upporting information IDETIICATI VEL ERTI TRAPRTER CMPUD BY VIRTUAL CREEIG Mari Gabrielsen, Rafał Kurczab, Agata iwek, Małgorzata Wolak, Aina W. Ravna,Kurt Kristiansen,Irina Kufareva, Ruben Abagyan, Gabriel owak, Zdzisław Chilmonczyk, Ingebrigt ylte and Andrzej J. Bojarski igure 1. Additional 3D ligand-based pharmacophore models igure 2. pectral data igure 3. Radioligand binding curves Table 1. Reference ligands Table 2. Metrics-threshold optimisation details Table 3. ummary, in vitro screening Table 4. ummary, in vitro full binding assays Pages 2 3 Pages 4 6 Pages 7 9 Pages 11-12 Page 13 Pages 14 19 Pages 20 27 1
igure 1. 3D ligand-based pharmacophore models. ne reference ligand from each class is mapped. Blue sphere: hydrophobic feature; range sphere: aromatic feature; Red sphere: positive ionisable feature; Green sphere: hydrogen bond acceptor feature; Magenta sphere: hydrogen bond donor feature. RI/RI TCA Mazindol 3-Phenyltropane Radioligand luvoxamine 2
()-Citalopram ertraline luoxetine/venlafaxine 3
igure 2. pectral data for the most active representative of clusters C01 C16 as supported by vendors (Asinex, ChemBridge, ChemDiv, Enamine, Life Chemicals) see Table 3. C01 A13153175 C02 T5544147 R317282 K R317282 Dovbiy C121422 289.22 PPM 1.72 0.86 0.81 1.00 0.14 2.00 PPM 2.58 1.24 1.18 3.03 0.86 0.81 1.00 8.2 8.0 7.8 7.6 7.4 ile name: R317282 Date: 07-ov-2005 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 perator:reutova olvent: : 399.9601 Mz W: 7199 z C: 0 TE: 303 K PW: 7.50 usec, RG: 48 AQ: 2.00 sec, RD: 0.00 sec I: 65536 *R317282* C03 5417988 C04 T6125232 C05 46524932 C06 9066608 4
C07 5458751 C08 BA12193322 C09 C466-0145 C10 T6406455 C11 T6574432 C12 T0502-9459 2935255 2935255 C18203 313.37 1.03 2.07 PPM 2.06 PPM 1.02 1.03 1.00 3.07 1.05 1.05 1.04 5.96 1.03 2.07 2.06 1.02 1.03 7.4 7.2 7.0 6.8 6.6 6.4 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 ile name: 2935255 Klishin : 399.9703 Mz C: 0 PW: 7.50 usec, RG: 30 I: 65536 Date: 02-ov-2009 olvent: DM-d6 + C4 W: 6803 z TE: 293 K AQ: 1.33 sec, RD: 0.00 sec 5
C13 E300-08612 C14 2147-0594 R320942 K R320942 Dovbiy C181822 333.26 PPM 7.6 7.4 7.2 7.0 6.8 6.6 6.4 0.86 0.71 0.40 0.25 1.00 2.07 0.99 2.01 1.00 0.89 1.73 1.19 2.79 PPM 0.17 0.67 1.00 2.07 0.99 2.01 1.00 0.89 ile name: R320942 Date: 20-Dec-2005 11.0 10.0 9.0 8.0 7.0 6.0 5.0 4.0 3.0 2.0 1.0 perator:reutova olvent: : 399.9600 Mz W: 6398 z C: 0 TE: 293 K PW: 7.00 usec, RG: 38 AQ: 1.80 sec, RD: 0.00 sec I: 65536 *R320942* C15 2189-0009 C16 BA15203752 4.87 0.98 0.98 2.00 1.02 2.02 0.81 3.00 PPM 7.345 7.309 7.297 7.296 6.942 6.934 6.930 6.921 6.839 6.833 3.750 3.724 3.292 3.290 2.950 2.928 2.784 2.754 PPM 2.507 2.502 2.498 0.992 0.978 f2189-0009 7.345 7.309 7.297 7.296 6.942 6.934 6.930 6.921 6.839 6.833 PPM 3 C PPM 4.87 0.98 0.98 7.40 7.30 7.20 7.10 7.00 6.90 6.80 K(0) 7.5 7.0 6.5 6.0 5.5 5.0 4.5 4.0 3.5 3.0 2.5 2.0 1.5 1.0 ile name: f2189-0009 Expert: A.Ryabitsky : 400.0778 Mz; sw: 8000 z; at: 1.50 sec : ; pw: 9,65 usec I: 65536, TD: 24000 Date: 04_oct_2013 olvent: DM 0928 TE: 293 K block: s11115 6
