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Selectivity data for probe GSK778


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GSK778


Compound concentration: 10 µM
Receptor HGNC target name Inhibition [%] (Primary experimental value) Ki [nM] (Secondary experimental value) pKi
Beta1 ADRB1 4.82
Beta3 ADRB3 10.53
GABAA/BZP 91.62 1970.29 average (n=2) 5.75
GABAA 52.72 1595.89 average (n=2) 5.81
GABA/PBR 7.75
D4 DRD4 79.54 856.99 average (n=2) 6.09
D5 DRD5 31.66
DAT SLC6A3 27.90
H4 HRH4 29.26
KOR OPRK1 15.54
MOR OPRM1 16.87
NET SLC6A2 34.50
Alpha1A ADRA1A 0.31
Alpha1B ADRA1B 4.20
Alpha1D ADRA1D 17.03
Alpha2A ADRA2A 9.95
Alpha2B ADRA2B -13.60
Alpha2C ADRA2C 15.35
M1 CHRM1 -1.37
M2 CHRM2 4.05
M3 CHRM3 -3.35
Sigma 2 TMEM97 23.02
5-HT1A HTR1A 15.28
5-HT1B HTR1B 8.66
5-HT1D HTR1D 14.83
5-HT1E HTR1E -19.46
5-HT2A HTR2A -5.06
5-HT2B HTR2B -10.48
5-HT6 HTR6 -9.08
5-HT7A HTR7 -5.39
D1 DRD1 2.89
D2 DRD2 27.74
D3 DRD3 62.41 485.92 average (n=2) 6.39
5-HT2C HTR2C -0.02
5-HT3 HTR3A 69.83 4456.49 average (n=2) 5.35
5-HT5A HTR5A 21.48
Beta2 ADRB2 18.37
DOR OPRD1 38.45
H1 HRH1 0.33
H2 HRH2 12.29
H3 HRH3 -5.03
M4 CHRM4 15.71
M5 CHRM5 24.55
SERT SLC6A4 10.71
Sigma 1 SIGMAR1 38.49

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GSK778

A panel of bromodomain containing proteins (BCP) was screened in a dose-response format in duplicate.

Conclusion: Clean panel. GSK778 displayed selective binding within the BET family and over 100-fold selectivity for BRD4 BD1 over BRD4 BD2.

Target protein HGNC name Species Kd [nM]
ATAD2A ATAD2 Homo sapiens > 30000.0
ATAD2B ATAD2B Homo sapiens 25000.0
BAZ2A BAZ2A Homo sapiens > 30000.0
BAZ2B BAZ2B Homo sapiens > 30000.0
BRD1 BRD1 Homo sapiens > 30000.0
BRD2(1) BRD2 Homo sapiens 13.0
BRD2(2) BRD2 Homo sapiens 840.0
BRD3(1) BRD3 Homo sapiens 5.0
BRD3(2) BRD3 Homo sapiens 310.0
BRD4(1) BRD4 Homo sapiens 5.9
BRD4(1,2) BRD4 Homo sapiens 100.0
BRD4(2) BRD4 Homo sapiens 670.0
BRD4(FULL-LENGTH,SHORT-ISO.) BRD4 Homo sapiens 11.0
BRD7 BRD7 Homo sapiens > 30000.0
BRD9 BRD9 Homo sapiens > 30000.0
BRDT(1) BRDT Homo sapiens 18.0
BRDT(2) BRDT Homo sapiens 5400.0
BRPF1 BRPF1 Homo sapiens 15000.0
BRPF3 BRPF3 Homo sapiens > 30000.0
CECR2 CECR2 Homo sapiens > 30000.0
CREBBP CREBBP Homo sapiens 3800.0
EP300 EP300 Homo sapiens 5700.0
FALZ BPTF Homo sapiens > 30000.0
GCN5L2 KAT2A Homo sapiens > 30000.0
PBRM1(2) PBRM1 Homo sapiens 29000.0
PBRM1(5) PBRM1 Homo sapiens > 30000.0
PCAF KAT2B Homo sapiens 33000.0
SMARCA2 SMARCA2 Homo sapiens > 30000.0
TAF1(2) TAF1 Homo sapiens > 30000.0
TAF1L(2) TAF1L Homo sapiens > 30000.0
TRIM24(BROMO.) TRIM24 Homo sapiens > 30000.0
TRIM24(PHD,Bromo.) TRIM24 Homo sapiens > 30000.0
TRIM33(PHD,Bromo.) TRIM33 Homo sapiens > 30000.0
WDR9(2) BRWD1 Homo sapiens > 30000.0
 

GSK778

Shown are supplementary data from PMID: 32787145.

