PSFL2915 

PSFL2915 is a P2X receptor inhibitor with oral effectiveness, with an IC₅₀ of 0.319 μM for human P2X3, 0.261 μM for rat P2X2/3, and 13.3 μM for human P2X2, and exhibits ~42-fold selectivity for human P2X3 over human P2X2. PSFL2915 inhibits human P2X3 activation by preventing allosteric tightening of the inner pocket of the head domain required for channel opening, with magnesium-dependent inhibition. PSFL2915 inhibits rat P2X2/3 and human P2X2 receptor activation, and has low activity against human P2X1, P2X4, and P2X7 receptors. PSFL2915 can be used for the research of chronic cough^[1].

PSFL2915 (0.01-3 μM; 0.6 μM; 1 μM) is a noncompetitive, Mg²⁺-dependent allosteric inhibitor of hP2X3, with ~42-fold selectivity for hP2X3 over hP2X2, potent inhibition of rP2X2/3 heterotrimers, and low activity at other P2X subtypes^[1].
PSFL2915 (1 μM) exerts inhibitory effects by targeting the inner pocket of the head domain of hP2X3, as evidenced by potent inhibition of the hP2X4 chimera containing this hP2X3 domain^[1].
PSFL2915 (500 nM) prevents the ATP-induced conformational change of the inner pocket of the head domain in hP2X3, which is required for channel activation^[1].

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

PSFL2915 (15 mg/kg; oral gavage; twice daily; 7 days) produces significant cough-suppressant activity in male C57BL/6 mice with ammonia-induced chronic cough, with potency equivalent to Gefapixant (HY-101588) at the same dose^[1].
PSFL2915 (10 mg/kg; oral gavage; twice daily; 7 days) produces significant cough-suppressant activity in male Hartley guinea pigs with citric acid/ATP-induced chronic cough, with potency equivalent to Gefapixant (HY-101588) at the same dose^[1].
PSFL2915 (15 mg/kg; oral gavage; twice daily; 7-10 days) does not impair taste perception in male C57BL/6 mice, as measured by two-bottle preference tests for bitter and sweet tastants^[1].
PSFL2915 (10-20 mg/kg; intraperitoneal injection) does not impair bitter taste perception in male Sprague Dawley rats, as measured by two-bottle preference testing with quinine^[1].

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

462.36

C₁₅H₁₀O₁₃S₂

88134-39-8

O=C1C(O)=C(C2=CC(S(=O)(O)=O)=C(O)C(O)=C2)OC3=C(S(=O)(O)=O)C(O)=CC(O)=C31

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• [1]. Guo CR, et al. Chronic cough relief by allosteric modulation of P2X3 without taste disturbance. Nat Commun. 2023;14(1):5844. Published 2023 Sep 20.  [Content Brief]