Antisauvagine-30

Antisauvagine-30 (aSvg-30) is a selective peptide antagonist of the CRF₂ receptor, with an IC₅₀ of 1.1 nM for mouse CRF₂. Antisauvagine-30 modulates cAMP signaling, gastric emptying, food intake, fear conditioning, anxiety-like behavior, stress responses, corticosterone levels, c-Fos expression, and CRF expression. Antisauvagine-30 is used in studies of anxiety-related disorders^{[1][2][3][4][5][6][7]}. IC50 & Target:Kd: 1.4 nM (mouse CRF_2β)
;Kd: 153.6 nM (rat CRF₁)^[1] In Vitro:Antisauvagine-30 (aSvg-30) (90 min) is a CRF₂-selective competitive antagonist with an IC₅₀ of 1.1 nM at mouse CRF₂β receptors and an IC₅₀ of 400 nM at human CRF₁ receptors in stably transfected CHO cell membranes^[1].
Antisauvagine-30 binds with high affinity to CRF2 receptor subtypes (K_i = 0.41-0.8 nM; K_d = 1.4 nM for mouse CRF2b) and with lower affinity to CRF1 receptor subtypes (K_i = 66-170 nM) in transfected HEK293 cell membrane preparations^[2].
Antisauvagine-30 functionally antagonizes CRF₁-mediated cAMP signaling in HEK293-rat CRF₁ cells and Y79 retinoblastoma cells with IC₅₀ values of 1-2 μM^[2].
Antisauvagine-30 (0-1 µM; 60 min) binds with high affinity and strong selectivity to mCRFR2b over rCRFR1 in membrane preparations from transfected HEK 293 cells, with a K_d of 1.4 nM for mCRFR2b^[4].
Antisauvagine-30 (0.01-1 µM; 30 min) is a potent antagonist of Svg-stimulated cAMP production in HEK-mCRFR2b cells with low intrinsic activity, while displaying much weaker antagonist activity in HEK-rCRFR1 cells, consistent with CRFR2b selectivity^[4].
Antisauvagine-30 is a highly selective CRF-R2 ligand with nanomolar affinity for murine CRF-R2b and human CRF-R2α, and negligible affinity for CRF-R1 in recombinant HEK293 cell membrane preparations^[5].
Antisauvagine-30 binds with high affinity to recombinant CRF₂ receptor splice variants (K_d of 0.125 nM for CRF₂(a), K_i of 1.4 nM for CRF₂(b)) and exhibits substantially lower affinity for CRF₁ receptors (K_i of 154 nM at rat CRF₁, no detectable specific binding at human CRF₁), confirming its selectivity as a CRF₂ receptor ligand^[7]. In Vivo:Antisauvagine-30 (3-30 µg/kg; i.p.; single dose; 10 min before Urocortin) dose-dependently antagonizes Urocortin-induced delay of gastric emptying in mice, with partial reversal at 30 µg/kg^[1].
Antisauvagine-30 (100 µg/kg; s.c.; single dose; 3 or 6 h prior to Urocortin) at 100 µg/kg does not significantly antagonize Urocortin-induced delayed gastric emptying when administered 3 or 6 h prior to Urocortin in mice^[1].
Antisauvagine-30 (3 nmol; i.c.v.; single bolus) reduces shock-induced freezing in mice independently of CRF₂ receptor status, with no effect on marble burying or elevated plus-maze measures of anxiety-like behavior^[2].
Antisauvagine-30 (2.70-5.40 nmol/rat; i.c.v.; single dose 15 min before the conditioned fear test) dose-dependently enhances conditioned fear responses, elevates plasma corticosterone, and increases c-Fos and CRF expression in corticolimbic and hypothalamic brain regions of fear-conditioned Wistar rats^[3].
Antisauvagine-30 (30-200 μg/kg; i.p.; single dose 10 min before Urocortin) at 100 μg/kg completely blocks Urocortin-induced inhibition of gastric emptying in mice, while the 30 μg/kg dose produces 54% antagonism^[5].
Antisauvagine-30 (30-200 μg/kg; i.p.; single dose 10 min before Urocortin) only partially reverses Urocortin-induced hypophagia in fasted mice, with ~35% reduction of the inhibitory effect at 100 μg/kg^[5].
Antisauvagine-30 (100 μg/kg; i.p.; single dose 10 min before Urocortin) combined with the CRF-R1 antagonist CP 154526 (HY-12130) does not show enhanced partial reversal of Urocortin-induced hypophagia compared to Antisauvagine-30 alone^[5].
Antisauvagine-30 (400 ng per mouse; bilateral injection into dorsal hippocampus or lateral intermediate septum; 15 min before training alone or 10 min before h/rCRF for combined treatment), a CRFR2-preferring antagonist, blocks septal CRFR2-mediated impairment of fear conditioning and enhances fear conditioning when administered alone into the lateral intermediate septum, while having no effect on hippocampal CRFR1-mediated enhancement of fear conditioning^[6].
Antisauvagine-30 (100 pmol per mouse; bilateral injection into lateral intermediate septum; 10 min before h/rCRF for combined treatment or 30 min before plus-maze test alone) completely blocks CRF-induced anxiety mediated by septal CRFR2 without affecting baseline anxiety levels in mice^[6].
Antisauvagine-30 (bilateral injection into lateral intermediate septum; before immobilization stress) fully prevents stress-induced anxiety when administered into the lateral intermediate septum, confirming the role of septal CRFR2 in mediating stress-generated anxiety^[6].
Antisauvagine-30 (0.03-10 mg/kg; i.v. bolus), a selective CRF₂ receptor antagonist, completely blocks Urocortin 2-induced hypotension in conscious rats at doses of 1-10 mg/kg i.v., but has no effect on basal mean arterial blood pressure or heart rate when administered alone^[7].