Table 1. MALT1 potency and selectivity profile across 156 common pharmacological targets (human unless otherwise stated) of mepazine, and tool Compounds 2 and 3, (data from Eurofins [26]), n.t. = not tested, pIC50 = negative logarithm of the concentration of compound that produce 50% inhibition/antagonism of the named target, pEC50 = negative logarithm of the concentration of the named compound that produces half the maximal agonistic effect of the named target protein.

Target Assay	Mepazine	Cpd 2	Cpd 3
	Cpd 1
MALT1 FRET pIC50	5.9	6.9	8.5
a1B pIC50	>8.0	<4.0	<4.0
H1 pIC50	>8.0	<4.0	<4.5
Sigma1 pIC50	>8.0	<4.0	<4.0
H1 Antagonist pIC50	7.9	4.5	n.t.
M5 pIC50	7.4	<4.0	<4.0
M1 IC50	7.4	<4.0	<4.0
a1A binding pIC50	7.3	<4.0	4.2
M1 Antagonist pIC50	7.0	4.8	n.t.
a1A Antagonist pIC50	6.9	4.3	<4.0
a1B Antagonist pIC50	6.8	<4.0	<4.5
M2 Binding pIC50	6.4	4.1	<4.0
D3 pIC50	6.2	<4.0	<4.0
a2C pIC50	6.1	<4.0	<4.0
5HT2B Binding pIC50	6.1	4.8	5.5
Ca2+ channel L-verapamil site Rat binding pIC50	6.1	<4.0	<4.0
NET Hu Bind pIC50	5.9	<4.0	<4.0
5-HT2C pIC50	5.9	<4.0	<4.0
5HT3 pIC50	5.8	<4.0	<4.0
5HT7 agonist pIC50	5.8	<4.0	<4.0
D2 pIC50	5.7	<4.0	<4.0
OPRk1 pIC50	5.7	<4.0	<4.0
M2 Antagonist pIC50	5.7	<4.0	<4.5
5-HT2C agonist pEC50	5.7	<4.0	<4.0
5HT1B Rat Bind pIC50	5.6	4.7	<4.0
SST4 Hu Bind pIC50	5.6	<4.0	<4.0
DOP2 Antagonist pIC50	5.3	<4.5	n.t.
AT pIC50	<4.0	5.3	4.8
A1 bind pIC50	<4.0	5.3	5.7
OPRm1 Hu Bind pIC50	5.2	<4.0	4.5
CaV-L pIC50	5.2	4.1	<4.0
A1 Agonist pEC50	5.2	<4.5	<4.5
EtA Agonist pEC50	5.1	<4.0	n.t.
5HT2B Antagonist pIC50	5.0	5.0	<4.0
D1 bind pIC50	5.0	4.0	<4.0
NaV1.5 pIC50	4.9	<4.5	<4.5
OPRk1 Agonist pEC50	4.9	<4.0	n.t.
A2A bind pIC50	4.9	<4.0	<4.0
A2A pIC50	<4.0	4.9	n.t.
OPRm1 Hu CHO cAMP TRF Agonist CR) pEC50	4.8	<4.0	<5.0
H2 pIC50	4.8	<4.0	<4.0
Ghre Agonist pEC50	4.7	<4.0	n.t.
NK1 pIC50	4.7	<4.0	<4.1
5-HT1D pIC50	4.7	<4.0	<4.0
NK1 Antagonist pIC50	4.7	4.2	n.t.
SST4 Agonist pEC50	4.6	<4.0	n.t.
β2 pIC50	4.6	<4.0	<4.0
D2 Antagonist pIC50	4.6	<4.5	n.t.
DAT bind pIC50	4.6	<4.0	<4.0
A2C Antagonist pIC50	4.5	<4.0	n.t.
M1 Agonist pEC50 DOP2 pIC50	4.5	<4.0	n.t.
A2A Antagonist pIC50	4.5	<4.5	<4.5
5-HT1A pIC50	4.5	<4.0	<4.0
Kv4.3 pIC50	4.1	4.5	<4.5
Ang2 AT1 pIC50	<5.0	4.5	n.t.
5HT4 pIC50	4.3	4.5	<4.0
5-HT7 Antagonist pIC50	4.4	<4.0	<4.0
Ang2 AT1 Agonist pEC50	4.4	<4.0	n.t.