igure 3. Radioligand binding curves. Concentration-dependent inhibition of specific [ 3 ]-citalopram binding to ERT in rat neocortical tissue by the highest affinity representative of clusters C1 C16 (see Table 3) and for three reference compounds: Imipramine, Citalopram and luoxetine. Data are from the mean of two independent experiments. C01 A13153175 C02 T5544147 C03 5417988 C04 T6125232 C05 46524932 C06 9066608 7
C07 5458751 C08 BA12193322 C09 C466-0145 C10 T6406455 C11 T6574432 C12 T0502-9459 C13 E300-08612 C14 2147-0594 8
C15 2189-0009 C16 BA15203752 Imipramine, K i = 28.1 nm (EM ± 1.4) a Escitalopram, K i = 1.1 nm (EM ± 0.1) a luoxetine, K i = 14.1 nm (EM ± 1.6) a a According to M.J. wens et al. (JPET 283:1305 1322, 1997) Imipramine, Citalopram and luoxetine ERT activity, measured in similar conditions (rat cortex, [ 3 ]-citalopram), were: K i = 8.7 ± 0.04, 0.75 ± 0.002 and 2.0 ± 0.1, respectively. 9
Table 1. Reference ligands. 3-Phenyltropanes Cocaine K i = 95 nm 1 AB-248 K i = 9.88 nm 2 AB-338 K i = 118 nm 3 β-ct K i = 63 nm 4 β-cpt-tartrate K i = 178 nm 5 I RTI-31 K i = 44.5 nm 6 RTI-32 K i = 23 nm 5 RTI-55 (β-cit) K i = 55 nm 7 RTI-83 K i = 2.6 nm 8 RTI-112 K i = 0.95 nm 9 RTI-121 K i = 12.54 nm 10 I RTI-142 K i = 45nM 11 I RTI-311 K i = 30 nm 11 TCAs -1 K i = 0.58 nm 12 Amitriptyline K i = 0.88 nm 13 omipramine K i = 0.05 nm 13 Desipramine K i = 20 nm 14 Imipramine K i = 0.77 nm 15 Protriptyline K d = 19.6 nm 16 (R)-Trimipramine K d = 149 nm 16 10
Mazindols (R)-Mazindol K i = 103 nm 17 (R)-Mazindane K i = 13 nm 17 (R)-MAZ-10 K i = 82 nm 17 Br (R)-MAZ-85 K i = 413 nm 17 (R)-MAZ-89 K i = 1380 nm 17 Radioligands 2 2 2 I 2 Br 403U76 K i = 55nM 18 4-ADAM K i = 1.46 nm 19 ADAM K i = 0.01 nm 20 AM K i = 1.04 nm 19 DAPA K i = 2.23 nm 21 2 I 2 I DAB K i = 1.1 nm 22 IDAM K i = 0.09 nm 22 MADAM K i = 0.25 nm 23 DAM K i = 0.12 nm 22 RIs 2 ()-Citalopram K i = 1 nm 24 Desmethyl-()- citalopram K i = 116 nm 25 Didesmethyl-()- citalopram K i = 194 nm 26 ()-LU-08-052- K i = 14 nm 26 ()-LU-33-086- K i = 47 nm 26 2 2 (R)-luoxetine K i = 0.27 nm 13 Desmethyl-(R)- fluoxetine K i =26 nm 27 (R)-Venlafaxine K i = 3.81 nm 13 -desmethyl-(r)- venlafaxine K i = 40.2 nm 28 luvoxamine K i = 3.08 nm 29 11
