UCB1244283

UCB1244283 (100 µM-1 mM; 30 minutes on ice) binds a distinct allosteric site in human SV2A_EM and stabilizes a closed conformation that reshapes the orthosteric pocket^[1].
UCB1244283 (30 µM; 2 hours at 4°C) increases the ³H-UCB-J binding capacity and affinity of SV2A in HEK293-derived membranes, with K_d decreasing from 19.9 to 11.1 nM^[1].
UCB1244283 (30 µM) modulation of ³H-UCB-J binding in HEK293-derived SV2A membranes requires Phe188, Tyr461, and Ser601; substitution of Leu655 with glutamine abolishes this modulation, whereas substitution of Leu655 with alanine does not impair this modulation^[1].
UCB1244283 (30 µM; 2 hours at 4°C) slows the dissociation of ³H-UCB-J from SV2A_WT in HEK293-derived membranes, extending t_1/2 from 2.0 minutes to 5.3 minutes^[1].
UCB1244283 (10-30 µM; 30 minutes on ice) reduces the binding rate of ³H-UCB-J to SV2A_EM in HEK293-derived membranes while more strongly slowing dissociation, favoring increased orthosteric site occupancy^[1].
UCB1244283 (0-500 µM) dose-dependently displaces the binding of ³H-padsevonil to SV2A from SV2A-expressing membranes^[1].
UCB1244283 (increasing concentrations; 120 minutes at 4°C; 60 minutes at 25°C or 37°C) positively modulates [³H]UCB30889 binding in rat cortical membranes, with a pEC₅₀ of 4.75 at 4°C^[2].
UCB1244283 (increasing concentrations; 120 minutes at 4°C; 60 minutes at 25°C or 37°C) positively modulates the binding of [³H]UCB30889 to human recombinant SV2A in HEK membranes, with a pEC₅₀ of 5.72 at 4°C^[2].
UCB1244283 (increasing concentrations; 120 minutes at 4°C; 60 minutes at 25°C or 37°C) positively modulates the binding of [³H]UCB30889 to rat recombinant SV2A in HEK membranes, with a pEC₅₀ of 6.05 at 4°C^[2].
UCB1244283 (10 μM; 120 minutes at 4°C or 60 minutes at 37°C) increases the affinity and B_max of [³H]UCB30889 in rat cortical membranes, with K_d decreasing from 88 nM to 37 nM at 4°C^[2].
UCB1244283 (10 μM; 120 minutes at 4°C or 60 minutes at 37°C) increases the affinity of human recombinant SV2A in HEK membranes for [³H]UCB30889, with K_d decreasing from 64 nM to 13 nM at 4°C^[2].
UCB1244283 (10 μM; 120 minutes at 4°C or 60 minutes at 37°C) enhances the affinity of UCB30889 in rat cortical membranes (pK_i increases from 7.03 to 7.36 at 4°C), but does not enhance the affinity of LEV^[2].
UCB1244283 (10 μM; 120 minutes at 4°C or 60 minutes at 37°C) enhances the affinity of human recombinant SV2A in HEK membranes for UCB30889 (pK_i increases from 6.85 to 7.79 at 4°C), whereas LEV affinity remains essentially unchanged^[2].
UCB1244283 (10 μM; 25°C) slows the binding and dissociation kinetics of [³H]UCB30889 on rat cortical SV2A, extending the slow dissociation t_1/2 from 3.50 minutes to 12.92 minutes^[2].
UCB1244283 (10 μM; 25°C) slows the dissociation kinetics of [³H]UCB30889 from human recombinant SV2A in HEK membranes, with a slow-phase t_1/2 of 16.3 minutes^[2].
UCB1244283 (30 μM; 120 minutes at 4°C) allosterically increases [³H]BRV affinity in wild-type and K694A/I273A/S294A human SV2A membranes, and increases the B_max of [³H]LEV in wild-type but not in K694A, I273A, or S294A mutants, demonstrating mutation-dependent differential modulation of BRV and LEV binding^[3].
UCB1244283 (increasing concentrations; 120 minutes) concentration-dependently enhances the binding of [³H]LEV and [³H]BRV in HEK293/SV2A membranes, approaching the maximal effect at 30 μM^[4].
UCB1244283 (30 μM; 120 minutes) increases [³H]LEV affinity (K_d 2,480 to 897 nM) and B_max (67 to 141 pmol/mg protein) in HEK293/SV2A membranes, while increasing [³H]BRV affinity (K_d 187 to 20 nM) and B_max (127 to 172 pmol/mg protein)^[4].
UCB1244283 (30 μM; 120 minutes) increases the B_max of [³H]LEV in human meninges (normalized value 100 to 174) without changing K_d (1,290 to 1,540 nM), and increases [³H]BRV affinity (K_d 84 to 32 nM) and B_max (normalized value 140 to 195)^[4].
UCB1244283 (30 μM; 30-minute preincubation) significantly slows the association and dissociation of [³H]BRV in HEK293/SV2A membranes, while having minimal effect on the association/dissociation kinetics of [³H]LEV^[4].
UCB1244283 (30 µM) reduces the binding affinity of [³H]padsevonil in membranes of HEK cells expressing human SV2A (K_d 2.3 to 3.90 nM) without altering B_max^[7].
UCB1244283 acts as a positive allosteric modulator of SV2A, increasing the affinity of [³H]BRV by 10-fold and the affinity of [³H]LEV by 2-fold.
UCB1244283 (30 µM; 60 minutes at 4 °C; heating for 15 minutes) preferentially stabilizes the BRV-bound complex in tsA201 membranes expressing SV2AΔ64-mVenus, where D670A but not W300A shows a modest LEV/UCB1244283-dependent increase^[8].
UCB1244283 (30 µM; 2 hours) approximately doubles the B_max of ³H-LEV in SV2AΔ64-mVenus tsA201 membranes and gives a K_d of 3.8 µM for LEV^[8].
UCB1244283 (1 nM-30 µM; 45 minutes on ice) enhances ³H-LEV binding with an EC₅₀ = 0.7 µM in wild-type SV2AΔ64-mVenus, whereas F184A and F188A reduce the EC₅₀ to 0.20 and 0.07 µM, respectively^[8].
UCB1244283 (30 µM) does not enhance ³H-LEV binding in tsA201 membranes expressing SV2AΔ64-D670A or -W300A, which is consistent with the absence of a second LEV binding site^[8].
UCB1244283 (at saturating concentration) does not change the affinity of ³H-UCB-J in SV2A membranes, with a K_d of 6 nM under saturating conditions versus 5.3 nM under baseline conditions^[8].
UCB1244283 (30 µM; 30 minutes on ice) binds in the luminal vestibule above BRV in the 3.05 Å SV2A-BRV structure, whereas no allosteric density is observed in the 2.91 Å SV2A-UCB7361 structure^[8].