| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Neurofibrillary tangles (NFTs) (Ki = 0.36 nM for binding to NFTs in human AD brain homogenates using [3H]8 as radioligand; Kd = 0.42 nM for [3H]6 in saturation binding studies) [1]
β-amyloid (Ki > 10000 nM for binding to β-amyloid using [3H]7 as radioligand in human AD brain homogenates) [1] MK-6240 targets neurofibrillary tangles (NFTs), which are aggregates of hyperphosphorylated tau protein found in the brains of patients with Alzheimer's disease and other tauopathies. It binds to NFTs with high specificity and selectivity. The compound is a PET tracer, and its binding can be visualized and quantified using PET imaging to assess tau pathology in the brain. |
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| ln Vitro |
MK-6240 (CAS#: 1841078-87-2) in vitro: In competition binding assays using human Alzheimer's disease (AD) cortex homogenates, compound 6 (non-radiolabeled MK-6240) exhibited a Ki of 0.36 nM for binding to neurofibrillary tangles (NFTs) with [3H]8 as the radioligand, and showed high selectivity over β-amyloid with Ki > 10000 nM using [3H]7. [1]
Saturation binding studies with [3H]6 in NFT-rich AD cortex homogenates revealed high-affinity saturable binding to NFTs with Kd = 0.42 nM and Bmax/Kd ratio of approximately 211. When using compound 2 (a structurally distinct selective NFT ligand) as blocking agent, a similar Bmax/Kd ratio (~238) was observed, indicating minimal off-target binding. No specific binding was detected in non-AD cortex homogenates. [1] Autoradiographic imaging on human AD brain slices showed that [3H]6 produced strong displaceable binding in grey matter (regions with high NFT load) by self-block or block with compound 2, matching PHF6 immunostaining for NFTs. [1] Compound 6 was not a substrate for human or rat P-glycoprotein (P-gp) mediated efflux (BA:AB ratio ~1.3 at 0.1 μM) in LLC-PK1 cells expressing P-gp, and showed high passive permeability in control LLC-PK1 cells (Papp > 29 × 10⁻⁶ cm·s⁻¹). [1] Evaluation of compound 6 in a counter-screen panel of 118 receptor and enzyme targets revealed no ancillary activities with IC50 values > 1 μM. [1] In vitro metabolism studies in monkey liver microsomes predicted low levels of oxidative defluorination; human liver microsomes showed even lower levels. [1] In vitro, MK-6240 demonstrates high affinity and selectivity for NFTs. Binding assays using post-mortem brain tissue from Alzheimer's disease patients show that MK-6240 binds specifically to tau aggregates. It does not bind significantly to amyloid-β plaques or other non-specific targets. Its high specificity makes it a valuable tool for tau imaging. |
| ln Vivo |
In rhesus monkeys (which do not exhibit tau pathology), PET studies with [18F]6 (radiolabeled MK-6240) demonstrated rapid distribution across the blood-brain barrier followed by rapid clearance. No white matter retention was observed; distribution was homogeneous across all brain regions. [1]
Pretreatment with non-radioactive compound 6 (1 mg/kg) blocked [18F]6 binding, as shown by reduced PET signal in summed images (90-120 min, sagittal view). [1] In vivo, MK-6240 is used as a PET tracer for the detection and quantification of tau pathology in the brain. It has been evaluated in clinical studies for the diagnosis and staging of Alzheimer's disease. PET imaging with MK-6240 allows for the non-invasive assessment of tau burden in living patients, which is important for diagnosis, prognosis, and monitoring of disease progression. |
| Enzyme Assay |
In vitro binding assays for MK-6240 are performed using post-mortem brain tissue homogenates from Alzheimer's disease patients, which contain NFTs. The tissue is incubated with radiolabeled MK-6240 (e.g., [¹⁸F]-MK-6240) and varying concentrations of unlabeled compound. Bound and free radioligand are separated by filtration, and radioactivity is counted. Kᵢ values are calculated from competition binding curves.
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| Cell Assay |
In vitro cell-based assays for MK-6240 are not standard, as its primary use is as a PET tracer rather than a pharmacological agent. However, cellular models of tau aggregation can be used to assess its binding specificity. Cells expressing mutant tau or treated with tau aggregation inducers are incubated with MK-6240, and binding is assessed by fluorescence microscopy or flow cytometry.
