiology, 2024, 83(13_Supplement): 1706-1706.