ertraline K i = 0.79 nm 30 2 Desmethyl-sertraline K d = 3 nm 16 1 Bioorg. Med. Chem., 2009, 17:5126-5132 2 J. Med. Chem., 2005, 48:2758:2767 3 J. eurochem., 2008, 105: 1794-1805 4 J. Med. Chem., 2004, 47:6325:6401 5 Bioorg. Med. Chem., 2009, 17:5126-5132 6 Bioorg. Med. Chem. Lett., 2003, 13:2113-2151 7 Bioorg. Med. Chem., 2007, 15:4112-4159 8 J. Med. Chem., 2002, 45:4018-4029 9 J. Med. Chem., 2003, 46:1710-1775 10 J. Med. Chem., 1995, 38:372-379 11 JPET, 2004, 308: 679-687 12 Bioorg. Med. Chem., 2009, 17:4814-4900 13 The DrugMatrix Pharmacology data is a subset of the data freely available from the ational Toxicology Program. or more details see: https://ntp.niehs.nih.gov/drugmatrix/index.html 14 J. Med. Chem., 2010, 53:7821-7869 15 J. Med. Chem., 2011, 54:5315-5320 16 Eur. J. Pharm., 1997, 340:249-258 17 J. Biol. Chem., 1998, 273: 19459-19468 18 J. Med. Chem., 2002, 45:4621-4716 19 J. Med. Chem., 2005, 48:2557-2559 20 Bioorg. Med. Chem. Lett., 2013, 23:863-869 21 J. Med. Chem., 2002, 45:1246-1253 22 J. Med. Chem., 2004, 47:5221-5258 23 J. Med. Chem., 2005, 48:4213-4254 24 Bioorg. Med. Chem. Lett., 2010, 20:2979-2983 25 PA, 2011, 108(29):12137-12142 26 J. Biol. Chem., 2004, 279:42147-42156 27 Bioorg. Med. Chem., 2009, 17:331-337 28 J Pharmacol Exp Ther., 2006, 318(2):657-665 29 J. Med. Chem., 2000, 43:639-648 30 Br. J. Pharmacol., 2009, 158:1:1 12
Table 2. Metrics-threshold optimisation details. ptimized pair metric-thresholds for each query and type of molecular fingerprint used in 2D fingerprint-based screening. fp; fingerprint. Query Metrics (threshold) 2D pharmacophore-based fp Chemical hashed fp RIs caled Tanimoto (> 0.59) Asymmetric Euclidean (< 4.10) Mazindols Asymmetric Tanimoto (> 0.83) Asymmetric Euclidean (< 5.80) TCAs Tanimoto (> 0.75) Asymmetric Tanimoto (> 0.85) Radioligands caled Tanimoto (> 0.93) Tanimoto (> 0.80) 3-phenyltropanes Euclidean (< 15) Tanimoto (> 0.75) luvoxamine Tanimoto (> 0.65) Asymmetric Tanimoto (> 0.60) luoxetine caled Tanimoto (> 0.59) Asymmetric Tanimoto (> 0.60) ertraline caled Tanimoto (> 0.89) Tanimoto (> 0.80) ()-citalopram caled Tanimoto (> 0.85) Tanimoto (> 0.80) General query Asymmetric Euclidean (< 19.57) Asymmetric Euclidean (< 4.88) 13
Table 3. ummary, in vitro screening. Results for compounds not evaluated in full binding assays. %: per cent inhibition of [ 3 ]-citalopram in a tested compound concentration of 1.66 x 10-6 M. V, virtual screening; 2L, hit-to-lead screening; A, Asinex; CB, ChemBridge; CD, ChemDiv; E, Enamine; LC, Life Chemicals. C01 Q Q Q R () 3 n Q = C,,, n= 1, 2, 3 T6572527 E V 23% E300-15172 E V 8% T6541571 E V 0% T6563961 E V 19% T6097066 E V 12% T6391251 E V 28% 9074100 CB V 35% T5328401 E 2L 1% BA 13152952 A 2L 23% BA 13152964 A 2L 34% BA 13153014 A 2L 3% BA 13153124 A 2L 21% BA 13153220 A 2L 14% BA 13154032 A 2L 51% 5411476 CB 2L 0% 66387016 