| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
| Targets |
mGlu5
HTL14242 targets the metabotropic glutamate receptor 5 (mGlu5), a G-protein-coupled receptor that plays a key role in modulating glutamatergic neurotransmission. By acting as a negative allosteric modulator, it binds to an allosteric site on the receptor and reduces its activity, thereby dampening excessive glutamate signaling implicated in various neurological disorders. |
|---|---|
| ln Vitro |
In vitro cytotoxicity studies on HepG2 cells show that HTL14242 is stable in rat plasma, inactive at the hERG ion-channel, and has a clean profile with a TC50 of >90 μM[1].
In vitro, HTL14242 exhibits high potency at mGlu5, with a pKi of 9.3 and a pIC50 of 9.2. These values correspond to Ki and IC50 in the sub-nanomolar range, indicating extremely high affinity and potency. Its oral activity and advanced status make it a promising candidate for in vivo studies. |
| ln Vivo |
With an estimated ED50 of 0.3 mg/kg, HTL14242 (oral administration; 1, 3, or 10 mg/kg; sacrificed 1 h postdose) exhibits an excellent, dose-dependent occupancy of mGlu5 receptors from an oral dose[1]. (oral dosing; 1 mg/ml) shows an oral PK Profile in dogs; the t1/2, AUCinf, and F% are, respectively, 6.5 hours, 3946 ng/h/mL, and 80%[1].
In vivo, HTL14242 is being investigated for the treatment of Parkinson's disease. By modulating mGlu5 activity, it can help alleviate the motor symptoms associated with the disease, such as dyskinesia and levodopa-induced motor fluctuations. Its oral bioavailability supports convenient dosing in preclinical models. |
| Enzyme Assay |
mGlu5 binding affinity is determined using radioligand binding assays. Membrane preparations from cells expressing human mGlu5 are incubated with a radiolabeled antagonist (e.g., [³H]-MPEP) and varying concentrations of HTL14242. The Ki value is calculated from competitive binding curves, and the pKi is determined.
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| Cell Assay |
The functional activity of HTL14242 is assessed using cells expressing mGlu5, such as CHO cells. The compound's ability to inhibit mGlu5-mediated intracellular calcium mobilization is measured using a fluorescent calcium indicator (e.g., Fluo-4). The IC50 is calculated from the dose-response curve, and the pIC50 is determined.
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| Animal Protocol |
Animal/Disease Models: Dog ( PK study)[1]
Doses: 3, 10 and 30 mg/kg Route of Administration: Oral administration; single dose Experimental Results: Had a good PK characteristics in dogs. In vivo efficacy is evaluated in animal models of Parkinson's disease, such as the 6-hydroxydopamine (6-OHDA) lesioned rat model. HTL14242 is administered orally, and its effects on motor function are assessed using behavioral tests such as the rotational behavior test or the stepping test. |
| ADME/Pharmacokinetics |
As an orally active small molecule, HTL14242 is expected to have good oral bioavailability and favorable pharmacokinetic properties. Its molecular weight of 310.71 g/mol is within the range for good permeability, and its half-life is likely suitable for once- or twice-daily dosing.
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| Toxicity/Toxicokinetics |
As an mGlu5 NAM, potential toxicities may include central nervous system effects such as dizziness, somnolence, and cognitive impairment, which are common with modulators of glutamatergic signaling. However, its high potency may allow for lower doses, minimizing these effects.
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| References |
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| Additional Infomation |
HTL14242 is a research compound for the potential treatment of Parkinson's disease. It is an advanced mGlu5 NAM with high potency and oral activity. It serves as a valuable tool for studying the role of mGlu5 in neurological disorders and for developing new therapies.
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| Molecular Formula |
C16H8CLFN4
|
|---|---|
| Molecular Weight |
310.712924957275
|
| Exact Mass |
310.042
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| CAS # |
1644645-32-8
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| PubChem CID |
86763358
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| Appearance |
White to yellow solid powder
|
| LogP |
2.9
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
22
|
| Complexity |
426
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
ClC1C=C(C#N)C=C(C=1)C1C=C(C2C=CC(=CN=2)F)N=CN=1
|
| InChi Key |
FQAXDSVNYVVQSE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H8ClFN4/c17-12-4-10(7-19)3-11(5-12)15-6-16(22-9-21-15)14-2-1-13(18)8-20-14/h1-6,8-9H
|
| Chemical Name |
3-chloro-5-[6-(5-fluoropyridin-2-yl)pyrimidin-4-yl]benzonitrile
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| Synonyms |
HTL 14242 HTL-14242 HTL0014242HTL-0014242 HTL14242
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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) |
DMSO : ~12.5 mg/mL (~40.23 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (4.02 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.2184 mL | 16.0922 mL | 32.1844 mL | |
| 5 mM | 0.6437 mL | 3.2184 mL | 6.4369 mL | |
| 10 mM | 0.3218 mL | 1.6092 mL | 3.2184 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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