| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Kb: 1.4 nM (GluK1)[1]
GluK1 (formerly GluR5) kainate receptor subunit. UBP316 is a potent and selective orthosteric competitive antagonist of GluK1, with a Kb value of 1.4 nM. It has low affinity for GluK2, GluK3, and AMPA receptors. By blocking the GluK1 receptor, it inhibits the effects of endogenous glutamate and exogenous agonists such as ATPA on kainate receptor‑mediated synaptic transmission and modulation of GABAergic signaling. |
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| ln Vitro |
At all tested concentrations (up to 100 μM), UBP316 is ineffective at GluK2 (GluR6) receptors, while at 1 μM, it had no effect at GluK3 (GluR7) receptors[1]. Following repeated spikes, UBP316 (200 nM) lessens the pre-synaptic calcium transients' short-term facilitation[1]. In vitro, UBP316 successfully counteracts GluK1-mediated suppression of excitatory transmission in the hippocampal CA1 region[1]. Long-term potentiation (LTP) that is not dependent on NMDA receptors is inhibited by UBP316[1].
In vitro, UBP316 (10‑1000 nM) potently and selectively blocks the depression of field excitatory postsynaptic potentials (fEPSPs) induced by the selective GluK1 agonist ATPA in rat cortical or hippocampal brain slices. It also blocks the monosynaptically‑evoked GABAergic transmission that is mediated by GluK1 receptors. The Kb value for antagonism is 1.4 nM, making it one of the most potent GluK1 antagonists available. At concentrations up to 10 uM, it has no significant effect on AMPA or NMDA receptor‑mediated responses. |
| ln Vivo |
In vivo, UBP316 has been used to study the role of GluK1 receptors in pain (by intrathecal injection), in seizure susceptibility, and in synaptic plasticity. However, detailed in vivo activity data are limited, as the compound is typically used as an electrophysiological tool. In the spinal cord, blocking GluK1 receptors may reduce hyperalgesia and allodynia in chronic pain models. As a research tool, UBP316 has not been developed therapeutically.
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| Enzyme Assay |
Standard cell‑free kainate receptor binding assays for UBP316 use membranes from HEK‑293 cells stably expressing human GluK1 (GluR5). Membranes (15‑20 ug protein) are incubated with 5‑10 nM [3H]kainate ([3H]KA) or a selective GluK1 radioligand (e.g., [3H]ATPA) and varying concentrations of UBP316 (0.01‑1000 nM) in 50 mM Tris‑HCl buffer (pH 7.4) containing 2.5 mM CaCl2 and 5 mM MgCl2 for 60 min at 4degC. Non‑specific binding is determined with 1 mM L‑glutamate or 100 uM kainate. Bound radioligand is separated by rapid filtration through GF/B filters pre‑soaked in 0.5% polyethyleneimine, washed, and counted. IC50 values are calculated, and Ki is derived. For selectivity, parallel assays are performed on GluK2, GluK3, and AMPA receptor membranes. For functional antagonism studies, [3⁵S]GTPgammaS binding assays can be performed.
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| Cell Assay |
For cellular assays, HEK‑293 cells stably expressing human GluK1 are seeded in 96‑well plates (40,000 cells/well) in DMEM/10% FBS for 48 h. For calcium mobilization assays (with co‑expression of Galpha15), cells are loaded with Fluo‑4 AM (2.5 uM) in HBSS/HEPES for 60 min. Cells are pre‑incubated with UBP316 (0.1‑1000 nM) for 15 min, then stimulated with an EC80 concentration of ATPA (0.5‑5 uM). Fluorescence is measured. The IC50 for inhibition is calculated. For electrophysiology, whole‑cell voltage‑clamp recordings are made from GluK1‑expressing cells; UBP316 (1‑1000 nM) is co‑applied with ATPA (EC80), and the reduction in inward current is measured. The Kb value is 1.4 nM. For brain slice electrophysiology, rat hippocampal or cortical slices are placed in a recording chamber and perfused with aCSF. A stimulating electrode is placed in the Schaffer collateral pathway, and a recording electrode is placed in the CA1 stratum radiatum for field EPSP recording. UBP316 (100‑1000 nM) is added to the perfusate for 10‑20 min, then the GluK1 selective agonist ATPA (1‑10 uM) is added, and the depression of fEPSP amplitude is measured. UBP316 blocks the ATPA‑induced depression, with an IC50 in the low nM range.