CB 2L 0% 76930976 CB 2L 0% 9008974 CB 2L 12% 9009971 CB 2L 17% 9011153 CB 2L 29% 9011938 CB 2L 23% 9033159 CB 2L 29% 9033183 CB 2L 32% 9035211 CB 2L 16% 9035461 CB 2L 13% 9036510 CB 2L 41% 9037933 CB 2L 37% 9038241 CB 2L 40% 9038263 CB 2L 0% 9040231 CB 2L 5% 9040567 CB 2L 55% 9040650 CB 2L 28% 9041293 CB 2L 0% 9041717 CB 2L 4% 9056490 CB 2L 25% C01 Q Q Q R () 3 n Q = C,,, n= 1, 2, 3 9059746 CB 2L 45% 9061169 CB 2L 37% 9061259 CB 2L 7% 9066104 CB 2L 40% 9068520 CB 2L 12% 9069953 CB 2L 21% 9070230 CB 2L 53% 9073186 CB 2L 36% 9082598 CB 2L 16% 9131149 CB 2L 12% 9141994 CB 2L 9% 9147095 CB 2L 10% T6238595 E 2L 8% T6096981 E 2L 53% T6159285 E 2L 11% T6330054 E 2L 27% T5382843 E 2L 24% T5630409 E 2L 44% T6356839 E 2L 0% E300-30593 E 2L 36% E300-33307 E 2L 55% C02 Q Q =,, A 21183507 A V 14% T5518584 E 2L 9% A 17208005 A 2L 4% T5759033 E 2L 0% T5973923 E 2L 0% T6036523 E 2L 27% T6051526 E 2L 5% T6335079 E 2L 5% T6582942 E 2L 33% 14
C03 ()n A A = C,,, n = 1, 2, 3 T6174731 E V 33% T6128946 E V 13% T6495752 E V 30% T5225319 E V 0% 5587546 E V 23% T5770360 E V 11% T5562311 E V 0% T5455271 E V 0% T5237519 E V 3% 5263235 CB 2L 0% 5266333 CB 2L 7% 5267909 CB 2L 29% 5429006 CB 2L 0% 5432071 CB 2L 0% 5591016 CB 2L 0% 5782714 CB 2L 2% 5937522 CB 2L 0% 6039093 CB 2L 0% E300-43517 E 2L 22% E300-40013 E 2L 26% E300-37492 E 2L 0% E300-40880 E 2L 26% C04 R 4 Q A () n R 3 A = C, Q =, C, n = 1, 2, 3 4138-0251 CD V 0% T5232666 E V 20% A 05124805 A 2L 0% A 17355263 A 2L 0% T5587149 E 2L 14% T5606738 E 2L 10% T6070323 E 2L 0% T6233877 E 2L 41% T6241255 E 2L 42% E300-24706 E 2L 50% T6149790 E 2L 6% C05 () n n = 0, 1 4789-4650 CD V 4% 4358-4563 CD V 0% C06 5868-0721 CD V 14% 9152206 CB V 25% 9151992 CB V 36% 9058098 CB V 18% 9031448 CB V 27% 9028799 CB V 73% 9027793 CB V 30% 7868962 CB V 4% 7727219 CB V 11% 5144057 CB V 4% 5137860 CB V 16% T5380001 E V 28% T5379992 E V 0% 9064087 CB 2L 0% 9115971 CB 2L 0% T6412799 E 2L 4% E300-51741 E 2L 0% C07 E534-0079 CD V 0% A 15030376 A 2L 17% A 15030399 A 2L 31% A 15030615 A 2L 34% A 15030947 A 2L 9% A 15398801 A 2L 31% A 16295786 A 2L 31% A 16295792 A 2L 6% A 16295793 A 2L 45% A 16295817 A 2L 31% Y 16295802 A 2L 45% R 3 15
C07 C09 Y 16295810 A 2L 46% Y 16296018 A 2L 50% C08 R 3 Q = C, () n = 0, 1, 2 n Q T5225178 E V 12% 5140-0397 CD V 0% 3220-0013 CD V 4% 6984665 CB V 5% 6761636 CB V 0% 5936292 CB V 11% E300-24349 E V 17% E300-13068 E V 17% T5376856 E V 14% T6456715 E V 28% T6456645 E V 0% E300-45550 E V 30% T6176301 E V 0% E300-15046 E V 9% 5525730 CB 2L 8% C09 C466-0454 CD V 11% C466-0432 CD V 5% C466-0389 CD V 1% C466-0384 CD V 15% C466-0362 CD V 10% C466-0338 CD V 2% C466-0331 CD V 10% C466-0315 CD V 11% C466-0301 CD V 12% C466-0299 CD V 21% C466-0296 