| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
BGB-102 targets the ErbB family of receptor tyrosine kinases, including EGFR (epidermal growth factor receptor), HER2 (human epidermal growth factor receptor 2), and HER4. These receptors play critical roles in cell proliferation, survival, differentiation, and migration. Overexpression or mutation of EGFR and HER2 is observed in various cancers and is associated with aggressive disease and poor prognosis. BGB-102 is a multi-kinase inhibitor that blocks the activity of these receptors, thereby inhibiting downstream signaling pathways such as PI3K/AKT and MAPK/ERK. The compound also acts as a kinase inhibitor against FLT3 and YES1 and as an antagonist against EGFR and VEGFR3.
|
|---|---|
| ln Vitro |
When JNJ-26483327 (5 µM or 10 µM) and Herceptin are administered together, SKBR3 cells' HER2 phosphorylation is decreased. After 3, 6, or 8 days of therapy, JNJ-26483327 had a stronger inhibitory effect on cell viability compared to Herceptin or JNJ-26483327 by itself. When compared to Herceptin alone and TAPI-1, JNJ-26483327 had a reduced inhibitory effect on cell survival in SKBR3 and BT474 cells [1].
BGB-102 demonstrates potent in vitro activity against EGFR, HER2, and HER4. The compound inhibits EGFR with an IC50 of 9.6 nM, HER2 with an IC50 of 18 nM, and HER4 with an IC50 of 40.3 nM. BGB-102 also acts against FLT3 and YES1 and as an antagonist against VEGFR3. By inhibiting these receptor tyrosine kinases, BGB-102 blocks downstream signaling pathways and suppresses tumor cell proliferation. The compound's multi-kinase inhibitory profile makes it a valuable tool for studying the roles of ErbB family kinases in cancer and for evaluating multi-targeted kinase inhibition as a therapeutic strategy. |
| ln Vivo |
In comparison to vehicle treatment, JNJ-26483327 (75 mg/kg, oral) delayed the growth of xenograft tumors; but, when combined with Herceptin, they removed the PKB feedback loop and were more successful in reducing the growth of xenograft tumors. possess a synergistic impact[1].
In vivo efficacy data for BGB-102 are not extensively documented in publicly available sources. Based on its potent inhibition of EGFR, HER2, and HER4, the compound is expected to have potential utility in cancer models driven by these receptors. BGB-102's multi-targeted approach may offer advantages over selective inhibitors by blocking multiple pathways simultaneously and potentially overcoming resistance mechanisms. The compound has been investigated for potential applications in macular degeneration and diseases related to genetic disorders and malformations. Further in vivo studies are needed to fully characterize the compound's therapeutic potential, including its efficacy in disease models, pharmacokinetic properties, and safety profile. |
| Enzyme Assay |
The in vitro enzyme inhibition assay for BGB-102 measures the inhibition of EGFR, HER2, and HER4 kinase activities. Recombinant human EGFR, HER2, or HER4 enzymes are incubated with varying concentrations of BGB-102 (typically ranging from nanomolar to micromolar) in the presence of ATP and a peptide substrate. The kinase reaction is allowed to proceed for a fixed period, and the extent of substrate phosphorylation is quantified using techniques such as fluorescence polarization, luminescence-based kinase assays, or radiometric measurement. IC50 values are determined by fitting dose-response curves to the inhibition data (9.6 nM for EGFR, 18 nM for HER2, 40.3 nM for HER4). The compound is dissolved in DMSO and diluted in assay buffer to achieve the desired final concentrations. Selectivity is assessed by testing the compound against a panel of other kinases, including FLT3, YES1, and VEGFR3. Appropriate positive controls and negative controls are included in each assay run.
|
| Cell Assay |
The in vitro cellular assay for BGB-102 is performed using cancer cell lines that are dependent on EGFR, HER2, or HER4 for proliferation, such as breast cancer cell lines (HER2-amplified) or NSCLC cell lines (EGFR-mutant). Cells are cultured in appropriate medium and treated with varying concentrations of BGB-102 or vehicle control (DMSO) for specified time points. Cell viability and proliferation are assessed using assays such as MTT, CellTiter-Glo, or by direct cell counting. The phosphorylation status of EGFR, HER2, HER4, and downstream signaling proteins (e.g., AKT, ERK) is assessed by Western blotting using phospho-specific antibodies. The compound's effects on cell cycle progression and apoptosis are evaluated by flow cytometry. Dose-response relationships are established by analyzing cell viability and signaling inhibition across different compound concentrations.
|
| Animal Protocol |
In vivo animal experiments with BGB-102 are not extensively described in publicly available sources. Based on its in vitro activity, potential in vivo studies would likely use immunocompromised mice bearing human tumor xenografts driven by EGFR, HER2, or HER4. Tumor cells would be implanted subcutaneously into the flank of nude or SCID mice. When tumors reach a predetermined size, animals would be randomized into treatment groups receiving BGB-102 or vehicle control. BGB-102 would be administered via oral gavage or intraperitoneal injection at various doses. Tumor volume would be measured twice weekly using calipers, and body weight monitored to assess tolerability. At study endpoint, tumors would be harvested for analysis of target engagement, downstream signaling, and markers of proliferation and apoptosis. The compound's antitumor efficacy would be evaluated by comparing tumor growth in treated versus control groups.