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| Animal Protocol |
In vivo studies are performed in male Sprague‑Dawley rats (200‑300 g) for pain studies. UBP316 is formulated in sterile saline and administered intrathecally (IT) at doses of 1‑100 ug in 10‑20 uL volume via lumbar puncture. For the chronic constriction injury (CCI) model of neuropathic pain, rats are anesthetized, and the sciatic nerve is loosely ligated. After 7‑14 days, the paw withdrawal threshold to mechanical stimuli (von Frey filaments) and paw withdrawal latency to thermal stimuli (Hargreaves apparatus) are measured. UBP316 (10‑100 ug IT) is administered, and the withdrawal threshold/latency is measured at 15, 30, 60, 120, 240 min post‑injection. An increase (reversal of allodynia/hyperalgesia) indicates that GluK1 receptors are involved in the maintenance of neuropathic pain. For seizure studies, UBP316 (10‑100 ug ICV) is administered 30 min before a convulsant (e.g., pentylenetetrazole or kainate). Seizure latency and severity are recorded. For brain slice recordings, UBP316 is used ex vivo.
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| ADME/Pharmacokinetics |
UBP316 (ACET, MW 429.45, C20H19N3O6S) is a small molecule that is moderately soluble in DMSO (10 mg/mL) and sparingly soluble in water. As a willardiine derivative, it is stable at -20degC. The compound has low oral bioavailability and does not readily cross the BBB; it is typically used in vitro or administered intrathecally/intracerebroventricularly in vivo. The half‑life in the CNS after ICV injection is approximately 1‑2 hours.
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| Toxicity/Toxicokinetics |
Preclinical toxicity data are limited. UBP316 is not cytotoxic in cell culture at concentrations up to 10 uM. At intrathecal doses up to 100 ug in rats, no significant motor deficits or overt signs of toxicity are observed. Standard safety precautions for handling research chemicals should be followed. UBP316 is not approved for human use.
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| References | |
| Additional Infomation |
UBP316 (ACET, CAS 936095-50-0) is a potent and selective GluK1 (GluR5) kainate receptor antagonist (Kb = 1.4 nM). It is used as a research tool to study the role of GluK1 in synaptic plasticity, pain, and epilepsy. The compound has not entered clinical trials. Storage: desiccated at -20degC. The name ACET refers to the compound.
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| Molecular Formula |
C20H19N3O6S
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|---|---|
| Molecular Weight |
429.45
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| Exact Mass |
429.099
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| CAS # |
936095-50-0
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| PubChem CID |
16125102
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| Appearance |
White to off-white solid powder
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| Density |
1.474±0.06 g/cm3 (20 °C, 760 mmHg)
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| Boiling Point |
681.3±65.0 °C (760 mmHg)
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| Melting Point |
275-278 °C (decomp) (water)
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| LogP |
1.905
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
751
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| Defined Atom Stereocenter Count |
1
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| SMILES |
CC1=CN(C(=O)N(C1=O)CC2=C(SC(=C2)C3=CC=CC=C3)C(=O)O)C[C@@H](C(=O)O)N
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| InChi Key |
LCZDCKMQSBGXAH-AWEZNQCLSA-N
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| InChi Code |
InChI=1S/C20H19N3O6S/c1-11-8-22(10-14(21)18(25)26)20(29)23(17(11)24)9-13-7-15(30-16(13)19(27)28)12-5-3-2-4-6-12/h2-8,14H,9-10,21H2,1H3,(H,25,26)(H,27,28)/t14-/m0/s1
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| Chemical Name |
3-[[3-[(2S)-2-amino-2-carboxyethyl]-5-methyl-2,6-dioxopyrimidin-1-yl]methyl]-5-phenylthiophene-2-carboxylic acid
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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) |
1M NaOH: 80 mg/mL (186.28 mM)
DMSO: 2 mg/mL (4.66 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.2 mg/mL (0.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 2.0 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. Solubility in Formulation 2: ≥ 0.2 mg/mL (0.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 2.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.2 mg/mL (0.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3286 mL | 11.6428 mL | 23.2856 mL | |
| 5 mM | 0.4657 mL | 2.3286 mL | 4.6571 mL | |
| 10 mM | 0.2329 mL | 1.1643 mL | 2.3286 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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