| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg | |||
| 500mg | |||
| Other Sizes |
Purity: ≥98%
MBQ-167 (MBQ167) is a dual inhibitor of Rac/Cdc42 (Ras-related C3 botulinum toxin substrate and cell division control protein 42 homolog) with anticancer activity. In metastatic MDA-MB-231 cells, it inhibits Rac 1/2/3 and Cdc42 with IC50 values of 103 nM and 78 nM, respectively. Thus, without influencing the activities of Rho, MAPK, or Akt, MBQ-167 dramatically reduces the downstream effector p21-activated kinase (PAK) signaling and the activity of STAT3. Additionally, MBQ-167 prevents the migration, viability, and formation of mammospheres in breast cancer cells. Additionally, MBQ-167 inhibits actin-based extensions on the cell surface and causes a loss of cell polarity in cancer cells that have undergone the epithelial-to-mesenchymal transition, which ultimately leads to the cells' separation from the substratum. Extended (120 h) incubation in MBQ-167 reduces the viability of metastatic cancer cells with a GI50 of about 130 nmol/L, while having no effect on mammary epithelial cells that are not cancerous. Cancer cell viability is lost as a result of G2-M cell-cycle arrest mediated by MBQ-167 and subsequent apoptosis, particularly of the detached cells. In immunocompromised mice, MBQ-167 inhibits the growth and metastasis of mammary tumors by about 90% in vivo. Finally, MBQ-167 has the potential to be developed as an anticancer medication and a dual inhibitory probe for the study of Rac and Cdc42 because it is 10× more potent than other Rac/Cdc42 inhibitors that are currently on the market.
| Targets |
Cdc42 ( IC50 = 78 nM ); Ras 1/2/3 ( IC50 = 103 nM )
In vitro activity: MBQ-167 (≥100 nM) causes a loss of polarity in metastatic breast cancer cells. Approximately 95% of metastatic MDA-MB-231 cells round and detach from the substratum after being treated with 500 nM MBQ-167 for 24 hours. AGS and NCI-N87 gastric cancer cells, SH-SY5Y neuroblastoma cells, Mia-PaCa-2 pancreatic cancer cells, SKOV3 ovarian cancer cells, GFP-HER2-BM, MDA-MB-468, and Hs578t human breast cancer cells are among the mesenchymal cancer cell types in which MBQ-167 induces this phenotype. After being treated for 24 hours with 250 nM MBQ-167, the attached population of MDA-MB-231 cells shows a decrease in Rac activation of about 25%, whereas the detached cells show a more responsive decrease of about 75%. Treatment with 250 or 500 nM MBQ-167 at earlier times (6 h) causes the attached cell population to exhibit a 40–50% reduction in Rac activity, whereas the detached population shows a similar inhibition[1]. |
|---|---|
| ln Vitro |
In vitro activity: MBQ-167 (≥100 nM) causes a loss of polarity in metastatic breast cancer cells. Approximately 95% of metastatic MDA-MB-231 cells round and detach from the substratum after being treated with 500 nM MBQ-167 for 24 hours. AGS and NCI-N87 gastric cancer cells, SH-SY5Y neuroblastoma cells, Mia-PaCa-2 pancreatic cancer cells, SKOV3 ovarian cancer cells, GFP-HER2-BM, MDA-MB-468, and Hs578t human breast cancer cells are among the mesenchymal cancer cell types in which MBQ-167 induces this phenotype. After being treated for 24 hours with 250 nM MBQ-167, the attached population of MDA-MB-231 cells shows a decrease in Rac activation of about 25%, whereas the detached cells show a more responsive decrease of about 75%. Treatment with 250 or 500 nM MBQ-167 at earlier times (6 h) causes the attached cell population to exhibit a 40–50% reduction in Rac activity, whereas the detached population shows a similar inhibition[1].