|
| ADME/Pharmacokinetics |
Detailed pharmacokinetic (PK) parameters for BGB-102 are not extensively documented in publicly available sources. The compound has a molecular weight of approximately 579.52 and a chemical formula of C31H31BrN4O3. BGB-102 is soluble in DMSO for formulation purposes. For in vivo administration, the compound would need to be formulated using appropriate vehicles to ensure adequate solubility and stability. The compound should be stored under conditions recommended by the manufacturer to maintain stability and prevent degradation. Detailed PK parameters including half-life, clearance, volume of distribution, and maximum concentration (Cmax) are not available from the current search results and would require consultation of the primary literature.
|
| Toxicity/Toxicokinetics |
Comprehensive toxicological data for BGB-102 are not extensively documented in publicly available sources. As a research-grade compound, BGB-102 is intended for laboratory research purposes only and is not approved for human therapeutic use. Standard laboratory safety practices should be followed when handling this compound, including the use of appropriate personal protective equipment and working in a well-ventilated area. The compound should be stored according to the manufacturer's recommendations to maintain stability and prevent degradation. Comprehensive toxicological profiling (e.g., LD50, maximum tolerated dose, organ-specific toxicity) is not available from the current search results and would require consultation of the primary literature or safety data sheets.
|
| References |
[1]. Gijsen M, et al. HER2 phosphorylation is maintained by a PKB negative feedback loop in response to anti-HER2 herceptin in breast cancer. PLoS Biol. 2010 Dec 21;8(12):e1000563
|
| Additional Infomation |
JNJ-26483327 is a small-molecule, multi-target, reversible tyrosine kinase inhibitor with high oral bioavailability and potential antitumor activity. JNJ-26483327 binds to and inhibits multiple members of the epidermal growth factor receptor (EGFR) family, including EGFR, HER2, and HER4; Src family kinases (Lyn, Yes, Fyn, Lck, and Src); and vascular endothelial growth factor receptor type 3 (VEGFR3). By inhibiting multiple signaling molecules that play key roles in various stages of tumorigenesis, this drug may inhibit tumor growth, invasion, migration, and metastasis. Furthermore, JNJ-26483327 can cross the blood-brain barrier (BBB).
BGB-102 is a research compound developed for studying the roles of ErbB family kinases (EGFR, HER2, HER4) in cancer and for evaluating multi-targeted kinase inhibition as a therapeutic strategy. The compound is also known as JNJ-26483327. BGB-102 is a potent multi-kinase inhibitor with IC50 values of 9.6 nM for EGFR, 18 nM for HER2, and 40.3 nM for HER4. The compound also acts as a kinase inhibitor against FLT3 and YES1 and as an antagonist against EGFR and VEGFR3. BGB-102 is not currently in clinical trials nor approved for therapeutic use; it remains an investigational tool compound for preclinical cancer research. BGB-102 is available from various chemical suppliers for research purposes. Its utility lies in its ability to inhibit multiple ErbB family kinases, enabling studies of their roles in cancer and other diseases. |
| Molecular Formula |
C22H25BRN4O2
|
|---|---|
| Molecular Weight |
457.363504171371
|
| Exact Mass |
456.116
|
| CAS # |
807640-87-5
|
| Related CAS # |
807640-87-5;1021686-80-5 (2HBr salt);
|
| PubChem CID |
11952856
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.7
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
6
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
29
|
| Complexity |
513
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
JXDYOSVKVSQGJM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C22H25BrN4O2/c1-27-8-4-3-5-9-29-21-11-17-19(12-20(21)28-2)24-14-25-22(17)26-18-10-16(23)7-6-15(18)13-27/h6-7,10-12,14H,3-5,8-9,13H2,1-2H3,(H,24,25,26)
|
| Chemical Name |
35-bromo-17-methoxy-5-methyl-11-oxa-2,5-diaza-1(4,6)-quinazolina-3(1,2)-benzenacycloundecaphane
|
| Synonyms |
JNJ26483327; BGB102; JNJ 26483327; BGB-102; JNJ-26483327; BGB 102.
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1865 mL | 10.9323 mL | 21.8646 mL | |
| 5 mM | 0.4373 mL | 2.1865 mL | 4.3729 mL | |
| 10 mM | 0.2186 mL | 1.0932 mL | 2.1865 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.
 Herceptin induces the activation of HER receptors and their dimerisation with HER2 as a result of an up-regulation and the release of HER ligands. |
|---|
 nhibiting PKB phosphorylation by a PKB inhibitor induces up-regulation of heregulin and ADAM17.PLoS Biol.2010 Dec 21;8(12):e1000563. |
 Combination of Herceptin with ADAM inhibitors decreases HER2 phosphorylation and is additive in cell viability inhibition.PLoS Biol.2010 Dec 21;8(12):e1000563. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA