RGS8

Summary

RGS8 (regulator of G protein signaling 8, HGNC:16810) is a protein-coding gene on chromosome 1q25.3, encoding Regulator of G-protein signaling 8 (P57771). Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2.

This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. They accelerate transit through the cycle of GTP binding and hydrolysis to GDP, thereby terminating signal transduction, but paradoxically, also accelerate receptor-stimulated activation.

Source: NCBI Gene 85397 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 17 total
• Druggable target: yes
• MANE Select transcript: NM_001102450

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16810
Approved symbol	RGS8
Name	regulator of G protein signaling 8
Location	1q25.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC119067, MGC119068, MGC119069
Ensembl gene	ENSG00000135824
Ensembl biotype	protein_coding
OMIM	607189
Entrez	85397

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000258302, ENST00000367556, ENST00000367557, ENST00000483095, ENST00000491420, ENST00000508450, ENST00000515211

RefSeq mRNA: 6 — MANE Select: NM_001102450 NM_001102450, NM_001369564, NM_001387847, NM_001387848, NM_001387849, NM_033345

CCDS: CCDS1349, CCDS41443

Canonical transcript exons

ENST00000515211 — 8 exons

Exon	Start	End
ENSE00000822822	182648137	182648303
ENSE00001836695	182684352	182684587
ENSE00002074474	182672819	182672932
ENSE00003466665	182671657	182671730
ENSE00003472794	182666872	182666973
ENSE00003566086	182665969	182666033
ENSE00003683799	182669624	182669752
ENSE00003963640	182641818	182646917

Expression profiles

Bgee: expression breadth ubiquitous, 120 present calls, max score 97.61.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0160 / max 89.2978, expressed in 107 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16167	0.5238	81
16163	0.2946	74
16162	0.0937	35
16166	0.0326	8
16164	0.0311	16
16161	0.0290	16
16165	0.0112	3

Top tissues by expression

229 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.61	gold quality
nucleus accumbens	UBERON:0001882	87.33	gold quality
pons	UBERON:0000988	85.02	gold quality
putamen	UBERON:0001874	84.47	gold quality
caudate nucleus	UBERON:0001873	84.34	gold quality
cerebellar vermis	UBERON:0004720	81.93	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.35	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.55	gold quality
sperm	CL:0000019	77.86	silver quality
substantia nigra pars reticulata	UBERON:0001966	77.71	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.54	gold quality
substantia nigra pars compacta	UBERON:0001965	74.89	gold quality
hypothalamus	UBERON:0001898	74.77	gold quality
substantia nigra	UBERON:0002038	74.20	gold quality
prefrontal cortex	UBERON:0000451	74.05	gold quality
midbrain	UBERON:0001891	74.01	gold quality
dorsal plus ventral thalamus	UBERON:0001897	73.16	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	72.13	gold quality
lateral globus pallidus	UBERON:0002476	71.74	gold quality
cerebellum	UBERON:0002037	70.67	gold quality
forebrain	UBERON:0001890	70.41	gold quality
brain	UBERON:0000955	70.36	gold quality
Brodmann (1909) area 46	UBERON:0006483	70.36	gold quality
cerebellar cortex	UBERON:0002129	70.20	gold quality
ventral tegmental area	UBERON:0002691	70.16	gold quality
spinal cord	UBERON:0002240	69.90	gold quality
cerebellar hemisphere	UBERON:0002245	69.90	gold quality
anterior cingulate cortex	UBERON:0009835	69.40	gold quality
frontal cortex	UBERON:0001870	69.32	gold quality
neocortex	UBERON:0001950	68.99	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

152 targeting RGS8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-651-3P	99.94	73.48	5177

Literature-anchored findings (GeneRIF, showing 4)

• Spinophilin was identified as an RGS8-interacting protein. (PMID:18834863)
• Missense mutations in RGS8 gene is associated with breast cancer. (PMID:21135262)
• The chimeric RGS8 domains containing the first or the second exon part of RGS5 showed strong inhibitory effects similar to that of wild type RGS8, but the chimeric domain with the third exon part of RGS5 lost its activity (PMID:26754208)
• Key molecules associated with thyroid carcinoma prognosis: A study based on transcriptome sequencing and GEO datasets. (PMID:36059514)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rgs8	ENSDARG00000070037
mus_musculus	Rgs8	ENSMUSG00000042671
rattus_norvegicus	Rgs8	ENSRNOG00000002369

