Addictive behavior stems from abnormal signaling activities in the brain. Thus identification of compounds blocking this modified signaling activity may lead to treatments for addictive behavior. GPR35, a to-date uncharacterized orphan G-Protein Coupled Receptor, is thought to play a role in addiction and has homology to other known receptors of abuse. The goal of this project is to identify small molecule antagonists of GPR35, which may aid in characterization of this receptor and ultimately further the understanding of the role of GPR35 in addictive behavior. ..more
Related BioAssays
Related BioAssays
Target
Depositor Specified Assays
Show more |
| AID | Name | Type | Comment |
|---|---|---|---|
| 2058 | Image-Based HTS for Selective Antagonists of GPR35 | confirmatory | Image-Based HTS for Selective Antagonists of GPR35 |
| 2397 | SAR Analysis of Selective Antagonists of GPR55 using an Image-Based Assay | confirmatory | SAR Analysis of Selective Antagonists of GPR55 using an Image-Based Assay |
| 2480 | SAR analysis of Antagonists of the GPR35 Receptor using an Image-Based Assay - Set 2 | confirmatory | SAR analysis of Antagonists of the GPR35 Receptor using an Image-Based Assay - Set 2 |
| 463201 | SAR Analysis using an Image-based Vasopressin Agonist Counter Assay for the Identification of Selective Antagonists of the GPR35 Receptor | other | SAR Analysis using an Image-based Vasopressin Agonist Counter Assay for the Identification of Selective Antagonists of the GPR35 Receptor |
| 463202 | SAR Analysis using an Image-based Vasopressin Antagonist Counter Assay for the Identification of Selective Antagonists of the GPR35 Receptor | other | SAR Analysis using an Image-based Vasopressin Antagonist Counter Assay for the Identification of Selective Antagonists of the GPR35 Receptor |
| 463217 | SAR Analysis for the identification of Selective Antagonists of ERK1/2 Activity in GPR35-Overexpressing U2OS Cells | confirmatory | SAR Analysis for the identification of Selective Antagonists of ERK1/2 Activity in GPR35-Overexpressing U2OS Cells |
| 463227 | SAR analysis of Antagonists of the GPR35 Receptor using an Image-Based Assay - Set 5 | confirmatory | SAR analysis of Antagonists of the GPR35 Receptor using an Image-Based Assay - Set 5 |
| 463228 | SAR Analysis of Selective Antagonists of GPR55 using an Image-Based Assay - Set 3 | confirmatory | SAR Analysis of Selective Antagonists of GPR55 using an Image-Based Assay - Set 3 |
| 488987 | SAR Analysis for the identification of Selective Antagonists of ERK1/2 Activity in GPR35-Overexpressing U2OS Cells - Set 2 | confirmatory | SAR Analysis for the identification of Selective Antagonists of ERK1/2 Activity in GPR35-Overexpressing U2OS Cells - Set 2 |
Description:
Data Source: Sanford-Burnham Center for Chemical Genomics (SBCCG)
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1X01MH085708-01
Assay Provider: Dr. Lawrence Barak, Duke University
Addictive behavior stems from abnormal signaling activities in the brain. Thus identification of compounds blocking this modified signaling activity may lead to treatments for addictive behavior. GPR35, a to-date uncharacterized orphan G-Protein Coupled Receptor, is thought to play a role in addiction and has homology to other known receptors of abuse. The goal of this project is to identify small molecule antagonists of GPR35, which may aid in characterization of this receptor and ultimately further the understanding of the role of GPR35 in addictive behavior.
This AID summarizes SBCCG's probe development efforts to identify antagonists of the orphan receptor GPR35.
Three potential probes have been identified and probe reports have been submitted describing compound screening.
From the primary HTS and subsequent hit confirmation (AID 2058) several hit compounds were identified. Hits were clustered into scaffolds and SAR studies were performed on compounds from several scaffolds reconfirming potency (AID 2480). Compounds were further tested for selectivity against the related orphan receptor GPR55 (AID 2397). Three novel scaffolds were identified as GPR35 antagonists with CID2286812 (ML145) representing the very potent and selective probe for chemical series 1, CID1542103 (ML144) representing the potent and selective probe for chemical series 2, and CID9581011 (ML194) representing chemical series 3 with intermediate potency between the first two probes.
The probes were characterized further by two assays performed in the assay provider's and his collaborator's laboratories. Selectivity against an unrelated receptor Vasopressin IIa was evaluated for ML144 and ML145 in agonist (AID 463201) and antagonist (AID 463202) mode showing that neither probe agonizes nor antagonizes the vasopressin receptor. Additionally, downstream ERK1/2 phosphorylation activity of the probe compounds was determined (AID 463217) using an "in-cell" Western assay concluding that all three probes have measurable activity downstream in the authentic signaling pathway.
Details of protocols, compound structures, and results from the original assays can be found in PubChem at the respective AIDs listed below.