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| Animal Protocol |
PET imaging in rhesus monkeys: [18F]6 (radiolabeled MK-6240) was administered intravenously (dose not specified). Dynamic PET scans were acquired, and summed images (90-120 min) overlaid on MR images. For blocking studies, non-radioactive compound 6 was administered at 1 mg/kg prior to [18F]6 injection. Standardized uptake values (SUV) were measured. [1]
In vitro binding assays: Human AD cortex homogenates were used in competition binding assays with [3H]8 (Kd = 0.3 nM) or [3H]7 as radioligands. Saturation binding studies were performed with [3H]6. Non-specific binding was defined using 10 μM unlabeled compound 6 or compound 2. [1] P-gp efflux assay: LLC-PK1 cells expressing human or rat P-gp were used; transport was measured at 0.1 μM compound 6, with BA:AB ratio calculated. Permeability was measured in control LLC-PK1 cells. [1] Autoradiography: Human AD brain sections were incubated with [3H]6, with or without blocking agents (self-block or compound 2), then exposed to film. Immunostaining with PHF6 antibody was performed for comparison. [1] In vivo animal studies for MK-6240 are conducted in transgenic mouse models of tauopathy (e.g., P301S or rTg4510 mice). The compound is administered intravenously, and PET imaging is performed to assess brain uptake and binding to tau aggregates. Post-mortem brain tissue is analyzed to confirm specific binding to NFTs by autoradiography and immunohistochemistry. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic properties of MK-6240 are characterized as a PET tracer. Following intravenous administration, it rapidly enters the brain and binds to NFTs. It is cleared from the blood and non-target tissues, allowing for high-contrast imaging. Its half-life is appropriate for PET imaging studies. The compound is stable and is formulated for intravenous injection.
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| Toxicity/Toxicokinetics |
MK-6240 is a PET tracer and is generally well-tolerated at the tracer doses used for imaging. Radiation exposure from [¹⁸F]-MK-6240 is within acceptable limits for diagnostic imaging. As a research compound, it is intended for diagnostic use and is not for therapeutic applications. Standard radiation safety precautions should be followed when handling radiolabeled compound.
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| References |
J Med Chem.2016 May 26;59(10):4778-89.
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| Additional Infomation |
MK-6240 (CAS#: 1841078-87-2) is a fluorine-18 labeled PET tracer ([18F]-MK-6240) designed for in vivo quantification of neurofibrillary tangles (NFTs) in Alzheimer's disease. It has high specificity and selectivity for NFTs over β-amyloid, with suitable physicochemical properties (calculated CNS-MPO score 5.8, shake-flask logD 3.3) and favorable brain pharmacokinetics. Clinical studies evaluating [18F]6 as an NFT PET tracer in Alzheimer's disease patients were underway at the time of publication. [1]
MK-6240 is a PET tracer for neurofibrillary tangles (NFTs). It is also known as 6-Fluoro-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine. It exhibits high specificity and selectivity for binding to NFTs. It is used for the diagnosis and staging of Alzheimer's disease and other tauopathies. This product is for research and diagnostic use. |
| Molecular Formula |
C16H11FN4
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|---|---|
| Molecular Weight |
278.283746004105
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| Exact Mass |
278.096
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| CAS # |
1841078-87-2
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| PubChem CID |
118577045
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
21
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| Complexity |
379
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
KAXAUWZJVWGFDO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11FN4/c17-13-2-1-11-8-20-15(7-12(11)16(13)18)21-6-4-10-3-5-19-9-14(10)21/h1-9H,18H2
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| Chemical Name |
6-fluoro-3-pyrrolo[2,3-c]pyridin-1-ylisoquinolin-5-amine
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| Synonyms |
MK-6240; MK6240; MK 6240
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| HS Tariff Code |
2934.99.9001
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| 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)
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| 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
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| 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 | 3.5935 mL | 17.9675 mL | 35.9350 mL | |
| 5 mM | 0.7187 mL | 3.5935 mL | 7.1870 mL | |
| 10 mM | 0.3594 mL | 1.7968 mL | 3.5935 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.
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