| # | Aladdin ID | Assay Type | Description | Organism | Compounds | Reference | BAO Format | Source | |
|---|---|---|---|---|---|---|---|---|---|
| 1. | ALA3888383 | B | Cell Based Assay: TRKA co-expressed with p75: The assays are based upon DiscoveRx's proprietary Enzyme Fragment Complementation (EFC) technology. In the case of the TRK cell lines, the enzyme acceptor (EA) protein is fused to a SH2 protein and the TRK receptor of interest has been tagged with a Prolink tag. Cryopreserved PathHunter cells are used from either in-house produced batches or bulk batches bought directly from DiscoveRx. Cryopreserved cells are resuscitated, spun 1000 rpm for 4 min to remove freezing media, and resuspended in MEM+0.5% horse serum (both Invitrogen) to 5e^5 cells/ml. The cells are then plated using a Multidrop into Greiner white tissue culture treated plates at 20 μl/well and incubated for 24 h at 37 °C., 5% CO2, high humidity. On the day of the assay, the cell plates are allowed to cool to room temperature for 30 min prior to the assay. 4 mM stock solutions of test compounds are prepared and serially diluted in 100% DMSO. A standard curve using the compound of Example 135, WO2005/116035 at a top concentration of 150 μM is also prepared on each test plate. High percentage effect (HPE) is defined by 150 μM of the compound of Example 135, WO2005/116035 and 0% effect (ZPE) is defined by 100% DMSO. Plates containing 1 μl of serially diluted compound, standard and HPE/ZPE are diluted 1/66 in assay buffer (PBS minus Ca2+, minus Mg2+ with 0.05% pluronic F127) using a Wellmate. Using a Platemate Plus, 5 μl of 1/66 diluted test compounds is then transferred to the cell plate and allowed to reach equilibrium by incubating for 30 min at room temperature before addition of agonist stimulus: 10 μl/well of 2 nM (0.571 nM FAC) of the cognate neurotrophin (Peprotech) diluted in agonist buffer (HBSS with 0.25% BSA). Final assay concentration of the test compounds is 8.66 μM, (the compound of Example 135, WO2005/116035 FAC is 0.325 μM). The plates are left at room temperature for a further 2 hours before addition of 10 μl of the DiscoveRx PathHunter detection reagent (made up by adding 1 part Galacton Star, 5 parts Emerald II and 19 parts Cell Assay Buffer as per the manufacturer's instructions). After reagent addition, plates are covered and incubated at room temperature for 60 minutes. Luminescence signal is read using an Envision. | 794 | assay format | BindingDB Database | |||
| 2. | ALA4309191 | B | Antagonist activity at prolink-tagged TrkA (unknown origin) expressed in cells assessed as inhibition of NGF-induced receptor phosphorylation by measuring reduction in EA-tagged SH2 protein recruitment preincubated for 30 mins followed by NGF addition measured after 2 hrs by PathHunter enzyme complementation assay | Homo sapiens | 25 | cell-based format | Scientific Literature | ||
| 3. | ALA4309194 | B | Selectivity ratio of IC50 for TrkB (unknown origin) to IC50 for TrkA (unknown origin) | Homo sapiens | 24 | assay format | Scientific Literature | ||
| 4. | ALA4309195 | B | Selectivity ratio of IC50 for TrkC (unknown origin) to IC50 for TrkA (unknown origin) | Homo sapiens | 23 | assay format | Scientific Literature | ||
| 5. | ALA4309196 | B | Binding affinity to C-terminal-His6/N-terminal BAP-tagged unphosphorylated TrkA (unknown origin) (441 to 796 residues) assessed as association constant by SPR analysis | Homo sapiens | 2 | single protein format | Scientific Literature | ||
| 6. | ALA4309197 | B | Binding affinity to C-terminal-His6/N-terminal BAP-tagged unphosphorylated TrkA (unknown origin) (441 to 796 residues) assessed as dissociation constant by SPR analysis | Homo sapiens | 2 | single protein format | Scientific Literature | ||
| 7. | ALA4309198 | B | Binding affinity to C-terminal-His6/N-terminal BAP-tagged unphosphorylated TrkA (unknown origin) (441 to 796 residues) by SPR analysis | Homo sapiens | 2 | single protein format | Scientific Literature | ||
| 8. | ALA4309199 | B | Antagonist activity at human His-tagged TrkA (441 to 796 residues) expressed in baculovirus expression system at 1 uM preincubated for 20 mins followed by TK-substrate-Biotin addition and measured after 35 mins by HTRF assay relative to control | Homo sapiens | 2 | assay format | Scientific Literature | ||
| 9. | ALA4309201 | B | Antagonist activity at unphosphorylated human His-tagged TrkA (441 to 796 residues) expressed in baculovirus expression system preincubated for 20 mins followed by TK-substrate-Biotin addition and measured after 35 mins by HTRF assay | Homo sapiens | 2 | assay format | Scientific Literature | ||
| 10. | ALA4309202 | B | Antagonist activity at phosphorylated human His-tagged TrkA (441 to 796 residues) expressed in baculovirus expression system preincubated for 20 mins followed by TK-substrate-Biotin addition and measured after 35 mins by HTRF assay | Homo sapiens | 2 | assay format | Scientific Literature | ||
| 11. | ALA4309203 | B | Ratio of IC50 for phosphorylated human His-tagged TrkA (441 to 796 residues) expressed in baculovirus expression system to IC50 for unphosphorylated human His-tagged TrkA (441 to 796 residues) expressed in baculovirus expression system | Homo sapiens | 2 | assay format | Scientific Literature | ||
| 12. | ALA4309204 | A | Apparent intrinsic clearance in human liver microsomes at 1 uM in presence of NADP+ by LC-MS/MS analysis | Homo sapiens | 24 | microsome format | Scientific Literature | ||
| 13. | ALA4309205 | A | Intrinsic clearance in human hepatocytes assessed per million cells at 1 uM in presence of NADP+ by LC-MS/MS analysis | Homo sapiens | 23 | cell-based format | Scientific Literature | ||
| 14. | ALA4309207 | A | Apparent permeability from apical to basolateral side in RRCK cells | Canis lupus familiaris | 24 | cell-based format | Scientific Literature | ||
| 15. | ALA4309208 | A | Efflux ratio of apparent permeability MDCK cells harboring human MDR1 | Canis lupus familiaris | 24 | cell-based format | Scientific Literature | ||
| 16. | ALA4309209 | A | Efflux ratio of apparent permeability MDCK cells harboring human BCRP | Canis lupus familiaris | 24 | cell-based format | Scientific Literature | ||
| 17. | ALA4309210 | P | Lipophilicity, log D of the compound at pH 7.4 | 24 | small-molecule physicochemical format | Scientific Literature | |||
| 18. | ALA4309212 | A | Unbound brain to plasma concentration ratio in rat 0.5 mg/kg, iv infused for 4 hrs | Rattus norvegicus | 2 | organism-based format | Scientific Literature | ||
| 19. | ALA4309214 | A | Half life in rat 0.5 mg/kg, iv | Rattus norvegicus | 2 | organism-based format | Scientific Literature | ||
| 20. | ALA4309216 | A | Clearance in rat 0.5 mg/kg, iv | Rattus norvegicus | 2 | organism-based format | Scientific Literature |
The page will load shortly, Thanks for your patience!