CD V 27% C466-0132 CD V 12% C466-0035 CD V 26% C466-0005 CD V 34% C466-0140 CD 2L 19% C466-0465 CD 2L 27% C466-0429 CD 2L 18% C10 T6438366 E V 0% T6465725 E V 5% T6220912 E V 15% G500-0050 CD V 71% T5309167 E 2L 4% G500-0032 CD 2L 29% G500-0066 CD 2L 21% D232-0543 CD 2L 0% D232-0541 CD 2L 0% D232-0544 CD 2L 4% T5971089 E 2L 34% T6308479 E 2L 25% T6433904 E 2L 9% T0517-3768 E 2L 14% T5322832 E 2L 21% T5712535 E 2L 20% T5831235 E 2L 29% T5966472 E 2L 32% T5966646 E 2L 8% T5978322 E 2L 21% T5989954 E 2L 0% T5993662 E 2L 16% T5996454 E 2L 29% T6008734 E 2L 17% T6028717 E 2L 12% T6319607 E 2L 50% T6327188 E 2L 8% T5984252 E 2L 26% T6583458 E 2L 4% T6130335 E 2L 27% T5993645 E 2L 19% 16
C10 C13 R 3 T6602842 E 2L 4% 2038-0038 LC 2L 0% 2038-0056 LC 2L 11% 2038-0068 LC 2L 27% 2038-0087 LC 2L 21% 2038-0089 LC 2L 14% 2880-0040 LC 2L 16% 2880-0061 LC 2L 4% 2880-0115 LC 2L 0% 2880-0116 LC 2L 3% 5260-0487 LC 2L 25% C11 R 3 R 4 T0519-9482 E V 27% T5382975 E 2L 5% T0518-7491 E 2L 0% T6004559 E 2L 7% T6004560 E 2L 10% C12 T0502-8381 E V 19% T5558431 E V 22% T0503-0149 E V 5% 1646-0128 CD V 12% 8815166 CB V 11% 5812340 CB V 19% 5257210 CB V 13% T5475294 E 2L 1% T5485902 E 2L 3% T5558011 E 2L 16% T5638479 E 2L 5% D090-0072 CD V 4% C800-0910 CD V 7% C800-0868 CD V 15% 5264-1183 CD V 0% 5398258 CB V 16% 5224616 CB V 8% 5154514 CB V 7% 5118742 CB V 14% 5118739 CB V 3% 5118737 CB V 10% 5118736 CB V 11% 5118734 CB V 11% BA 00666661 A 2L 3% T5900131 E 2L 18% C14 Q = C, n = 0, 1 Q BA 09888845 A V 15% BA 09888851 A V 0% 1386-0111 LC V 20% 1386-0115 LC V 1% 1386-0117 LC V 33% 1386-0125 LC V 30% 8012-6939 CD V 20% 8012-6810 CD V 22% 8010-8408 CD V 34% 8010-8406 CD V 20% 5154819 CB V 2% 8878479 CB V 21% 8878184 CB V 9% 5224759 CB V 15% 5222729 CB V 14% 5118822 CB V 10% 5118821 CB V 33% 5118816 CB V 18% 5118813 CB V 11% 5118812 CB V 7% 5118810 CB V 29% () n 17
C14 Q = C, n = 0, 1 () n Q 5118806 CB V 14% C15 () n n = 0, 1 T6344296 E V 0% T6245113 E V 0% T6338677 E V 14% 4964-4708 CD V 17% 3169-1283 CD V 20% 7580633 CB V 7% 5716938 CB V 0% C17 Q Q Q Q () n Q = C, n = 0, 1 T5243125 E V 14% T5243117 E V 0% C24 R 3 T6443690 E V 11% T6505055 E V 21% 7951876 CB V 19% T5720200 E V 16% T5495832 E V 14% C25 T6491899 E V 21% T6484123 E V 29% T6466202 E V 11% C26 5647171 CB V 6% 5172501 CB V 8% C19 C27 R1 BA 03163011 A V 2% BA 0190078 A V 0% C21 () n n = 0,1 T6191766 E V 38% 5476820 CB V 17% C23 D399-2348 CD V 0% D399-2231 CD V 9% D399-1230 CD V 21% T6219537 E V 25% T6329918 E V 13% T6464711 E V 3% C28 T6213129 E V 23% T6224290 E V 17% C29 R 3 2 7956392 CB V 14% 18
C30 R 3 T5232794 E V 15% 12826903 CB V 15% 5423806 CB V 20% C31 T0514-4862 E V 15% C32 2 7921501 CB V 27% C33 T6425675 E V 0% Br C34 4333-1690 CD V 0% C35 D388-0242 CD V 6% C36 53910972 CB V 17% C37 T6330099 E V 35% 19
