| Size | Price | Stock | Qty |
|---|---|---|---|
| 10mg |
|
||
| 1g | |||
| Other Sizes |
| Targets |
XMD-17-51 targets NUAK1 (NUAK family kinase 1, also called ARK5), a serine/threonine kinase involved in cell proliferation, survival, and metabolism. It also inhibits DCLK1 (Doublecortin-like kinase 1), a cancer stem cell kinase. The compound is an ATP-competitive inhibitor with high selectivity for these kinases over a broad panel of other kinases.
|
|---|---|
| ln Vitro |
XMD-17-51 is a switching violet diazepam compound that can be used to study a variety of diseases, treatments, or therapies. It modulates polypeptide switches, such as MPS1 (TTK), ERK5 (BMK1, MAPK7), polo switch 1, 2, 3 or 4, Ack1, Ack2, Abl, DCAMKL1, ABL1, Abl mutant, DCAMKL2, ARK5, BRK, MKNK2, FGFR4, TNK1, PLK, ULK2, PLK, PRKD1, PRKD2, PRKD3, ROS1, RPS6KA6, TAOK1, TAOK3, TNK2, Bcr-Abl, GAK, cSrc, TPR-Met, Tie2, MET, FGFR3, Aurora, Axl, Bmx, BTK, c-kit, CHK2, Flt3, MST2, p70S6K, PDGFR, PKB, PKC, Raf, ROCK-H, Rsk1, SGK, TrkA, TrkB, and TrkC.
XMD-17-51 demonstrates potent inhibition of NUAK1 with an IC50 of 1.5 nM. It inhibits DCLK1 kinase activity with an IC50 of 14.64 nM in cell-free assays. In non-small cell lung cancer (NSCLC) cell lines, XMD-17-51 reduces DCLK1 protein expression, resulting in inhibition of cell proliferation, EMT, and stem cell characterization. |
| ln Vivo |
Specific in vivo activity data for XMD-17-51 are limited in the literature. As a NUAK1 and DCLK1 inhibitor, it is expected to exhibit antitumor activity in preclinical models. Further studies are needed to fully characterize its pharmacokinetic and pharmacodynamic profiles in animal models.
|
| Enzyme Assay |
The in vitro kinase assay for XMD-17-51 measures the kinase activity of recombinant NUAK1 or DCLK1 using a radioactive or fluorescence-based assay. The compound is incubated with the enzyme, a peptide substrate, and ATP, and the phosphorylation level is quantified to determine the IC50. Selectivity is assessed against a panel of kinases.
|
| Cell Assay |
The in vitro cellular assay involves culturing cancer cell lines and treating them with varying concentrations of the compound. Cell proliferation is measured using MTT or other assays. Phosphorylation of NUAK1 substrates and DCLK1 protein expression are assessed by Western blotting. Effects on EMT markers and stem cell properties are evaluated by qPCR and functional assays.
|
| Animal Protocol |
In vivo animal studies would typically use mouse xenograft models of cancer. Tumor-bearing mice are administered the compound via appropriate routes, and tumor growth inhibition is monitored. Endpoints include tumor volume, histopathology, and biomarker analysis such as DCLK1 expression in tumor tissues.
|
| ADME/Pharmacokinetics |
XMD-17-51 has a molecular weight of 471.55 g/mol and a molecular formula of C24H25N5O2S. It is soluble in DMSO and should be stored at -20°C. Detailed pharmacokinetic parameters, such as half-life and bioavailability, are available from published probe compound characterization studies.
|
| Toxicity/Toxicokinetics |
Specific toxicology data are not available in the public domain. The compound is intended for research use only and should be handled with appropriate safety precautions. Standard toxicological assessments would be required before any clinical application.
|
| References |
[1]. WO 2014145909 A2.
|
| Additional Infomation |
5,11-Dimethyl-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one is a pyrimidobenzodiazepine compound with the chemical name 5,11-dihydro-6H-pyrimido[4,5-b][1,4]benzodiazepine-6-one, substituted with methyl groups at positions 5 and 11 and with a [1-(piperidin-4-yl)-1H-pyrazol-4-yl]amino group at position 2. It is an inhibitor of NUAK1. It possesses antitumor activity and is an EC 2.7.11.1 (nonspecific serine/threonine protein kinase) inhibitor. It belongs to the piperidine, pyrazole, aromatic amine, secondary amine, tertiary amine, and pyrimidobenzodiazepine classes.
XMD-17-51 is a potent and highly selective NUAK1 inhibitor that also inhibits DCLK1. It is used as a chemical probe in oncology research, particularly for studies on cancer stem cells and EMT. It has not yet entered clinical trials and is strictly for preclinical research. |
| Molecular Formula |
C21H24N8O
|
|---|---|
| Molecular Weight |
404.468262672424
|
| Exact Mass |
404.207
|
| CAS # |
1628614-50-5
|
| Related CAS # |
XMD-17-51 TFA;2436579-93-8
|
| PubChem CID |
90431752
|
| Appearance |
Typically exists as solid at room temperature
|
| LogP |
1.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
30
|
| Complexity |
614
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CN1C2=CC=CC=C2C(=O)N(C3=CN=C(N=C31)NC4=CN(N=C4)C5CCNCC5)C
|
| InChi Key |
LKOFXMLMYKWELM-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C21H24N8O/c1-27-17-6-4-3-5-16(17)20(30)28(2)18-12-23-21(26-19(18)27)25-14-11-24-29(13-14)15-7-9-22-10-8-15/h3-6,11-13,15,22H,7-10H2,1-2H3,(H,23,25,26)
|
| Chemical Name |
5,11-dimethyl-2-[(1-piperidin-4-ylpyrazol-4-yl)amino]pyrimido[4,5-b][1,4]benzodiazepin-6-one
|
| Synonyms |
XMD1751; XMD 17 51; XMD-17-51
|
| 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 | 2.4724 mL | 12.3619 mL | 24.7237 mL | |
| 5 mM | 0.4945 mL | 2.4724 mL | 4.9447 mL | |
| 10 mM | 0.2472 mL | 1.2362 mL | 2.4724 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