JANEX-1 treatment inhibited the autophagy flux induced by IL4 in murine splenic B cells, as measured by the accumulation of LC3B-II protein via immunoblotting. [4] JANEX-1 treatment also inhibited IL4-induced autophagy flux in human primary B cells isolated from peripheral blood. [4] Treatment with JANEX-1 inhibited the IL4-promoted binding of BECN1 to ATG14, PIK3R4, and PIK3C3 components of the autophagy-specific PtdIns3K complex in murine primary B cells, as shown by co-immunoprecipitation assays. [4] |
| ln Vivo |
MBQ-167-treated mice show a statistically significant decrease in tumor growth. Around 80% of tumor growth is reduced at sacrifice by 1.0 mg/kg BW of MBQ-167, and approximately 95% of tumor growth is reduced by 10 mg/kg BW of MBQ-167 treatment. MBQ-167 is 10X more effective than EHop-016 because it only reduces tumor growth by about 40% at 10 mg/kg BW. Mice treated with MBQ-167 exhibit comparable doubling times for both treatments (10 and 11 days)[1].
In an ovalbumin (OVAL)-sensitized murine asthma model, intraperitoneal administration of JANEX-1 reduced the enhanced autophagy flux observed in pulmonary B cells isolated from asthma-prone mice. This indicates that JANEX-1 can inhibit Th2 cytokine-induced B cell autophagy in the context of allergic asthma in vivo. [4] |
| Enzyme Assay |
In metastatic MDA-MB-231 cells, MBQ-167 is a dual inhibitor of Rac/Cdc42 (Ras-related C3 botulinum toxin substrate and cell division control protein 42 homolog), with IC50 values of 103 nM for Rac 1/2/3 and 78 nM for Cdc42, respectively.
(The literature does not describe detailed enzymatic or binding assays (e.g., kinase activity, SPR, ITC) specifically performed with JANEX-1 to determine its potency against JAK3 or other targets.)[4] |
| Cell Assay |
MBQ-167 at 250 or 500 nM is applied to MDA-MB-231 cells for a 24-hour period. To see the F-actin and the focal adhesions, cells are permeabilized, fixed, and stained with either vinculin or p-tyrosine.
For assessing the role of JAK signaling in IL4-induced autophagy, murine splenic B cells were treated with IL4 in the presence or absence of the JAK3 inhibitor JANEX-1. After treatment, cells were lysed, and the accumulation of LC3B-II protein was analyzed by immunoblotting to measure autophagy flux. [4] Human primary B cells isolated from peripheral blood were treated with human IL4 (HsIL4) in the presence or absence of JANEX-1. Autophagy flux was subsequently assessed by immunoblotting for LC3B-II accumulation. [4] To investigate the mechanism of IL4-induced autophagy, murine splenic B cells were treated with IL4 with or without JANEX-1 pre-treatment. Cell lysates were then subjected to co-immunoprecipitation using an anti-BECN1 antibody, followed by immunoblotting for components of the PtdIns3K complex (PIK3C3, ATG14, PIK3R4). [4] |
| Animal Protocol |
Mice: We utilize 4- to 5-week-old female athymic nu/nu mice. The fourth right mammary fat pad is injected with GFP-HER2-BM cells (~5×105) in Matrigel under isofluorane inhalation to create orthotopic primary tumors. Animals are randomized into treatment groups (n=6) one week after vaccination, following tumor establishment. Three times a week, mice are given either 1. or 10 mg/kg BW MBQ-167 via intraperitoneal injection in a 100 μL volume, or a vehicle solution (12.5% ethanol, 12.5% Cremophor, and 75% 1X PBS pH 7.4). Until day 65, when sacrifice occurs, treatments are continued[1]. In the OVAL-sensitized asthma model, wild-type asthma-prone mice were injected intraperitoneally with JANEX-1 (dissolved in phosphate-buffered saline, PBS) at a dose of 50 µg per gram of body weight per day. The injections were administered on days 19 to 23 of the protocol. This treatment was performed prior to and during the airway challenge phase (days 21-23) with atomized OVAL. On day 24, mice were sacrificed, and lung tissues were collected for isolation of pulmonary B cells and subsequent assessment of autophagy flux. [4] |