Source Affiliation: Sanford-Burnham Medical Research Institute (SBMRI, San Diego, CA)
Network: NIH Molecular Libraries Probe Production Centers Network (MLPCN)
Grant Proposal Number: 1X01MH085708-01
Assay Provider: Dr. Lawrence Barak, Duke University
Addictive behavior stems from abnormal signaling activities in the brain. Thus identification of compounds blocking this modified signaling activity may lead to treatments for addictive behavior. GPR35, a to-date uncharacterized orphan G-Protein Coupled Receptor, is thought to play a role in addiction and has homology to other known receptors of abuse. The goal of this project is to identify small molecule antagonists of GPR35, which may aid in characterization of this receptor and ultimately further the understanding of the role of GPR35 in addictive behavior.
This AID summarizes SBCCG's probe development efforts to identify antagonists of the orphan receptor GPR35.
Three potential probes have been identified and probe reports have been submitted describing compound screening.
From the primary HTS and subsequent hit confirmation (AID 2058) several hit compounds were identified. Hits were clustered into scaffolds and SAR studies were performed on compounds from several scaffolds reconfirming potency (AID 2480). Compounds were further tested for selectivity against the related orphan receptor GPR55 (AID 2397). Three novel scaffolds were identified as GPR35 antagonists with CID2286812 (ML145) representing the very potent and selective probe for chemical series 1, CID1542103 (ML144) representing the potent and selective probe for chemical series 2, and CID9581011 (ML194) representing chemical series 3 with intermediate potency between the first two probes.
The probes were characterized further by two assays performed in the assay provider's and his collaborator's laboratories. Selectivity against an unrelated receptor Vasopressin IIa was evaluated for ML144 and ML145 in agonist (AID 463201) and antagonist (AID 463202) mode showing that neither probe agonizes nor antagonizes the vasopressin receptor. Additionally, downstream ERK1/2 phosphorylation activity of the probe compounds was determined (AID 463217) using an "in-cell" Western assay concluding that all three probes have measurable activity downstream in the authentic signaling pathway.
Details of protocols, compound structures, and results from the original assays can be found in PubChem at the respective AIDs listed below.
Panel Information
GPR35_Panel
§ Panel component ID.
| Data Table(Active) Data Table(All) | Show more |
| PID§ | Name | Substance | Panel Targets | Description | ||
|---|---|---|---|---|---|---|
| Active | Inactive | |||||
| 1 | ML# | ML# for the compound | ||||
| 2 | AID_2480_IC50_1 | 2 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | ||
| 3 | AID_2480_IC50_2 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | |||
| 4 | AID_2480_IC50_3 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | |||
| 5 | AID_2397_IC50_1 | 1 | G-protein coupled receptor 55 [Homo sapiens] [gi:33695107] | IC50 value determined using sigmoidal dose response equation | ||
| 6 | AID_2397_IC50_2 | G-protein coupled receptor 55 [Homo sapiens] [gi:33695107] | IC50 value determined using sigmoidal dose response equation | |||
| 7 | AID_463217_IC50_1 | 1 | 1 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | |
| 8 | AID_463201_%_Activation_1 | 1 | vasopressin V2 receptor isoform 1 [Homo sapiens] [gi:4557345] | %Activation for the data set | ||
| 9 | AID_463201_%_Activation_2 | vasopressin V2 receptor isoform 1 [Homo sapiens] [gi:4557345] | %Activation for the data set | |||
| 10 | AID_463227_IC50_1 | 1 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | ||
| 11 | AID_463227_IC50_2 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | |||
| 12 | AID_463227_IC50_3 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | |||
| 13 | AID_488987_IC50_1 | 1 | G-protein coupled receptor 35 isoform a [Homo sapiens] [gi:33695097] | IC50 value determined using sigmoidal dose response equation | ||
| 14 | AID_463228_IC50_1 | 1 | G-protein coupled receptor 55 [Homo sapiens] [gi:33695107] | IC50 value determined using sigmoidal dose response equation | ||
| 15 | AID_463228_IC50_2 | G-protein coupled receptor 55 [Homo sapiens] [gi:33695107] | IC50 value determined using sigmoidal dose response equation | |||
§ Panel component ID.
Protocol
Please see pertinent AIDs: 2058, 2397, 2480, 463201, 463202, 463217, 463227, 463228, 488987
Comment
Probe molecules are defined as the positives of this assay and assigned a score of 100.
