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 abrogates the flow-induced dissociation of Gαq/11 from PECAM-1 in HCAECs and attenuates shear stress-induced Akt phosphorylation^[2].
PH-064 (10 μM-100 μM; 30 min) tetrahydrochloride concentration-dependently inhibits SERT-mediated 5HT uptake in mouse midbrain and frontal cortex synaptosomes, and also inhibits SERT activity in TRex-SERT cells^[3].
PH-064 (for basal IP: even at 10^-4 M) tetrahydrochloride has no inhibitory effect on basal IP production in E151A-CCK2R-transfected COS cells, but completely inhibits Gastrin-stimulated IP production (EC₅₀: 34 μM)^[5].
PH-064 (10 μM; 1 h) tetrahydrochloride reduces IFNγ generation in RGS2 null BMDMs to the level of WT-BMDMs without affecting BMDM viability^[6].

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

PH-064 (0.1-1 mg/kg; i.v.) tetrahydrochloride elicits dose-dependent anti-hyperalgesic effect in Carrageenan (HY-125474)-induced hyperalgesia model in rats, without affecting paw oedema and motor performance^[1].
PH-064 (0.3-3 mg/kg; i.v.) tetrahydrochloride shows dose-dependent anti-hyperalgesic effect in chronic constriction injury (CCI) model in rats^[1].
PH-064 (75 mg/kg; p.o.; twice a day; 16 days) tetrahydrochloride exhibits antitumor activity in athymic nude mouse xenografts with E151A-CCK2R-NIH-3T3 cells without apparent toxicity^[5].
PH-064 (3 mg/kg; i.v.; 2 h after i.t. LPS) tetrahydrochloride reduces IFNγ expression by 80% in RGS2 null mouse lungs and promotes resolution of lung edema^[6].

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

940.96

C₄₄H₆₂Cl₄N₈O₂S₂

2489449-03-6

O=C([C@H](CSSC[C@@H](C(N1CCN2C([C@@H]1CC3CCCCC3)=NC(C4=CC=CC=C4)=C2)=O)N)N)N([C@H]5CC6CCCCC6)CCN(C5=N7)C=C7C8=CC=CC=C8.Cl.Cl.Cl.Cl

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]