A-1165442 is a potent, competitive and orally availableTRPV1antagonist with anIC₅₀of 9 nM for human TRPV1.

IC50: 9 nM (human TRPV1)^[1]

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^[1].

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 ED₅₀of 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 ED₅₀of 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^[1].

431.86

Solid

C₂₂H₂₀ClF₂N₃O₂

1221443-94-2

Room temperature in continental US; may vary elsewhere.

DMSO : ≥ 100 mg/mL(231.56 mM)

H₂O :< 0.1 mg/mL(insoluble)

*"≥" means soluble, but saturation unknown.

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

• 1.

  请依序添加每种溶剂： 10% DMSO    40%PEG300   5%Tween-80   45% saline

  Solubility: ≥ 2.5 mg/mL (5.79 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.79 mM，饱和度未知) 的澄清溶液。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

  将 0.9 g 氯化钠，完全溶解于 100 mL ddH2O 中，得到澄清透明的生理盐水溶液
• 2.

  请依序添加每种溶剂： 10% DMSO    90%corn oil

  Solubility: ≥ 2.5 mg/mL (5.79 mM); Clear solution

  此方案可获得 ≥ 2.5 mg/mL (5.79 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

  以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。