Paralogs (23): RGS11 (ENSG00000076344), RGS1 (ENSG00000090104), RGS17 (ENSG00000091844), AXIN1 (ENSG00000103126), RGS9 (ENSG00000108370), RGS2 (ENSG00000116741), RGS4 (ENSG00000117152), RGSL1 (ENSG00000121446), RGS13 (ENSG00000127074), RGS22 (ENSG00000132554), RGS3 (ENSG00000138835), RGS5 (ENSG00000143248), RGS16 (ENSG00000143333), RGS20 (ENSG00000147509), RGS10 (ENSG00000148908), RGS18 (ENSG00000150681), RGS12 (ENSG00000159788), AXIN2 (ENSG00000168646), RGS14 (ENSG00000169220), RGS19 (ENSG00000171700), RGS6 (ENSG00000182732), RGS7 (ENSG00000182901), RGS21 (ENSG00000253148)

Protein

Protein identifiers

Regulator of G-protein signaling 8 — P57771 (reviewed: P57771)

All UniProt accessions (2): D6RD36, P57771

UniProt curated annotations — full annotation on UniProt →

Function. Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Modulates the activity of potassium channels that are activated in response to DRD2 and CHRM2 signaling.

Subunit / interactions. Interacts with GNAO1. Interacts with GNAI3.

Subcellular location. Cell membrane. Membrane. Perikaryon. Cell projection. Dendrite. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
P57771-1	1	yes
P57771-2	2

RefSeq proteins (6): NP_001095920, NP_001356493, NP_001374776, NP_001374777, NP_001374778, NP_203131 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016137	RGS	Domain
IPR024066	RGS_subdom1/3	Homologous_superfamily
IPR034949	RGS_RGS8	Domain
IPR036305	RGS_sf	Homologous_superfamily
IPR044926	RGS_subdomain_2	Homologous_superfamily

Pfam: PF00615

UniProt features (16 total): helix 9, turn 3, chain 1, domain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2IHD	X-RAY DIFFRACTION	1.7
2ODE	X-RAY DIFFRACTION	1.9
5DO9	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P57771-F1	81.96	0.65

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 26

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 162 (showing top): AHRARNT_01, MYAATNNNNNNNGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, AP1_01, GCANCTGNY_MYOD_Q6, GOBP_REGULATION_OF_GTPASE_ACTIVITY, AP2_Q3, LHX3_01, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY, GOBP_REGULATION_OF_HYDROLASE_ACTIVITY, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION

GO Biological Process (5): G protein-coupled receptor signaling pathway (GO:0007186), G protein-coupled acetylcholine receptor signaling pathway (GO:0007213), negative regulation of signal transduction (GO:0009968), positive regulation of GTPase activity (GO:0043547), regulation of dopamine receptor signaling pathway (GO:0060159)

GO Molecular Function (3): GTPase activity (GO:0003924), GTPase activator activity (GO:0005096), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), plasma membrane (GO:0005886), cytoplasmic side of plasma membrane (GO:0009898), dendrite (GO:0030425), neuronal cell body membrane (GO:0032809), perikaryon (GO:0043204), synapse (GO:0045202), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
signal transduction	2
GTPase activity	2
neuronal cell body	2
G protein-coupled receptor activity	1
G protein-coupled receptor signaling pathway	1
G protein-coupled acetylcholine receptor activity	1
acetylcholine receptor signaling pathway	1
regulation of signal transduction	1
negative regulation of cell communication	1
negative regulation of signaling	1
negative regulation of response to stimulus	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
G protein-coupled dopamine receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
ribonucleoside triphosphate phosphatase activity	1
enzyme activator activity	1
GTPase regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
plasma membrane	1
cytoplasmic side of membrane	1
neuron projection	1
dendritic tree	1
cell body membrane	1
cell junction	1

Protein interactions and networks

STRING

1990 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RGS8	GNB5	O14775	880
RGS8	GNAO1	P09471	854
RGS8	SUCLG2	Q96I99	853
RGS8	GNAQ	P50148	796
RGS8	ARHGEF1	Q92888	795
RGS8	RGSL1	A5PLK6	792
RGS8	ARHGEF11	O15085	788
RGS8	GRK2	P25098	761
RGS8	RGS7BP	Q6MZT1	729
RGS8	MCF2	P10911	721
RGS8	GNA13	Q14344	709
RGS8	PLEK	P08567	689
RGS8	ARHGEF25	Q86VW2	674
RGS8	PLEK2	Q9NYT0	660
RGS8	AKAP10	O43572	658

