BIM-46174 

BIM-46174 is a heterotrimeric G protein complex inhibitor. BIM-46174 blocks GPCR downstream signaling by trapping Gα proteins in a nucleotide-free pocket conformation, thereby inhibiting Gαq-mediated calcium release, Gαs-mediated cAMP production, and GPCR-regulated cancer cell invasion. In vitro, BIM-46174 effectively suppresses a variety of clinically multidrug-resistant cell lines and induces tumor cell apoptosis through activation of caspase-3 and PARP cleavage. BIM-46174 also inhibits activation of the Neu1-MMP-9-GPCR signaling platform and downstream NF-κB signaling, and is widely used in the study of cancer signaling pathways and inflammation-related research, including lung cancer, pancreatic cancer, breast cancer, melanoma, and leukemia^[1][2][3][4].

BIM-46174 (1-100 μM; 1 h) in human breast cancer MCF-7 cells, as a heterotrimeric G protein inhibitor, significantly and reversibly blocks cAMP pathway activation mediated by cholera toxin or vasoactive intestinal peptide^[1].
BIM-46174 (5-30 μM; 1-24 h) selectively inhibits endothelin-1-coupled intracellular Ca²⁺ release in melanoma A2058 cells and markedly reverses or abolishes Wnt-2/3a- or neurotensin-induced invasive activity in colorectal cancer HCT8/S11, lung cancer LNM35, and colon cancer HT29 cells (IC₅₀ = 0.7 μM)^[1].
BIM-46174 (0.6-30 μM; 72-96 h) exhibits potent in vitro antiproliferative activity across a broad spectrum of human cancer cell lines, with IC₅₀ values ranging from 0.6 to 25 μM, effectively suppresses multiple clinical multidrug-resistant cell lines, and induces apoptosis via Caspase-3 activation and PARP cleavage^[1].
BIM-46174 (10-200 μM; 30 min-24 h) in macrophages (RAW-blue/RAW264.7) markedly blocks upstream G protein signaling, thereby inhibiting lmiquimod (HY-B0180)- or nucleic acid-induced TLR7/9 activation and MyD88 adaptor recruitment, resulting in suppression of NF-κB phosphorylation and pro-inflammatory cytokine (TNFα, MCP-1/CCL2) release^[2].
BIM-46174 (10-30 μM; 1-30 min) in 3T3-hEGFR cells and human pancreatic cancer cells (PANC-1/MiaPaCa-2) inhibits post-receptor Neu1 sialidase activation induced by epidermal growth factor (EGF) via blockade of upstream G protein signaling, thereby preventing downstream epidermal growth factor receptor (EGFR) autophosphorylation^[3].
BIM-46174 (100 μM; 2 h) in human embryonic kidney HEK293 cells strongly inhibits Gαq-dependent intracellular accumulation of the second messenger myo-inositol 1-phosphate (IP1) induced by Carbachol (HY-B1208)^[4].

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

BIM-46174 (20 or 25 mg/kg; i.p.; 25 mg/kg, twice daily for 14 days, or 20 mg/kg, twice daily for 5 days) shows limited antitumor activity as a single agent in a human SCC NCI-H69 xenograft model but significantly reduces tumor growth when combined with Cisplatin (HY-17394) or the farnesyltransferase inhibitor, with minimal toxicity^[1].
BIM-46174 (25 mg/kg; i.p.; twice daily for 8 days) in a human non-small cell lung cancer LNM35 xenograft model significantly reduces tumor growth when combined with Cisplatin (HY-17394) (1 mg/kg, once daily for 5 days) and exhibits good tolerability with low systemic toxicity^[1].
BIM-46174 (20 mg/kg; i.p.; twice daily for 5 days) in a human pancreatic cancer MIA PaCa-2 xenograft model significantly delays tumor growth and exhibits synergistic antitumor activity when combined with the topoisomerase inhibitor (HY-13622) while maintaining a favorable safety profile throughout the whole period^[1].
BIM-46174 (2 mg/kg/h; continuous intravenous infusion; 6 days) in a rat continuous infusion toxicity model is established as the highest tolerated dose before significant body weight loss, with no marked abnormalities in key biochemical parameters^[1].

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

398.56

C₂₂H₃₀N₄OS

195450-11-4

SC[C@H](N)C(N1CCN2C([C@@H]1CC3CCCCC3)=NC(C4=CC=CC=C4)=C2)=O

Room temperature in continental US; may vary elsewhere.

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

• [1]. Prévost GP, et al. Anticancer activity of BIM-46174, a new inhibitor of the heterotrimeric Galpha/Gbetagamma protein complex. Cancer Res. 2006 Sep 15;66(18):9227-34.

  [2]. Abdulkhalek S, et al. Neu1 sialidase and matrix metalloproteinase-9 cross-talk regulates nucleic acid-induced endosomal TOLL-like receptor-7 and -9 activation, cellular signaling and pro-inflammatory responses. Cell Signal. 2013 Nov;25(11):2093-105.

  [3]. Gilmour AM, et al. A novel epidermal growth factor receptor-signaling platform and its targeted translation in pancreatic cancer. Cell Signal. 2013 Dec;25(12):2587-603.

  [4]. Küppers J, et al. Tetrahydroimidazo[1,2-a]pyrazine Derivatives: Synthesis and Evaluation as Gαq -Protein Ligands. Chemistry. 2020 Oct 1;26(55):12615-12623.  [Content Brief]