Table 4. ummary, in vitro full binding assays. %: per cent inhibition of [ 3 ]-citalopram in a tested compound concentration of 1.66 x 10-6 M (from screening). V, virtual screening; 2L, hit-to-lead screening; A, Asinex; CB, ChemBridge; CD, ChemDiv; E, Enamine; LC, Life Chemicals. The objective ranking of unique compounds with ICM VL score < -10 is shown. C01 tructure ID Path Vendor K i [nm] ± EM (%) Ranking A 13153175 2L A 90.5 ± 8.7 (69%) 196/740 9034414 V CB 133.6 ± 10.2 (36%) 119/740 E300-33377 2L E 155.4 ± 2.3 (59%) 259/1195 9013195 V CB 163.6 ± 17.9 (38%) 159/740 T6209417 2L E 427 ± 23.7 (20%) 331/1195 9138914 2L CB 609 ± 22.7 (44%) 189/1195 T5519701 2L E 670.3 ± 59 (39%) 311/1195 9144305 2L CB 708.8 ± 51 (26%) 167/1195 9033944 2L CB 713. ± 49 (44%) 229/1195 9134052 2L CB 824.5 ± 112.2 (31%) 196/1195 T5518872 2L E 1200 ± 100 (14%) 315/1195 9131285 V CB 1800 ± 218.6 (30%) 204/740 9063122 2L CB 2400 ± 60 (47%) 169/1195 T6423853 2L E 3000 ± 25 (1%) 249/1195 5410288 2L CB 3900 ± 200 (29%) 221/1195 Br T5855935 2L E 14000 ± 1300 (24%) 322/1195 Br T6604625 2L E >20,000 (5%) 324/1195 T6290567 2L E >20,000 (35%) 228/1195 T6109140 2L E >20,000 (57%) 325/1195 20
C02 tructure ID Path Vendor K i [nm] ± EM (%) Ranking T5544147 V E 336 ± 41.5 (46%) 568/740 T6032474 2L E 1400 ± 40 (44%) 1169/1195 BA 01354708 2L A 1600 ± 57 (5%) 35/740 4102378 2L CB >10,000 (0%) - C03 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 5417988 2L CB 926 ± 57 (33%) 932/1195 2 E300-41890 V E 998.5 ± 99.6 (33%) 509/740 5268132 2L CB 1000 ± 100 (42%) 935/1195 5348352 2L CB 1800 ± 100 (45%) 942/1195 T5611947 2L E >20,000 (22%) 100/1195 5956659 2L CB >20,000 (8%) - 5263252 2L CB >20,000 (6%) 941/1195 2 BA 09614992 2L A >20,000 (0%) 132/740 C04 tructure ID Path Vendor K i [nm] ± EM (%) Ranking T6125232 2L E 1.5 ± 0.3 (54%) 991/1195 T5376230 V E 264 ± 11.1 (42%) 524/740 T6275452 V E 288 ± 15.2 (50%) 322/740 T5492969 2L E 1000 ± 100 (46%) 1008/1195 9995-0329 V LC >10,000 (20%) 595/740 21
C05 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 46524932 V CB 152 ± 12.7 (72%) - BA 07566563 V A 1500 ± 50 (23%) 558/740 C06 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 9066608 V CB 28.4 ± 0.3 (30%) 190/740 9029307 V CB 42.5 ± 1.3 (49%) 12/740 7953237 V CB 214.4 ± 19.0 (43%) 36/740 7989485 V CB 657 ± 43.0 (29%) 163/740 Br 7866625 V CB 805.7 ± 15.2 (22%) 57/740 Br 7994461 V CB 1500 ± 27 (24%) 99/740 7859488 V CB 2000 ± 70 (22%) 192/740 9158341 V CB 2300 ± 78 (0%) 64/740 9016783 V CB 2500 ± 45 (6%) 44/740 5868-0724 V CD 3100 ± 115.5 (12%) 323/740 Br 22