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RGS8	GOLGA2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA2	RGS8	psi-mi:“MI:0915”(physical association)	0.560
Gnao1	RGS8	psi-mi:“MI:0407”(direct interaction)	0.440
PARP1	RGS8	psi-mi:“MI:0915”(physical association)	0.400
NXT2	RGS8	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): RGS8 (Two-hybrid), RGS8 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), RGS8 (Affinity Capture-MS), RGS8 (Synthetic Lethality), RGS8 (Two-hybrid), UHMK1 (Two-hybrid), GOLGA2 (Two-hybrid), CCDC85B (Two-hybrid), PLEKHF2 (Two-hybrid), KRT40 (Two-hybrid), RGS8 (Proximity Label-MS), RGS8 (Affinity Capture-MS), RGS8 (PCA)

ESM2 similar proteins: F1S668, O08849, O08850, O08899, O15492, O15539, O43665, O46471, O70521, O94810, P41220, P49795, P49798, P49799, P49800, P49804, P49806, P56700, P57771, P97428, P97844, Q08116, Q08DC7, Q0P5H5, Q0R4E4, Q29RM9, Q3S853, Q3T0T8, Q4L0E8, Q4R525, Q5R747, Q5RB40, Q6DGI0, Q6RG78, Q7SZC6, Q864Z2, Q8BXT1, Q92619, Q95K68, Q99PG4

Diamond homologs: A1A643, F1S668, O08773, O08774, O08849, O08850, O08899, O14921, O14924, O15169, O15492, O15539, O35625, O42400, O43566, O43665, O46469, O46470, O46471, O54828, O54829, O70239, O70240, O70521, O75916, O76081, O88566, O94810, P34295, P41220, P49758, P49795, P49796, P49797, P49798, P49799, P49800, P49802, P49803, P49804

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

17 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	15
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1298 predictions. Top by Δscore:

Variant	Effect	Δscore
1:182646915:TACC:T	acceptor_loss	1.0000
1:182646917:CCTA:C	acceptor_loss	1.0000
1:182646919:T:G	acceptor_loss	1.0000
1:182648138:T:TA	donor_gain	1.0000
1:182648139:C:A	donor_gain	1.0000
1:182648179:ATGGG:A	donor_gain	1.0000
1:182648299:CCCAT:C	acceptor_gain	1.0000
1:182648300:CCATC:C	acceptor_gain	1.0000
1:182648301:CAT:C	acceptor_gain	1.0000
1:182648303:TCTG:T	acceptor_loss	1.0000
1:182648304:CTGCG:C	acceptor_loss	1.0000
1:182648310:A:AC	acceptor_gain	1.0000
1:182648310:A:C	acceptor_gain	1.0000
1:182648312:G:C	acceptor_gain	1.0000
1:182648312:G:GC	acceptor_gain	1.0000
1:182665968:CA:C	donor_gain	1.0000
1:182671655:A:AC	donor_gain	1.0000
1:182671655:ACTGT:A	donor_gain	1.0000
1:182671656:C:CA	donor_gain	1.0000
1:182671656:CTGT:C	donor_gain	1.0000
1:182671656:CTGTC:C	donor_gain	1.0000
1:182648132:CACA:C	donor_loss	0.9900
1:182648133:ACAC:A	donor_loss	0.9900
1:182648134:CACC:C	donor_loss	0.9900
1:182648135:A:AG	donor_loss	0.9900
1:182648156:T:TA	donor_gain	0.9900
1:182648217:T:TA	donor_gain	0.9900
1:182648300:CCAT:C	acceptor_gain	0.9900
1:182648301:CATC:C	acceptor_gain	0.9900
1:182648304:C:CC	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000029214 (1:182710376 T>A), RS1000045687 (1:182740572 T>A), RS1000062751 (1:182730486 G>A), RS1000082795 (1:182653088 T>C), RS1000165561 (1:182655085 C>A), RS1000190565 (1:182694954 T>C), RS1000204240 (1:182675203 A>G), RS1000204521 (1:182743388 T>A,C), RS1000204846 (1:182701548 G>A,T), RS1000209571 (1:182693862 T>C), RS1000236310 (1:182659192 G>A,C), RS1000311828 (1:182652501 C>T), RS1000346219 (1:182661206 G>A,T), RS1000354717 (1:182723830 G>A), RS1000369287 (1:182673115 C>T)

Disease associations

OMIM: gene MIM:607189 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST007565_110	Morning person	1.000000e-28
GCST012180_2	Cigarettes smoked per day in Schizophrenia	5.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0006525	cigarettes per day measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2034803 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — R4 family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
CCG-50014	Inhibition	4.96	pIC50
CCG-203920	Inhibition	4.44	pIC50
RGS4 inhibitor 11b	Inhibition	4.08	pIC50

Binding affinities (BindingDB)

