| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
Purity: ≥98%
BAMB-4 (formerly known as ITPKA-IN-C14) is a novel and highly potent membrane-permeable inhibitor of inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) with IC50 of 37 uM in ADP-Glo Assay. Ectopic expression of the neuron-specific ITPKA in lung cancer cells increases their metastatic potential because the protein exhibits two actin regulating activities; it bundles actin filaments and regulates inositol-1,4,5-trisphosphate (InsP3)-mediated calcium signals by phosphorylating InsP3. Thus, in order to inhibit the metastasis-promoting activity of ITPKA, both its actin bundling and its InsP3kinase activity has to be blocked. BAMB-4 showed an inhibitory effect. Noteworthy, in kinase screens no targets of BAMB-4 were detected, indicating that the compound does not belong to the typical kinase inhibitors.
| Targets |
Inositol-1,4,5-trisphosphate-3-kinase A (ITPKA, InsP3 kinase activity), mixed type inhibitor [1]
|
||
|---|---|---|---|
| ln Vitro |
ITPKA is inhibited by BAMB-4 (0.3–40 μM), with an IC50 value of 37 μM[1]. InsP3 kinase activity is inhibited by BAMB-4 (40 μM) at an IC50 of 20 μM[1]. BAMB-4 has a high cellular uptake and high specificity at 100 μM over night[1]. Km is higher and V max is lower in BAMP-4 (0, 10, 20, and 40 μM) [1]. BAMP-4 (0–30 μM) is a mixed type inhibitor that affects both ATP and InsP3 binding. It affects the turnover of two substrates by binding to InsP3, which has a higher inhibition specificity[1].
1. InsP3 kinase activity inhibition: BAMB-4 (ITPKA-IN-C14) was identified as a potential inhibitor of ITPKA’s InsP3 kinase activity via high-throughput screening of 341,440 small molecules (0.7% hit rate, 237 potential inhibitors); it was selected among top three compounds (EPPC-3, BAMB-4, MEPTT-3) based on high specificity and hydrophobicity; further characterization confirmed it is a mixed type inhibitor of ITPKA’s InsP3 kinase activity [1] 2. Cellular uptake and stability: BAMB-4 (ITPKA-IN-C14) was nearly completely taken up by H1299 lung cancer cells, and remained stable after cellular uptake, exhibiting robust stability and high membrane permeability (superior to EPPC-3 and MEPTT-3) [1] 3. Metastasis-inhibiting potential: As ITPKA promotes lung cancer cell metastasis via actin bundling and InsP3-mediated calcium signal regulation, BAMB-4 (ITPKA-IN-C14) has the potential to partly inhibit the metastasis-promoting effect of ITPKA in lung tumor cells by blocking its InsP3 kinase activity [1] |
||
| ln Vivo |
|
||
| Enzyme Assay |
1. High-throughput screening for InsP3 kinase inhibition: A high-throughput screening assay was established to evaluate the inhibitory effect of 341,440 small molecules on the InsP3 kinase activity of ITPKA; compounds were incubated with recombinant ITPKA and its substrate InsP3 under optimized reaction conditions, and kinase activity was measured to identify potential inhibitors; hit compounds (237 in total) were further tested to determine IC₅₀ values, and compounds with high specificity and hydrophobicity (including BAMB-4 (ITPKA-IN-C14)) were selected for subsequent characterization [1]
2. Inhibitor type determination: Enzyme kinetic assays were performed to classify the inhibition type of BAMB-4 (ITPKA-IN-C14); reaction rates were measured at varying concentrations of InsP3 (substrate) and BAMB-4 (ITPKA-IN-C14), and Lineweaver-Burk plots were generated to analyze the kinetic parameters, confirming that BAMB-4 (ITPKA-IN-C14) acts as a mixed type inhibitor of ITPKA’s InsP3 kinase activity [1] |
||
| Cell Assay |
1. Cellular uptake and stability assay (H1299 cells): H1299 lung cancer cells were cultured in appropriate medium and incubated with BAMB-4 (ITPKA-IN-C14) (along with EPPC-3 and MEPTT-3 as controls) under standard cell culture conditions; after incubation, cells were harvested, and the intracellular concentration of BAMB-4 (ITPKA-IN-C14) was quantified at different time points to evaluate cellular uptake efficiency; the stability of BAMB-4 (ITPKA-IN-C14) inside cells was assessed by measuring its concentration over an extended incubation period, confirming its nearly complete uptake and robust intracellular stability [1]
|
||
| Animal Protocol |
|
||
| ADME/Pharmacokinetics |
1. Membrane permeability: BAMB-4 (ITPKA-IN-C14) has high membrane permeability, and H1299 cells almost completely take up the compound (superior to EPPC-3 and MEPTT-3) [1] 2. Intracellular stability: BAMB-4 (ITPKA-IN-C14) remains stable after being taken up by H1299 cells, and no significant degradation was observed [1]
|
||
| References | |||
| Additional Infomation |
1. Background: Ectopic expression of neuron-specific ITPKA in lung cancer cells can increase metastatic potential through two actin-regulated activities: one is binding actin filaments, and the other is regulating InsP3-mediated calcium signaling (through InsP3 phosphorylation); inhibiting the metastasis-promoting effect of ITPKA requires blocking both of its activities simultaneously, and BAMB-4 (ITPKA-IN-C14) targets the InsP3 kinase activity of ITPKA [1] 2. Mechanism of action: BAMB-4 (ITPKA-IN-C14) is a hybrid ITPKA InsP3 kinase activity inhibitor. Its high membrane permeability allows it to enter lung cancer cells and inhibit enzyme activity, thereby partially blocking the metastasis-promoting effect of ITPKA [1] 3. Therapeutic potential: BAMB-4 (ITPKA-IN-C14) is the first highly membrane-permeable ITPKA discovered to date. Inhibitors of InsP3 kinase activity provide a tool compound for studying ITPKA-mediated lung cancer metastasis and are expected to become lead compounds for the development of anti-metastatic drugs. [1]
|
| Molecular Formula |
C15H12N2O2
|
|
|---|---|---|
| Molecular Weight |
252.27
|
|
| Exact Mass |
252.09
|
|
| CAS # |
891025-25-5
|
|
| Related CAS # |
|
|
| PubChem CID |
8087347
|
|
| Appearance |
White to off-white solid powder
|
|
| LogP |
3.461
|
|
| Hydrogen Bond Donor Count |
1
|
|
| Hydrogen Bond Acceptor Count |
3
|
|
| Rotatable Bond Count |
2
|
|
| Heavy Atom Count |
19
|
|
| Complexity |
326
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
IEPCQLHHUYRTEY-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C15H12N2O2/c1-10-6-8-11(9-7-10)15(18)16-14-12-4-2-3-5-13(12)19-17-14/h2-9H,1H3,(H,16,17,18)
|
|
| Chemical Name |
N-(1,2-benzoxazol-3-yl)-4-methylbenzamide
|
|
| Synonyms |
|
|
| 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) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (9.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.9640 mL | 19.8200 mL | 39.6401 mL | |
| 5 mM | 0.7928 mL | 3.9640 mL | 7.9280 mL | |
| 10 mM | 0.3964 mL | 1.9820 mL | 3.9640 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
COA