Result Definitions
| Show more |
| TID | Name | Description | PID§ | Panel Targets | Histogram | Type | Unit | |
|---|---|---|---|---|---|---|---|---|
| Outcome | The BioAssay activity outcome | Outcome | ||||||
| Score | The BioAssay activity ranking score |  | Integer | |||||
| 1 | ML# | ML# for the compound | 1 | String | ||||
| 2 | AID_2480_Outcome | The outcome for AID_2480 | 2 | G-protein coupled receptor 35 isoform a [Homo sapiens] | | Outcome | ||
| 3 | AID_2480_Qualifier_1 | This qualifier is to be used with the next TID, AID_2480_IC50_1. If the qualifier is ""="", the IC50 result equals the value in that column. If the qualifier is "">"", the IC50 result is greater than that value. If the qualifier is ""<"", the IC50 result is smaller than that value | 2 | String | ||||
| 4 | AID_2480_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 2 | | Float | μM | ||
| 5 | AID_2480_Qualifier_2 | This qualifier is to be used with the next TID, AID_2480_IC50_2. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 3 | G-protein coupled receptor 35 isoform a [Homo sapiens] | String | |||
| 6 | AID_2480_IC50_2 | IC50 value determined using a sigmoidal dose response equation | 3 | | Float | μM | ||
| 7 | AID_2480_Qualifier_3 | This qualifier is to be used with the next TID, AID_2480_IC50_3. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 4 | G-protein coupled receptor 35 isoform a [Homo sapiens] | String | |||
| 8 | AID_2480_IC50_3 | IC50 value determined using a sigmoidal dose response equation | 4 | | Float | μM | ||
| 9 | AID_2397_Outcome | The outcome for AID_2397 | 5 | G-protein coupled receptor 55 [Homo sapiens] | | Outcome | ||
| 10 | AID_2397_Qualifier_1 | This qualifier is to be used with the next TID, AID_2397_IC50_1. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 5 | String | ||||
| 11 | AID_2397_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 5 | | Float | μM | ||
| 12 | AID_2397_Qualifier_2 | This qualifier is to be used with the next TID, AID_2397_IC50_2. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 6 | G-protein coupled receptor 55 [Homo sapiens] | String | |||
| 13 | AID_2397_IC50_2 | IC50 value determined using a sigmoidal dose response equation | 6 | | Float | μM | ||
| 14 | AID_463217_Outcome | The outcome for AID_463217 | 7 | G-protein coupled receptor 35 isoform a [Homo sapiens] | | Outcome | ||
| 15 | AID_463217_Qualifier_1 | This qualifier is to be used with the next TID, AID_463217_IC50_1. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 7 | String | ||||
| 16 | AID_463217_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 7 | | Float | μM | ||
| 17 | AID_463201_Outcome | The outcome for AID_463201 | 8 | vasopressin V2 receptor isoform 1 [Homo sapiens] | | Outcome | ||
| 18 | AID_463201_%_Activation_1 | % Activation in AID_463201 | 8 | | Float | |||
| 19 | AID_463201_%_Activation_2 | % Activation in AID_463201 | 9 | vasopressin V2 receptor isoform 1 [Homo sapiens] | | Float | ||
| 20 | AID_463227_Outcome | The outcome for AID_463227 | 10 | G-protein coupled receptor 35 isoform a [Homo sapiens] | | Outcome | ||
| 21 | AID_463227_Qualifier_1 | This qualifier is to be used with the next TID, AID_463227_IC50_1. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 10 | String | ||||
| 22 | AID_463227_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 10 | | Float | μM | ||
| 23 | AID_463227_Qualifier_2 | This qualifier is to be used with the next TID, AID_463227_IC50_2. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 11 | G-protein coupled receptor 35 isoform a [Homo sapiens] | String | |||
| 24 | AID_463227_IC50_2 | IC50 value determined using a sigmoidal dose response equation | 11 | | Float | μM | ||
| 25 | AID_463227_Qualifier_3 | This qualifier is to be used with the next TID, AID_463227_IC50_3. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 12 | G-protein coupled receptor 35 isoform a [Homo sapiens] | String | |||
| 26 | AID_463227_IC50_3 | IC50 value determined using a sigmoidal dose response equation | 12 | | Float | μM | ||
| 27 | AID_488987_Outcome | The outcome for AID_488987 | 13 | G-protein coupled receptor 35 isoform a [Homo sapiens] | | Outcome | ||
| 28 | AID_488987_Qualifier_1 | This qualifier is to be used with the next TID, AID_488987_IC50_1. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 13 | String | ||||
| 29 | AID_488987_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 13 | | Float | μM | ||
| 30 | AID_463228_Outcome | The outcome for AID_463228 | 14 | G-protein coupled receptor 55 [Homo sapiens] | | Outcome | ||
| 31 | AID_463228_Qualifier_1 | This qualifier is to be used with the next TID, AID_463228_IC50_1. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 14 | String | ||||
| 32 | AID_463228_IC50_1 | IC50 value determined using a sigmoidal dose response equation | 14 | | Float | μM | ||
| 33 | AID_463228_Qualifier_2 | This qualifier is to be used with the next TID, AID_463228_IC50_2. If the qualifier is "=", the IC50 result equals the value in that column. If the qualifier is ">", the IC50 result is greater than that value. If the qualifier is "<", the IC50 result is smaller than that value | 15 | G-protein coupled receptor 55 [Homo sapiens] | String | |||
| 34 | AID_463228_IC50_2 | IC50 value determined using a sigmoidal dose response equation | 15 | | Float | μM |
Additional Information
Grant Number: 1X01MH085708-01
Classification
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