59 measured of 184 human assays (196 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2E)-3-(2-chloroanilino)-2-(3,3-dimethyl-2,4-dihydroisoquinolin-1-ylidene)-3-keto-propionic acid ethyl ester	EC50	10 nM
(3R)-2-(4-fluorophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline-3-carboxylic acid	EC50	10 nM
2,4-dimethyl-6-[2-oxidanylidene-2-(4-phenylpiperazin-1-yl)ethyl]-1,6-naphthyridin-5-one	EC50	18 nM
MLS000093573	IC50	23 nM
1-(1-adamantyl)-3-(1,3-benzodioxol-5-ylmethyl)urea	EC50	60 nM
2,5-bis(chloranyl)-3-(4-methylpiperazin-1-yl)-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	160 nM
2,5-bis(chloranyl)-3-[2-(dimethylamino)-1,3-thiazol-5-yl]-6-pyrrolidin-1-yl-cyclohexa-2,5-diene-1,4-dione	EC50	210 nM
MLS000114722	EC50	820 nM
MLS000689390	EC50	880 nM
3-chloranyl-N-(3-morpholin-4-ylpropyl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	950 nM
3,4,5-trihydroxybenzoic acid [(3R,4S,5S,6S)-3,4,5,6-tetragalloyloxytetrahydropyran-2-yl]methyl ester	EC50	951 nM
2-[2-oxidanylidene-2-[2-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]hydrazinyl]ethoxy]-N’’-[(Z)-(3-oxidanyl-4-oxidanylidene-cyclohexa-2,5-dien-1-ylidene)methyl]benzohydrazide	IC50	1070 nM
1,6,6-triphenyl-3-(p-tolyl)-3-azabicyclo[3.1.0]hexane-2,4-quinone	EC50	1160 nM
2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)sulfanyl]-1-oxidopyridin-1-ium	EC50	1320 nM
cid_25227363	EC50	1430 nM
Chebulinic acid	IC50	1520 nM
MLS000697664	IC50	1560 nM
4-chloranyl-6-(4,6-dimethylpyrimidin-2-yl)sulfanyl-N-methyl-1,3,5-triazin-2-amine	EC50	1630 nM
2-(4,6-dimethyl-3-oxidanylidene-[1,2]thiazolo[5,4-b]pyridin-2-yl)-N-(3-fluorophenyl)ethanamide	EC50	1720 nM
2-(3-keto-4,6-dimethyl-isothiazolo[5,4-b]pyridin-2-yl)-N-propyl-acetamide	EC50	1750 nM
MLS000689393	EC50	1750 nM
DEFEROXAMINE	EC50	1850 nM
1,12,23-trihydroxy-1,6,12,17,23,28-hexazacyclotritriacontane-2,5,13,16,24,27-hexone	EC50	2240 nM
2,5-bis(chloranyl)-3-piperidin-1-yl-6-(2-piperidin-1-yl-1,3-thiazol-5-yl)cyclohexa-2,5-diene-1,4-dione	EC50	2320 nM
3-chloranyl-N-(3,3-dimethylbutan-2-yl)-6-nitro-1-benzothiophene-2-carboxamide	EC50	2470 nM
MLS000544577	IC50	2630 nM
(4E)-2,3-dihydroxy-4-[[(4-methyl-2-methylimino-1,3-thiazol-3-yl)amino]methylidene]cyclohexa-2,5-dien-1-one	IC50	2720 nM
4-[(4-fluorophenyl)methyl]-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	IC50	3500 nM	US-8865750: Small molecule inhibitors of RGS proteins
MLS000759648	IC50	3520 nM
5-acetyl-2-[[5-(4-ketocyclohexa-2,5-dien-1-ylidene)-3-isoxazoline-3-carbonyl]amino]-4-methyl-thiophene-3-carboxylic acid ethyl ester	IC50	3690 nM
MLS000757112	IC50	4290 nM
(1R,19R,21S,22R,23R)-6,7,8,11,12,13,22,23-octahydroxy-3,16-dioxo-2,17,20-trioxatetracyclo[17.3.1.0^{4,9}.0^{10,15}]tricosa-4(9),5,7,10,12,14-hexaen-21-yl 3,4,5-trihydroxybenzoate	IC50	4480 nM
3-[[[(E)-(2,3-dihydroxy-4-keto-cyclohexa-2,5-dien-1-ylidene)methyl]amino]carbamoyl]-N,N-diethyl-benzenesulfonamide	EC50	5130 nM
MLS000390238	EC50	5260 nM
2-(4-Methoxy-phenyl)-[1,4]benzoquinone	IC50	5430 nM
3,4,5-trihydroxy-N’-[(1Z)-1-(4-nitrophenyl)ethylidene]benzohydrazide	EC50	5960 nM
4-[(3-carbamoyl-4,5-dimethyl-2-thienyl)amino]-4-keto-butyric acid methyl ester	EC50	6560 nM
(2Z)-3-ethyl-2-[(2E,4E)-5-(3-ethyl-1,3-benzothiazol-3-ium-2-yl)penta-2,4-dienylidene]-1,3-benzothiazole;iodide	EC50	6670 nM
(E)-3-(2-furanyl)-N-[(4-sulfamoylphenyl)methyl]-2-propenamide	EC50	7670 nM
4-(2-methylphenyl)-3-pyridin-4-yl-1H-1,2,4-triazole-5-thione	EC50	7760 nM
(4E)-5-methyl-4-[[3-[[(Z)-(3-methyl-1-phenyl-5-sulfanylidene-4-pyrazolylidene)methyl]amino]propylamino]methylidene]-2-phenyl-3-pyrazolethione	EC50	8790 nM
MLS000553854	EC50	11700 nM
4-[5-[(2,2-dimethyl-4,6-dioxo-1,3-dioxan-5-ylidene)methyl]-2-furanyl]benzenesulfonamide	EC50	11900 nM
3-(3-keto-1,2-benzothiazol-2-yl)-N,N-dimethyl-benzenesulfonamide	IC50	13000 nM
1-[3-(4-nitrophenyl)-5,6-dihydroimidazo[2,1-b][1,3]thiazol-7-ium-7-yl]ethanone;bromide	EC50	13500 nM
(2Z)-3-ethyl-2-[(E)-3-(3-ethyl-1,3-benzothiazol-3-ium-2-yl)-2-methyl-prop-2-enylidene]-1,3-benzothiazole;iodide	EC50	22400 nM
(2Z,4S,6S,12aS)-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-2-[hydroxy-(1-pyrrolidinylmethylamino)methylidene]-6-methyl-4,4a,5,5a-tetrahydrotetracene-1,3,12-trione	EC50	23700 nM
(4E)-4-[[(2-ethylimino-4-methyl-1,3-thiazol-3-yl)amino]methylidene]-2,3-bis(oxidanyl)cyclohexa-2,5-dien-1-one	EC50	29400 nM
UNM-0000305796	EC50	30000 nM
2,4-dimethyl-6-[2-[3-methyl-4-(3-methylphenyl)piperazin-1-yl]-2-oxidanylidene-ethyl]-1,6-naphthyridin-5-one	EC50	30000 nM

