A-1165442是有效，竞争性，有口服活性的 TRPV1 拮抗剂，对人TRPV1的 IC₅₀ 值为 9 nM。

A-1165442 is a potent, competitive and orally available TRPV1 antagonist with an IC 50 of 9 nM for human TRPV1.

Solid

IC50: 9 nM (human TRPV1)

A-1165442 displays potent, competitive antagonism at recombinant human TRPV1 activated by capsaicin (IC50=9 nM) and incomplete blockade of acid-evoked response (62% block at 30 μM). A-1165442 possesses excellent selectivity (>100-fold) versus other members of the TRP family (TRPA1, TRPM8, TRPV2, TRPV3) and other receptors expressed in peripheral sensory neurons including P2X2/3, Cav2.2, Nav channels, and KCNQ2/3. A-1165442 shows minimal cross-reactivity upon evaluation (10 μM) in a broad screening panel (n=74, CEREP) of cell-surface receptors, ion channels, and enzymes. has not independently confirmed the accuracy of these methods. They are for reference only.

A-1165442 exhibits excellent pharmacological selectivity, has a favorable pharmacokinetic profile, and demonstrates good efficacy against osteoarthritis pain in rodents. Oral administration of A-1165442 prevents capsaicin-induced nocifensive behaviors in rats, with an ED 50 of 9.5 μmol/kg corresponding to plasma concentration of 420 ng/mL (970 nM). A single dose of A-1165442 produces a robust effect on grip force, with an ED 50 of 35 μmol/kg measured 1 h postdosing. Repeated dosing of A-1165442 results in an increase in potency relative to acute analgesic efficacy. No significant changes in core body temperature is observed in conscious rats dosed with A-1165442 and this temperature-neutral profile is maintained in conscious dogs. has not independently confirmed the accuracy of these methods. They a

Room temperature in continental US; may vary elsewhere.

Powder -20°C 3 years；4°C 2 years

[1]. Voight EA, et al. Discovery of (R)-1-(7-chloro-2,2-bis(fluoromethyl)chroman-4-yl)-3-(3-methylisoquinolin-5-yl)urea (A-1165442): a temperature-neutral transient receptor potential vanilloid-1 (TRPV1) antagonist with analgesic efficacy. J Med Chem. 2014 Sep

In Vitro: DMSO : ≥ 100 mg/mL (231.56 mM)H₂O : < 0.1 mg/mL (insoluble)