Ghre pIC50	4.4	4.0	<4.6
MAO-B pIC50	4.4	<4.0	n.t.
MR2 pIC50	4.4	<4.0	<4.0
SET pIC50	4.4	4.0	<4.0
5-HT2C Antagonist pIC50	<4.0	4.3	<4.0
NAchA7 Bind pIC50	4.3	<4.0	<4.0
A2C Agonist pEC50	4.3	<4.0	n.t.
Hu HepG2 Tox pGlucose IC50	4.3	<3.6	<3.6
THP1 pIC50 Cytotox	4.3	<3.6	<3.6
GR pIC50	4.3	<4.0	<4.0
NK1 Agonist pEC50	4.3	<4.0	n.t.
β1 pIC50	4.3	<4.0	<4.5
PPARγ pIC50	4.2	<4.0	<4.0
BK2 Agonist pEC50	4.2	<4.0	n.t.
CB1 bind pIC50	4.2	<4.0	<4.0
NMDA pcp binding site rat binding pIC50 a1A Agonist pEC50 TRKA pIC50β1 bind pIC50	4.1	<4.0	<4.0
D3 Agonist pEC50	<4.0	4.1	<4.0
MAP3K7 pIC50	4.0	4.0	4.0
Hu HepG2 Tox Lumin pGalactose IC50	4.0	3.7	<3.6
H1 Agonist pEC50 COX1 pIC50	4.0	<4.0	n.t.
Choride ion channel–GABA gated Rat Bind pIC50	<4.0	4.0	5.5
Ghrehlin Antagonist pIC50	<5.5	<5.5	n.t.
BK2 Antagonist pIC50	<5.5	<4.0	n.t.
5-HT1D Agonist pEC50 5-HT1D Antagonist pIC50 D2 Agonist GABAB Agonist pEC50 GABAB Antagonist pIC50pEC50 DOP2 Agonist pEC505-HT1A Agonist pEC505-HT1A Antagonist pIC50	<4.5	<4.5	n.t.
β2 Antagonist pIC50	<4.5	<4.0	n.t.
TXA2 pIC50	<4.0	4.2	<4.0
ACHE pIC50	<4.0	<4.0	<4.5
A2A Agonist pEC50 5HT1B Agonist pEC50	<4.5	<4.5	<4.5
β1 Agonist pEC50 M2 Agonist pEC50	<4.0	<4.0	<5.0
5HT1B Antagonist pIC50	<4.5	<4.5	<5.5
IKs pIC50	<3.8	<4.5	<4.5
CB1 Agonist pEC50 CB1 Antagonist pIC50 D1 Agonist pEC50 D1 antagonist pIC50 OPRm1 Hu CHO cAMP TRF Antagonist CR) pIC50 MMP2 pIC50	<4.0	<4.0	<4.5
ECE1 pIC50 COX2 pIC50 SST4 Antagonist pIC50 MR2 Agonist pEC50 MR2 Antagonist pIC50 eNOS pIC50 OPRk1 Antagonist pIC50β2 Agonist pEC50 A2A Agonist pEC50 A2A Antagonist pIC50 PI3Kα pIC505HT4 Agonist pEC50; 5HT4 Antagonist pIC50	<4.0	<4.0	n.t.
ALK4 pIC50; Ang2 AT1 pIC50; CatS Hu pIC50; NAchA4 Hu Bind) pIC50; NAchA1 Hu Bind pIC50; H2 Hu CHO cAMP TRF Antagonist CR pIC50;5HT2B Agonist pEC50; ROCK2 pIC50 KDR pIC50; INSR pIC50; Central GABA benzodiazepine receptor Rat Bind pIC50; ROCK1 pIC50; Src pIC50 TSPO Hu pIC50; PDK1 pIC50; Glycine receptor strychnine sensitive agonist site rat binding pIC50; NMDA Rat Bind pIC50;RARα pIC50 MAP3K7 pIC50; GSK3β pIC50; BK2 pIC50; H2 Agonist pEC50; EtA pIC50;AurKA pIC50; D3 Antagonist pIC50; PDE6 pIC50; FGFR pIC50; CatS pIC50; cKIT pIC50 Na+/K+ ATPase pIC50; GABA α1β2γ2 pIC50; 5-HT7 Agonist pEC50; a1B Agonist pEC50; EGFRK pIC50	<4.0	<4.0	<4.0