| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg | |||
| 50mg | |||
| Other Sizes |
| Targets |
BIM-46187 targets heterotrimeric G-protein complexes, specifically silencing Gαq proteins by "freezing" Gαq in its empty pocket conformation, a conformational intermediate along the Gα activation pathway. By stabilizing this inactive conformation, BIM-46187 prevents Gαq from interacting with its downstream effectors, thereby inhibiting Gαq-mediated signaling. The compound also inhibits other G-protein-mediated signaling pathways, including cAMP generation (Gαs) and calcium release (Gαq). Its pan-G protein inhibitory activity makes it a valuable tool for studying G-protein signaling.
|
|---|---|
| ln Vitro |
In vitro, BIM-46187 is a novel, potent, and heterotrimeric pan G protein complex inhibitor. It specifically silences Gαq proteins by "freezing" Gαq in its empty pocket conformation. The compound inhibits heterotrimeric G-protein-mediated signaling, including cAMP generation (Gαs), calcium release (Gαq), and cancer cell invasion by Wnt-2 frizzled receptors. In cell-based assays, BIM-46187 treatment results in reduced G-protein-mediated signaling, leading to decreased cell proliferation and invasion. The compound's pan-G protein inhibitory activity makes it a valuable tool for studying G-protein signaling.
|
| ln Vivo |
In vivo, BIM-46187 has been studied for its potential in cancer therapy. As a pan-G protein inhibitor that silences Gαq signaling, the compound may have antitumor activity. Comprehensive in vivo efficacy studies are needed to fully characterize its therapeutic potential. BIM-46187 has been studied in preclinical settings for its effects on cancer cell invasion and tumor growth. Further studies are ongoing.
|
| Enzyme Assay |
In vitro receptor binding assays for BIM-46187 involve measuring its binding to heterotrimeric G-protein complexes. The assay typically uses purified G-protein complexes incubated with varying concentrations of BIM-46187. The compound's ability to stabilize the empty pocket conformation of Gαq is assessed using biophysical methods such as surface plasmon resonance (SPR) or isothermal titration calorimetry (ITC). These assays confirm the compound's mechanism of action.
|
| Cell Assay |
In vitro cell-based assays for BIM-46187 evaluate its effects on G-protein-mediated signaling. Cells expressing Gαq or other G-protein subunits are cultured and treated with BIM-46187. The compound's inhibition of G-protein signaling is assessed by measuring downstream effects such as calcium release (for Gαq), cAMP accumulation (for Gαs), or cell invasion (for Wnt-2 frizzled receptors). Cell viability and proliferation are assessed using MTT or other assays. These assays confirm the compound's functional activity.
|
| Animal Protocol |
In vivo animal experiments for BIM-46187 have been conducted in mouse models of cancer. Tumor-bearing mice are treated with BIM-46187 via various routes of administration. Tumor growth is monitored by caliper measurements, and tumor growth inhibition is calculated. The compound's effects on cancer cell invasion and metastasis are assessed. Pharmacokinetic studies are conducted to determine the compound's half-life, clearance, and tissue distribution. Comprehensive in vivo studies are ongoing.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for BIM-46187 are limited. The compound has a molecular weight of 795.11 g/mol and is soluble in DMSO. The compound's metabolic stability, half-life, and bioavailability have not been fully characterized. Comprehensive ADME studies are needed to fully characterize the pharmacokinetic profile of BIM-46187.
|
| Toxicity/Toxicokinetics |
The toxicity profile of BIM-46187 has not been extensively characterized. In laboratory settings, BIM-46187 should be handled as a hazardous chemical. Appropriate personal protective equipment should be used when handling the compound. The compound is for research use only and is not intended for human or veterinary use. Comprehensive toxicological studies are needed to fully characterize the safety profile of BIM-46187.
|
| References |
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.; Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer's amyloid precursor protein. FEBS J. 2017 Mar;284(5):742-753. doi: 10.1111/febs.14015. Epub 2017 Feb 10. PubMed PMID: 28102934.
|
| Additional Infomation |
BIM-46187 (PH-064) is a novel, potent, and heterotrimeric pan G protein complex inhibitor. It has a molecular formula of C₄₄H₅₈N₈O₂S₂ and a molecular weight of 795.11 g/mol. BIM-46187 specifically silences Gαq proteins by "freezing" Gαq in its empty pocket conformation. It inhibits heterotrimeric G-protein-mediated signaling, including cAMP generation, calcium release, and cancer cell invasion. BIM-46187 is a valuable tool for studying G-protein signaling.
|
| Molecular Formula |
C44H58N8O2S2
|
|---|---|
| Molecular Weight |
795.11372
|
| Exact Mass |
794.412
|
| CAS # |
892546-37-1
|
| PubChem CID |
11593027
|
| Appearance |
White to light yellow solid powder
|
| LogP |
9.133
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
56
|
| Complexity |
1160
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
C(C1CCCCC1)[C@@H]1N(C(=O)[C@@H](N)CSSC[C@H](N)C(N2CCN3C=C(C4C=CC=CC=4)N=C3[C@@H]2CC2CCCCC2)=O)CCN2C=C(C3C=CC=CC=3)N=C12
|
| InChi Key |
GGDNOAWICIHSAW-KEAHXZLPSA-N
|
| InChi Code |
InChI=1S/C44H58N8O2S2/c45-35(43(53)51-23-21-49-27-37(33-17-9-3-10-18-33)47-41(49)39(51)25-31-13-5-1-6-14-31)29-55-56-30-36(46)44(54)52-24-22-50-28-38(34-19-11-4-12-20-34)48-42(50)40(52)26-32-15-7-2-8-16-32/h3-4,9-12,17-20,27-28,31-32,35-36,39-40H,1-2,5-8,13-16,21-26,29-30,45-46H2/t35-,36-,39-,40-/m0/s1
|
| Chemical Name |
(2R,2'R)-3,3'-disulfanediylbis(2-amino-1-((S)-8-(cyclohexylmethyl)-2-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)propan-1-one)
|
| Synonyms |
PH-064 PH 064 PH064 BIM-46187 BIM 46187 BIM46187
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~125.77 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (3.14 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.2577 mL | 6.2884 mL | 12.5769 mL | |
| 5 mM | 0.2515 mL | 1.2577 mL | 2.5154 mL | |
| 10 mM | 0.1258 mL | 0.6288 mL | 1.2577 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