C07 tructure ID Path Vendor K i [nm] ± EM (%) Ranking Br 5458751 V CB 50 ± 1.7 (52%) 203/740 5456380 V CB 84 ± 3.7 (47%) 226/740 Br Y 16295816 2L A 106.8 ± 10.7 (60%) 629/740 5421949 V CB 212.5 ± 22.7 (31%) 77/740 A 16295801 2L A 364 ± 12.6 (46%) 521/740 Y 16295876 2L A 441 ± 41.9 (56%) 455/740 Y 15401605 2L A 1100 ± 50 (38%) 466/740 A 16295838 2L A 1700 ± 60 (36%) 317/740 A 15030402 2L A 1700 ± 68 (40%) 188/740 C08 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 2 BA 12193322 2L A 22.3 ± 2.8 (35%) 350/740 7646925 2L CB 138.2 ± 1.0 (22%) 113/1195 2 7659606 V CB 321 ± 29 (47%) 51/740 2 7438550 V CB 330 ± 32.0 (34%) 8/740 2 T5654930 V E 1200 ± 57.7 (16%) 2/740 2 BA 09914758 V A >20,000 (11%) 41/740 23
C09 tructure ID Path Vendor K i [nm] ± EM (%) Ranking C466-0145 V CD 86.1 ± 8.1 (63%) 373/740 C466-0455 2L CD 1000 ± 60 (32%) 668/740 C466-0120 V CD 1100 ± 47.3 (24%) 305/740 C466-0097 2L CD >20,000 (32%) - C466-0049 2L CD >20,000 (0%) 962/1195 C10 tructure ID Path Vendor K i [nm] ± EM (%) Ranking T6406455 2L E 127 ± 4.5 (30%) 477/1195 T5777260 2L E 129 ± 9.8 (47%) 455/1195 T5527243 2L E 262.8 ± 15.5 (60%) 891/1195 Br 2038-0058 2L LC 305.2 ± 3.2 (32%) 1/740 G500-0036 V CD 802 ± 67 (1%) 20/740 Br T5323096 2L E 1200 ± 50 (41%) 335/1195 G500-0167 2L CD 1300 ± 40 (10%) 461/1195 T6256130 2L E 3500 ± 200 (38%) 572/1195 T6071079 2L E 5000 ± 441 (45%) 480/1195 D232-0537 2L CD 13,000 ± 900 (32%) 400/1195 T5998288 2L E >20,000 (17%) 913/1195 24
C11 tructure ID Path Vendor K i [nm] ± EM (%) Ranking T6574432 V E 56 ± 8.2 (45%) 100/740 C094-1557 V CD 660 ± 61.8 (26%) - C094-1552 V CD 3400 ± 300 (39%) - C12 tructure ID Path Vendor K i [nm] ± EM (%) Ranking + - T0502-9459 V E 268 ± 16 (40%) 734/740 T0503-1300 V E 790 ± 8.8 (37%) 70/740 T5858818 2L E 3700 ± 200 (30%) 182/740 C13 tructure ID Path Vendor K i [nm] ± EM (%) Ranking E300-08612 V E 322 ± 29 (39%) 288/740 T0520-2884 2L E >20,000 (28%) 377/740 C14 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 2147-0594 V LC 2300 ± 115.5 (31%) 565/740 Br 25
C15 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 2189-0009 V LC 2700 ± 200 (21%) 207/740 A 14228917 V A >20,000 (0%) 165/740 C16 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 2 BA V A 2300 ± 200 (6%) 4/740 15203752 C17 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 9995-0040 V LC >20,000 (0%) - C18 tructure ID Path Vendor K i [nm] ± EM (%) Ranking BA V A >20,000 (0%) 33/740 01376215 C19 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 0919-0520 V LC >20,000 (8%) 152/740 C20 tructure ID Path Vendor K i [nm] ± EM (%) Ranking A 09531546 V A >20,000 (1%) 71/740 26
C21 tructure ID Path Vendor K i [nm] ± EM (%) Ranking 6623-0073 V CD >20,000 (9%) 221/740 C22 tructure ID Path Vendor K i [nm] ± EM (%) Ranking E300-55368 V E >20,000 (6%) 184/740 27