Conclusion: Clean panel

Target protein HGNC name Species Value Mode of action Assay Source
5-HT Transporter (SERT) SLC6A4 Homo sapiens pIC50 = 4.4 Binding SPA BacMam
5-HT1B HTR1B Homo sapiens pEC50 < 4.0 Agonist 10 µL GTPγS LEADseeker
5-HT1B HTR1B Homo sapiens pIC50 < 4.0 Antagonist 10 µL GTPγS LEADseeker
5-HT2A HTR2A Homo sapiens pEC50 < 4.6 Agonist Luminescence HEK
5-HT2A HTR2A Homo sapiens pIC50 < 4.6 Antagonist Luminescence HEK
5-HT2C HTR2C Homo sapiens pEC50 < 4.6 Agonist Luminescence CHO
5-HT2C HTR2C Homo sapiens pIC50 < 4.6 Antagonist Luminescence CHO
5HT3 HTR3A Homo sapiens pEC50 < 4.3 Agonist FLIPR
Acetylcholinesterase (AChE) ACHE Homo sapiens pIC50 = 4.2 RapidFire Mass Spec
Adenosine A2a ADORA2A Homo sapiens pEC50 < 4.0 Agonist LANCE TR-FRET Whole cell
Adrenergic Alpha 1B ADRA1B Homo sapiens pIC50 < 4.6 Antagonist Intracell Ca
Alpha 1 nAChR CHRNA1 Homo sapiens pEC50 < 4.3 Agonist FLIPR HEK293
Alpha 1 nAChR CHRNA1 Homo sapiens pIC50 = 6.0 Antagonist FLIPR HEK293
Alpha 2C Adrenoceptor ADRA2C Homo sapiens pEC50 < 4.0 LANCE TR-FRET CHO-K1
Aurora B/INCENP AURKB Homo sapiens pIC50 < 4.5 30 min IMAP 2 µM ATP
Beta2 Adrenoceptor ADRB2 Homo sapiens pEC50 < 4.0 Agonist TR-FRET
Beta2 Adrenoceptor ADRB2 Homo sapiens pIC50 < 4.0 Antagonist TR-FRET
Cannabinoid CB2 Receptor CNR2 Homo sapiens pEC50 < 4.0 Agonist FDGlu Yeast
Cyclooxygenase 2 (COX-2) PTGS2 Homo sapiens pIC50 < 4.0 FLINT
Cytochrome P450 3A4 CYP3A4 Homo sapiens pIC50 = 5.2 Vivid Green FLINT
Cytochrome P450 3A4 CYP3A4 Homo sapiens pIC50 = 6.0 Vivid Red FLINT
Dopamine 2 (D2) DRD2 Homo sapiens pIC50 = 5.5 Antagonist GTPγS SPA
Dopamine D1 DRD1 Homo sapiens pIC50 < 4.0 Antagonist LANCE TR-FRET
Dopamine D2 DRD2 Homo sapiens pEC50 < 4.0 Agonist Low Na GTPγS SPA HEK293F
Histamine Receptor H1 (HRH1) HRH1 Homo sapiens pIC50 < 4.6 Antagonist Luminescence
5HT3 HTR3A Homo sapiens pIC50 < 4.3 Antagonist FLIPR
CaV1.2 (L-type) Calcium Channel CACNA1C Homo sapiens pIC50 < 4.0 Barracuda Ephys
Monoamine Oxidase (MAO) B Inhibitor MAOB Homo sapiens pIC50 = 4.1 FLINT
KCNH2 (hERG) KCNH2 Homo sapiens pIC50 = 4.4 Antagonist Barracuda Ephys PPC
KCNQ1/KCNE1 (Kv7.1/MinK) KCNQ1
KCNE1
Homo sapiens pIC50 < 4.6 Blocker Electrophys CHO
Kv1.5 (KCNA5) KCNA5 Homo sapiens pIC50 < 4.3 Blocker Electrophys CHO
LCK LCK Homo sapiens pIC50 < 4.5 IMAP
M1 (CHRM1) CHRM1 Homo sapiens pEC50 < 4.3 Agonist Intracellular Ca Fluorescence CHO
M1 (CHRM1) CHRM1 Homo sapiens pIC50 < 4.3 Antagonist Intracellular Ca Fluorescence CHO
M2 (CHRM2) CHRM2 Homo sapiens pEC50 < 4.3 Agonist Intracellular Ca Fluorescence CHO
M2 (CHRM2) CHRM2 Homo sapiens pIC50 = 5.0 Antagonist Intracellular Ca Fluorescence CHO
NaV1.5 SCN5A Homo sapiens pIC50 = 4.3 Blocker IonWorks Electrophys 2 Hz HEK
NK1 TACR1 Homo sapiens pIC50 < 4.6 Antagonist Aequorin Luminescence U2OS
Noradrenaline Transporter (NET) SLC6A2 Homo sapiens pIC50 = 4.7 Binding SPA BacMam
NR2B (NR1A/2B) Subunit GRIN2B Homo sapiens pIC50 < 4.3 Antagonist FLIPR U2OS
OPRK1 OPRK1 Homo sapiens pEC50 < 4.0 Agonist GTPγS LEADseeker BacMam
OPRK1 OPRK1 Homo sapiens pIC50 < 4.0 Antagonist GTPγS LEADseeker BacMam
OPRM1 OPRM1 Homo sapiens pEC50 < 4.0 Agonist GTPγS LEADseeker BacMam
Organic Anion Transport Polypeptide C OATP1B1 SLCO1B1 pIC50 = 4.4 Image HEK
PDE4B PDE4B Homo sapiens pIC50 = 4.4 Luminescence
Phosphodiesterase 3A (PDE3A) PDE3A pIC50 < 4.0 Inhibition [3H]-cAMP SPA [3H]-cAMP
Phospholipidosis induction pMEC < 4.0 FLINT Fluorescence HepG2
PI3K-gamma PIK3CG Homo sapiens pIC50 < 4.5 Inhibition TR-FRET
PXR (NR1I2) NR1I2 Homo sapiens pEC50 < 4.3 Agonist FuGENE 25 µL HepG2
Vasopressin V1a AVPR1A Homo sapiens pIC50 < 4.3 Antagonist Double wash FLIPR