PH-064 (tetra(hydrochloride))  (Synonyms: BIM-46187 tetrahydrochloride)

PH-064 tetrahydrochloride (BIM-46187 tetrahydrochloride) is an orally active inhibitor of the heterotrimeric G-protein complex. PH-064 tetrahydrochloride inhibits SERT activity and attenuates shear stress-induced Akt phosphorylation. PH-064 tetrahydrochloride has potent anti-hyperalgesia activity. PH-064 tetrahydrochloride inhibits G protein-coupled receptor-dependent tumorigenesis. PH-064 tetrahydrochloride can be used in the study of pain (e.g., inflammatory pain, neuropathic pain), GPCR-dependent tumors, and inflammatory lung injury^{[1][2][3][4][5][6]}.

PH-064 (20 μM；1 h) tetrahydrochloride 消除了 HCAEC 中由流动诱导的 Gαq/11 与 PECAM-1 的解离，并减弱了剪切应力诱导的 Akt 磷酸化^[2]。
PH-064 (10 μM-100 μM；30 min) tetrahydrochloride 浓度依赖性地抑制小鼠中脑和额叶皮质突触体中 SERT 介导的 5HT 摄取，并且还抑制了 TRex-SERT 细胞中的 SERT 活性^[3]。
PH-064 (对于基础 IP：即使在 10^-4 M 时) tetrahydrochloride 对 E151A-CCK2R 转染的 COS 细胞中基础 IP 生成没有抑制作用，但完全抑制了 Gastrin 刺激的 IP 生成 (EC₅₀：34 μM)^[5]。
PH-064 (10 μM；1 h) tetrahydrochloride 可将 RGS2 缺失的 BMDM 中的 IFNγ 生成降低至 WT-BMDM 的水平，且不影响 BMDM 活力^[6]。

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

PH-064 (0.1-1 mg/kg；静脉注射) tetrahydrochloride 在 Carrageenan (HY-125474) 诱发的痛觉过敏大鼠模型中表现出剂量依赖性的抗痛觉过敏作用，且不影响爪水肿和运动表现^[1]。
PH-064 (0.3-3 mg/kg；静脉注射) tetrahydrochloride 在慢性压迫性损伤 (CCI) 大鼠模型中表现出剂量依赖性的抗痛觉过敏作用^[1]。
PH-064 (75 mg/kg；口服；每日两次；16 天) tetrahydrochloride 在异种移植 E151A-CCK2R-NIH-3T3 细胞无胸腺裸鼠中表现出抗肿瘤活性，且无明显毒性^[5]。
PH-064 (3 mg/kg；静脉注射；在接受 LPS 治疗后 2 h) tetrahydrochloride 可使 RGS2 基因敲除小鼠肺中的 IFNγ 表达降低 80%，并促进肺水肿消退^[6]。

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

940.96

C₄₄H₆₂Cl₄N₈O₂S₂

2489449-03-6

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Favre-Guilmard C, et al. The novel inhibitor of the heterotrimeric G-protein complex, BIM-46187, elicits anti-hyperalgesic properties and synergizes with morphine. Eur J Pharmacol. 2008 Oct 10;594(1-3):70-6.  [Content Brief]

  [2]. Dela Paz NG, et al. Rapid flow-induced activation of Gαq/11 is independent of Piezo1 activation. Am J Physiol Cell Physiol. 2019 May 1;316(5):C741-C752.  [Content Brief]

  [3]. Haase J, et al. Sex and brain region-specific regulation of serotonin transporter activity in synaptosomes in guanine nucleotide-binding protein G(q) alpha knockout mice. J Neurochem. 2021 Oct;159(1):156-171.  [Content Brief]

  [4]. Auguet M, et al. SYNERGISTIC ANALGESIC INTERACTION BETWEEN MORPHINE AND BIM‐46187. European Journal of Pain, 2006, 10(S1): S89-S89.

  [5]. Silvente-Poirot S, et al. Heterotrimeric G-protein inhibitor BIM-46187 inhibits G-protein coupled receptor dependent tumorigenesis in athymic mice. Cancer Research, 2007, 67(9_Supplement): 5603-5603.

  [6]. Joshi JC, et al. RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury. iScience. 2025 Jan 27;28(2):111878.  [Content Brief]