ChEMBL bioactivities

10 potent at pChembl≥5 of 36 total, top 10 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.28	IC50	5200	nM	CHEMBL2037237
5.25	IC50	5600	nM	CHEMBL2037236
5.21	IC50	6200	nM	CHEMBL2037227
5.15	IC50	7100	nM	CHEMBL2037232
5.12	IC50	7600	nM	CHEMBL2037228
5.12	IC50	7500	nM	CHEMBL2037235
5.11	IC50	7700	nM	CHEMBL2037365
5.08	IC50	8400	nM	CHEMBL2037358
5.02	IC50	9500	nM	CHEMBL2037362
5.00	IC50	9900	nM	CHEMBL2037354

PubChem BioAssay actives

10 with measured affinity, of 45 total; 10 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-benzyl-2-(4-chlorophenyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	5.2000	uM
4-benzyl-2-phenyl-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	5.6000	uM
4-[(4-fluorophenyl)methyl]-2-phenyl-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	6.2000	uM
4-[(4-fluorophenyl)methyl]-2-(3-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	7.1000	uM
4-benzyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	7.5000	uM
2-(4-chlorophenyl)-4-[(4-fluorophenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	7.6000	uM
2-(4-methylphenyl)-4-(2-methylpropyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	7.7000	uM
4-methyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	8.4000	uM
4-butyl-2-(4-methylphenyl)-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	9.5000	uM
2-(4-methylphenyl)-4-[(3-methylphenyl)methyl]-1,2,4-thiadiazolidine-3,5-dione	663947: Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	ic50	9.9000	uM

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aflatoxin B2	increases methylation	1
Arsenic	affects methylation	1
Diethylhexyl Phthalate	decreases expression	1
Niclosamide	decreases expression	1
Silicon Dioxide	decreases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	affects methylation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2039223	Binding	Inhibition of RGS8 interaction with Galpha0 protein by flow cytometry protein interaction assay	Small Molecule Inhibitors of Regulator of G Protein Signalling (RGS) Proteins. — ACS Med Chem Lett

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.