XMD8-92 |
| Catalog No.GC11076 |
A selective ERK5 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1234480-50-2
Sample solution is provided at 25 µL, 10mM.
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IC50: XMD8-92 has been synthesized as a potent inhibitor of Mitogen-activated protein kinase 7 (MAPK7/BMK1; Kd = 80 nM). XMD8-92 blocks EGF-induced activation of BMK1 with IC50 of 240 nM [1].
The mitogen-activated protein kinases (MAPKs) are crucial components of signaling cascades that regulate numerous physiological processes. Four MAPK pathways have been identified thus far, including extracelluar-signal-regulated kinase 1/2 (ERK1/2), c-Jun-amino-terminal kinase (JNK), p38, and BMK1. XMD8-92 is a MAPKs kinase inhibitor with anti-cancer activity against lung and cervical cancers.
In vitro: In a previous study, XMD8-92 was shown to inhibit AsPC-1 cancer cell proliferation and tumor xenograft growth. In XMD8-92 treated tumors, significant downregulation of DCLK1was found and several of its downstream targets, including c-MYC, KRAS, NOTCH1, ZEB1, ZEB2, SNAIL, SLUG, OCT4, SOX2, NANOG, KLF4, LIN28, VEGFR1, and VEGFR2) via upregulation of tumor suppressor miRNAs, such as let-7a, miR-144, miR-200a-c, and miR-143/145. XMD8-92 was, however, not found to affect BMK1 downstream genes p21 and p53. These findings suggested that XMD8-92 treatment led to the inhibition of DCLK1 and downstream oncogenic pathways, which would be a promising chemotherapeutic agent against PDAC [2].
In vivo: In both immunocompetent and immunodeficient mice, XMD8-92 treatment was found to able to block the growth of lung and cervical xenograft tumors, respectively, by 95%. This remarkable anti-tumor effect of XMD8-92 in lung and cervical xenograft tumor models was due to its capacity to inhibit tumor cell proliferation through the PML suppressioninducted p21 checkpoint protein, as well as by blocking of the contribution of BMK1 in tumorassociated angiogenesis [3].
Clinical trial: XMD8-92 is still at preclinical development stage up to this point.
Reference:
[1] Yang Q, Lee JD. Targeting the BMK1 MAP kinase pathway in cancer therapy. Clin Cancer Res. 2011;17(11):3527-32.
[2] Sureban SM, May R, Weygant N, Qu D, Chandrakesan P, Bannerman-Menson E, Ali N, Pantazis P, Westphalen CB, Wang TC, Houchen CW. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014;351(1):151-61.
[3] Yang Q, Deng X, Lu B, Cameron M, Fearns C, Patricelli MP, et al. Pharmacological inhibition of
BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer Cell. 2010;18:258–67.
| Cell experiment [1]: | |
|
Cell lines |
Human pancreatic cancer AsPC-1 cell line |
|
Preparation method |
The solubility of this compound in DMSO is >23.8 mg/ml. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reacting condition |
10 and 15 μM for 48 h |
|
Applications |
Significant dose-dependent downregulation of DCLK1 mRNA and protein were observed following treatment with 10 and 15 μM of XMD8-92. Furthermore, a nearly 60% reduction in c-MYC, KRAS and NOTCH1 mRNA in AsPC-1 cells treated with XMD8-92 was also found. These data demonstrated that treatment AsPC-1 cells with XMD8-92 led to downregulation of DCLK1, c-MYC, KRAS and NOTCH1 mRNA. |
| Animal experiment [1]: | |
|
Animal models |
HeLa, A549 and LL/2 xenograft mouse model |
|
Dosage form |
50 mg/kg twice a day |
|
Application |
It was found that vehicle-treated tumors grew exponentially throughout the experiment, whereas treatment with XMD8-92 not only arrested the tumor growth but resulted in decrease in the tumor volume. Moreover, treatment with XMD8-92 resulted in a significant (>80%) reduction in tumor volume compared to control tumors. In addition, more than 2-fold decrease in the tumor weight following treatment with XMD8-92 was observed. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1] Sureban SM et al. XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism. Cancer Lett. 2014 Aug 28;351(1):151-61. |
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| Cas No. | 1234480-50-2 | SDF | |
| Chemical Name | 2-[2-ethoxy-4-(4-hydroxypiperidin-1-yl)anilino]-5,11-dimethylpyrimido[4,5-b][1,4]benzodiazepin-6-one | ||
| Canonical SMILES | CCOC1=C(C=CC(=C1)N2CCC(CC2)O)NC3=NC=C4C(=N3)N(C5=CC=CC=C5C(=O)N4C)C | ||
| Formula | C26H30N6O3 | M.Wt | 474.57 |
| Solubility | ≥ 23.75 mg/mL in DMSO | Storage | Store at 4°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1072 mL | 10.5359 mL | 21.0717 mL |
| 5 mM | 0.4214 mL | 2.1072 mL | 4.2143 mL |
| 10 mM | 0.2107 mL | 1.0536 mL | 2.1072 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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