SSR240612

SKU: orb1302140

Description

SSR240612 is a potent, orally bioavailable non-peptide antagonist that selectively targets the bradykinin B1 receptor, demonstrating high affinity (Ki = 0.48-0.73 nM) and excellent selectivity over the B2 receptor. It is a valuable research tool for investigating the role of the B1 receptor in pain, inflammation, and neuropathic conditions in both in vitro and in vivo models.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 464930-42-5
• MW: 793.41
• Purity: 98.95%
• Formula: C₄₂H₅₃ClN₄O₇S
• SMILES: Cl.COc1ccc2cc(ccc2c1)S(=O)(=O)N[C@H](CC(=O)N[C@H](Cc1ccc(CN2[C@@H](C)CCC[C@H]2C)cc1)C(=O)N(C)C(C)C)c1ccc2OCOc2c1
• Target: Bradykinin Receptor
• Solubility: H2O:Insoluble;10% DMSO+40% PEG300+5% Tween 80+45% Saline:4 mg/mL (5.04 mM);DMSO:100 mg/mL (126.04 mM)

Bioactivity

• Target IC50:
  Bradykinin B1 (human HEK-B1):0.73 nM (Ki)|Bradykinin B2 (human CHO-B2):358 nM (Ki)|Bradykinin B1 (human MRC5):0.48 nM (Ki)
• In Vivo:
  SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat . SSR240612 blocked tactile and cold allodynia at 3 h (ID(50)=5.5 and 7.1 mg/kg, respectively) in glucose-fed rats but had no effect in control rats. The antagonist (10 mg/kg) had no effect on plasma glucose and insulin, insulin resistance (HOMA index) and aortic superoxide anion production in glucose-fed rats .
• In Vitro:
  SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM . M. tuberculosis was not susceptible to the concentrations of antagonists tested, which suggests that the minimum inhibitory concentration values are larger than 250 μM for SSR240612 .
• Cell Research:
  [3H]Inositol phosphate1 accumulation was measured in MRC5 fibroblasts labeled with [3H]myoinositol according to the method described by Oury-Donat et al. Cells cultured in 6-well plates were labeled for 48 h with 5 μCi/ml [3H]myoinositol added to the culture medium (DMEM). Cells were then incubated for 4 h in DMEM containing 0.5 μg/ml IL-1β to induce B1 receptor synthesis. Agonist stimulation of inositol phosphate 1 accumulation was performed in DMEM containing 50 mM LiCl and test compounds. Antagonists were added 15 min before 10 nM Lys0-desArg10BK. After 30 min of incubation at 37°C, the medium was discarded, and the reaction was stopped by rapid addition of 1 ml of cold methanol and 1 N HCl (v/v). The cells were scraped, and the suspension was transferred to a glass tube with 1 ml of chloroform and 20 μl of 12 N HCl. The aqueous phase was neutralized by 350 μl of 1 M NaHCO3 and applied to 1 ml of Dowex AG1 × eight columns. [3H]inositol phosphate 1 was eluted with 0.2 M ammonium formate and 0.1 M formic acid. Radioactivity was measured by liquid scintillation spectrometry .
• Animal Research:
  Groups of eight male albino mice under isoflurane anesthesia received a 20-μl intraplantar injection into the right hind paw of 5 μg of IL-1β in phosphate-buffered saline/0.1% BSA. Forty minutes later (T = 0), mice received, under anesthesia, a 20-μl intraplantar injection in the same paw of des-Arg9-BK (10 μg/paw) in water. SSR240612 or vehicle [5% (v/v) ethanol and 5% (v/v) Tween 80 in water] was administered by oral route at the doses of 1, 3, and 10 mg/kg 1 h before des-Arg9-BK injection and by intraperitoneal route at the doses of 0.1, 0.3, and 1 mg/kg 40 min before des-Arg9-BK injection. Paw volume was measured with a plethysmometer at T =-2 h (initial measurement) and at several times after edema induction (T = 20, 40, 60, and 120 min). Paw edema volume was expressed in milliliters as the difference between the paw volume at each time after edema induction and the initial paw volume. Results for each group are expressed as mean ± S.E.M. of individual paw edema volumes .

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SSR 240612, SSR240612, SSR-240612, Inhibitor, inhibit, B1 Receptor, BradykininReceptor, Bradykinin Receptor

Compound Identifiers

PubChem CID

44235958