K41498 TFA 

K41498 TFA is a highly selective CRF 2 receptor antagonist, with a K_i of 0.66 nM for human CRF2α receptor and a K_i of 0.62 nM for human CRF2β receptor. K41498 TFA inhibits cAMP accumulation in cells expressing CRF2. K41498 TFA antagonizes the hypotensive response induced by systemic administration of urocortin in conscious rats. K41498 TFA undergoes radioiodination without loss of activity and serves for autoradiographic studies of native CRF2 receptors in rat brain and peripheral tissues^[2].

K41498 (incubated at 22°C for 120 min) TFA exhibits highly selective and high-affinity binding to hCRF₂α and hCRF₂β receptors in membrane homogenates of stably transfected HEK293 cells (K_i = 0.66 nM and 0.62 nM, respectively), which is significantly superior to its binding to hCRF₁ receptor^[1].
K41498 (10 μM in hCRF₁-expressing cells; 100 nM in hCRF₂α- and hCRF₂β-expressing cells; treated at 37°C for 10 min) TFA is a potent, selective antagonist that inhibits cAMP accumulation in Svg-stimulated HEK293 cells expressing hCRF₂α and hCRF₂β. It exhibits only extremely low intrinsic agonist activity across all three receptor subtypes and shows weak activity at the hCRF₁ receptor^[1].
K41498 (100 nM, 10 min at 37°C for CRF₂α/CRF₂β cells; 10 μM, 10 min at 37°C for CRF₁ cells) TFA potently inhibits sauvagine-induced cAMP accumulation in HEK293 cells expressing human CRF₂α and human CRF₂β at a concentration of 100 nM, shows only weak inhibitory effect on HEK293 cells expressing human CRF₁ at a concentration of 10 μM, and exhibits only extremely low intrinsic agonist activity in all three of the above-mentioned cell lines^[2].

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

K41498 (1 mg/kg; i.v.; single administration) TFA specifically reduces the uptake of ¹²³I-K31440 in the small intestine of mice by 35%, confirming that it binds to peripheral CRF₂ receptors^[1].
K41498 (1.84 mg; i.v.; single administration, 10 minutes prior to urocortin administration) TFA completely blocks the systemic urocortin-induced hypotensive response in conscious male Wistar-Kyoto rats, whereas K41498 (2.35 mg; i.c.v.; single administration, 10 minutes prior to urocortin administration) fails to block the pressor effect induced by urocortin^[2].

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

3632.20 (free base)

C₁₆₂H₂₇₆N₄₈O₄₆.xC₂HF₃O₂

Solid

White to off-white

{D-Phe}-His-Leu-Leu-Arg-Lys-{Nle}-Ile-Glu-Ile-Glu-Lys-Gln-Glu-Lys-Glu-Lys-Gln-Gln-Ala-Ala-Asn-Asn-Arg-Leu-Leu-Leu-Asp-Thr-Ile-NH2

{D-Phe}-HLLRK-{Nle}-IEIEKQEKEKQQAANNRLLLDTI-NH2

Room temperature in continental US; may vary elsewhere.

Sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. A Rühmann, et al. Design, synthesis and pharmacological characterization of new highly selective CRF(2) antagonists: development of 123I-K31440 as a potential SPECT ligand. Peptides. 2002 Mar;23(3):453-60.  [Content Brief]

  [2]. A J Lawrence, et al. The highly selective CRF(2) receptor antagonist K41498 binds to presynaptic CRF(2) receptors in rat brain. Br J Pharmacol  [Content Brief]