| References | |
| Additional Infomation |
MBQ-167, a Rac/Cdc42 inhibitor, is an orally bioavailable Rho GTPase inhibitor that inhibits Ras-associated C3 botulinum toxin substrate (Rac) and cell division control protein 42 homolog (Cdc42), exhibiting potential antitumor activity. After oral administration, MBQ-167 targets and binds to the GTP-binding proteins Rac and Cdc42 expressed on certain cancer cells and immunosuppressive immune cells in the tumor microenvironment (TME), inhibiting their activity. This inhibits the p21-activated kinase (PAK) and signal transduction and activating transcription factor 3 (STAT3) signaling pathways, inducing cell cycle arrest and apoptosis, and inhibiting cancer cell proliferation and migration. MBQ-167 also reduces tumor-infiltrating macrophages and myeloid-derived suppressor cells (MDSCs) in the TME, potentially eliminating the immunosuppressive properties of the TME. Rac and Cdc42 are homologous small GTPases that are overexpressed or overactivated in various cancers. They regulate epithelial-mesenchymal transition, cell migration, invasion, cell cycle progression, and metastasis. In this study, JANEX-1 was used as a pharmacological tool to inhibit the JAK3 signaling pathway. The results showed that IL4-induced B cell autophagy depends on the JAK (JAK1/3) signaling pathway, and that inhibiting this pathway with JANEX-1 attenuated B cell autophagy in vitro and in vivo. This finding helps to understand the role of the IL4-JAK signaling axis in regulating B cell function in the pathogenesis of allergic asthma. [4]
|
| Molecular Formula |
C22H18N4
|
|
|---|---|---|
| Molecular Weight |
338.405124187469
|
|
| Exact Mass |
338.15
|
|
| Elemental Analysis |
C, 78.08; H, 5.36; N, 16.56
|
|
| CAS # |
2097938-73-1
|
|
| Related CAS # |
|
|
| PubChem CID |
129896932
|
|
| Appearance |
Light yellow to yellow solid powder
|
|
| LogP |
4.7
|
|
| Hydrogen Bond Donor Count |
0
|
|
| Hydrogen Bond Acceptor Count |
2
|
|
| Rotatable Bond Count |
3
|
|
| Heavy Atom Count |
26
|
|
| Complexity |
477
|
|
| Defined Atom Stereocenter Count |
0
|
|
| InChi Key |
LJCANTASZGYJLG-UHFFFAOYSA-N
|
|
| InChi Code |
InChI=1S/C22H18N4/c1-2-25-20-11-7-6-10-18(20)19-14-17(12-13-21(19)25)26-22(15-23-24-26)16-8-4-3-5-9-16/h3-15H,2H2,1H3
|
|
| Chemical Name |
9-ethyl-3-(5-phenyltriazol-1-yl)carbazole
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.03.00
|
|
| 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 (7.39 mM) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9550 mL | 14.7750 mL | 29.5500 mL | |
| 5 mM | 0.5910 mL | 2.9550 mL | 5.9100 mL | |
| 10 mM | 0.2955 mL | 1.4775 mL | 2.9550 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT06075810 | Recruiting | Drug: MBQ-167 | Breast Cancer Breast Neoplasm Breast Cancer Stage IV |
MBQ Pharma | November 9, 2023 | Phase 1 |
Breast cancer cell phenotype following MBQ-167 treatment.
Inhibitory effect of MBQ-167 on Rac and Cdc42 activation.Mol Cancer Ther.2017 May;16(5):805-818. |
|---|
The effect of MBQ-167 on signaling downstream of Rac and Cdc42.Mol Cancer Ther.2017 May;16(5):805-818. |
Effect of MBQ-167 on cell survival.
In-vivoefficacy of MBQ-167 compared with EHop-016.Mol Cancer Ther.2017 May;16(5):805-818. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
