[Preprint]. 2024 Mar 13:2023.12.20.572662. Originally published 2023 Dec 21. [Version 2] doi: 10.1101/2023.12.20.572662

Extended Data Table 3.

Fit parameters from calcium mobilization and BRET assays for the top agonists from both docking sets against the 5-HT2A (top), 5-HT2B (middle), and 5-HT2C (bottom) receptor.

	5-HT2A
	Calcium mobilization		Gαq dissociation		β-arrestin2 recruitment		Apparent Bias Factor	Apparent Bias for
Compound	pEC50	Emax	pEC50	Emax	pEC50	Emax	Apparent Bias Factor	Apparent Bias for	Model
5-HT (reference)	9.04 ± .0022	99.96 ± 0.64	8.18 ± 0.07	100.31 ± 2.45	7.78 ± 0.063	99.80 ± 2.34	1.0	-	-
Z5247692629	6.61 ± 0.030	89.52 ± 1.21	6.15 ± 0.11	95.63 ± 5.59	5.48 ± 0.14	79.32 ± 8.00	2.2	Gq	cryoEM
Z2876442907	6.19 ± 0.028	95.75 ± 1.37	5.80 ± 0.11	92.56 ± 6.63	5.41 ± 0.19	64.78 ± 9.55	1.4	Gq	cryoEM
Z5247692566	5.52 ± 0.036	78.45 ± 1.87	5.53 ± 0.31	73.4 ± 16.73	N.D.	N.D.	N.D.	N.D.	cryoEM
Z1612290114	5.94 ± 0.109	22.99 ± 1.37	6.03 ± 0.12	48.12 ± 3.22	5.31 ± 0.15	118.83 ± 15.27	0.8	βarr2	cryoEM
Z2825713589	6.92 ± 0.022	97.99 ± 0.88	6.08 ± 0.11	101.16 ± 5.99	5.40 ± 0.09	102.39 ± 7.42	1.8	Gq	AF2
Z4154032166	7.10 ± 0.029	91.96 ± 1.05	6.56 ± 0.11	97.68 ± 4.81	5.94 ± 0.07	75.77 ± 3.31	2.1	Gq	AF2
WXVL_BT0793LQ2118	7.38 ± 0.079	62.92 ± 1.86	6.81 ± 0.12	80.64 ± 4.13	6.50 ± 0.10	44.60 ± 2.06	1.4	Gq	AF2
Z3517967757	5.81 ± 0.031	85.64 ± 1.50	5.75 ± 0.15	76.30 ± 7.29	4.96 ± 0.67	69.34 ± 57.84	2.6	Gq	AF2
Z3881312504	7.23 ± 0.047	50.33 ± 0.92	6.89 ± 0.16	68.84 ± 4.82	6.41 ± 0.20	35.20 ± 3.39	2.3	Gq	AF2

	5-HT2B
	Calcium mobilization		Gαq dissociation		β-arrestin2 recruitment		Apparent Bias Factor	Apparent Bias for
Compound	pEC50	Emax	pEC50	Emax	pEC50	Emax	Apparent Bias Factor	Apparent Bias for	Model
5-HT (reference)	8.95 ± 0.021	99.95 ± 0.64	9.19 ± 0.12	99.64 ± 3.52	8.96 ± 0.11	99.37 ± 3.55	1.0	-	-
Z5247692629	6.80 ± 0.028	75.74 ± 0.91	6.94 ± 0.13	153.94 ± 8.71	6.32 ± 0.17	102.79 ± 8.95	3.6	Gq	cryoEM
Z2876442907	5.92 ± 0.037	88.63 ± 1.82	5.95 ± 0.25	156.65 ± 23.55	5.68 ± 0.21	93.74 ± 13.54	1.8	Gq	cryoEM
Z5247692566	5.58 ± 0.025	76.72 ± 1.24	5.82 ± 0.18	138.61 ± 15.80	5.23 ± 0.24	116.14 ± 26.32	2.7	Gq	cryoEM
Z1612290114	5.02 ± 0.219	12.10 ± 2.36	N.D.	N.D.	5.09 ± 0.21	104.93 ± 23.59	N.D.	N.D.	cryoEM
Z2825713589	7.09 ± 0.021	94.14 ± 0.79	6.85 ± 0.12	172.53 ± 8.9	6.53 ± 0.15	112.35 ± 7.87	1.9	Gq	AF2
Z4154032166	6.60 ± 0.06	50.86 ± 1.37	6.67 ± 0.21	98.24 ± 9.36	6.15 ± 0.31	71.07 ± 12.21	2.7	Gq	AF2
WXVL_BT0793LQ2118	N.D.	N.D.	7.71 ± 0.77	29.82 ± 8.45	7.41 ± 0.65	28.97 ± 7.20	1.2	Gq	AF2
Z3517967757	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	AF2
Z3881312504	N.D.	N.D.	6.78 ± 0.94	24.54 ± 10.48	5.77 ± 0.30	50.33 ± 10.01	2.9	Gq	AF2

	5-HT2C
	Calcium mobilization		Gαq dissociation		β-arrestin2 recruitment		Apparent Bias Factor	Apparent Bias for
Compound	pEC50	Emax	pEC50	Emax	pEC50	Emax	Apparent Bias Factor	Apparent Bias for	Model
5-HT (reference)	9.10 ± 0.041	99.80 ± 1.21	8.30 ± 0.07	100.40 ± 2.23	8.37 ± 0.14	99.21 ± 4.48	1.0	-	-
Z5247692629	5.90 ± 0.083	76.61 ± 3.57	6.08 ± 0.26	80.03 ± 11.94	5.55 ± 0.30	73.81 ± 15.67	4.2	Gq	cryoEM
Z2876442907	6.20 ± 0.054	98.70 ± 2.66	5.98 ± 0.22	94.28 ± 12.48	5.74 ± 0.13	93.02 ± 8.14	2.0	Gq	cryoEM
Z5247692566	5.36 ± 0.331	10.26 ± 2.44	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	cryoEM
Z1612290114	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	cryoEM
Z2825713589	5.39 ± 0.09	96.11 ± 5.66	5.43 ± 0.29	78.47 ± 17.50	N.D.	N.D.	N.D.	N.D.	AF2
Z4154032166	7.02 ± 0.07	89.53 ± 2.38	6.7 ± 0.11	102.53 ± 4.96	6.46 ± 0.19	72.61 ± 6.64	2.8	Gq	AF2
WXVL_BT0793LQ2118	N.D.	N.D.	6.27 ± 0.33	49.37 ± 8.54	6.01 ± 0.48	22.49 ± 6.56	4.7	Gq	AF2
Z3517967757	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.	AF2
Z3881312504	N.D.	N.D.	8.56 ± 1.19	29.95 ± 11.26	N.D.	N.D.	N.D.	N.D.	AF2