NPASS Compound

Natural Product: NPC471053

Natural Product ID	NPC471053
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Symplostatin 5
IUPAC Name	sodium;[(2R)-3-[[(2S)-1-[[(2S,5S,8S,11R,12S,15Z,18S,21R)-2,5-dibenzyl-8-[(2R)-butan-2-yl]-15-ethylidene-21-hydroxy-4,11-dimethyl-3,6,9,13,16,22-hexaoxo-10-oxa-1,4,7,14,17-pentazabicyclo[16.3.1]docosan-12-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-2-methoxy-3-oxopropyl] sulfate
Synonyms	Symplostatin 5
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2338554
PubChem CID	71711730
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0001813] Peptidomimetics [CHEMONTID:0001961] Depsipeptides [CHEMONTID:0001994] Cyclic depsipeptides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 135137 0 0 0 0 0 0 0 0999 V2000 2.1888 -4.6732 0.6368 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6413 -3.2394 0.6917 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1231 -3.3589 0.6867 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.5794 -2.0489 0.7416 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9750 -2.2018 0.7323 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8356 -2.4688 -0.1290 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5133 -2.7049 -1.4409 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3041 -2.5190 0.3329 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.8516 -3.8491 0.0075 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1506 -4.9944 0.6732 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0977 -5.6486 0.0915 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4942 -6.6981 0.7470 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8836 -7.1523 1.9826 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9557 -6.4930 2.5824 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5512 -5.4429 1.9146 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9567 -1.3892 -0.3154 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.1563 -1.4625 -1.7031 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3308 -0.2789 0.4024 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9214 -0.4038 1.6050 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0533 0.9724 0.1102 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.7835 1.0730 -1.1616 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5085 2.3633 -1.3497 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7625 2.5607 -0.8204 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4210 3.7672 -1.0521 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8380 4.7710 -1.8052 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5792 4.5403 -2.3216 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9353 3.3511 -2.0901 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3685 2.1249 0.6010 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.9872 3.0649 1.4879 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.1206 4.3094 0.8815 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0353 3.3169 2.6779 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7318 3.9212 2.1484 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0365 2.8348 1.2995 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0493 2.4903 0.2801 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8337 2.4995 -0.9063 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7737 3.2039 0.8436 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1966 4.3089 0.9348 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1328 4.5442 0.4107 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6758 5.7734 0.5466 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0384 6.0862 0.0323 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9183 3.5955 -0.2169 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2512 2.4169 0.0953 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1313 1.5968 -0.7790 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4327 0.3804 -1.3545 C 0 0 2 0 0 0 0 0 0 0 0 0 1.1346 -0.5794 -0.3929 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1626 -1.0408 -0.2531 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0273 -0.5573 -1.0269 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3972 -0.2172 -2.3796 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3477 1.2159 -0.1443 N 0 0 0 0 0 0 0 0 0 0 0 0 4.5409 1.4419 -0.4782 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6118 0.9026 0.4060 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4578 1.9818 1.0441 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4934 1.2807 1.9041 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1538 2.8784 0.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4717 -0.0318 -0.2454 N 0 0 0 0 0 0 0 0 0 0 0 0 6.3247 -1.2781 -0.3914 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3625 -2.0524 -1.1113 C 0 0 1 0 0 0 0 0 0 0 0 0 8.5284 -1.1475 -1.5106 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2542 -0.7555 -0.3918 O 0 0 0 0 0 0 0 0 0 0 0 0 10.5541 0.1750 -0.9188 S 0 0 0 0 0 0 0 0 0 0 0 0 10.8110 -0.1326 -2.3473 O 0 0 0 0 0 0 0 0 0 0 0 0 11.7669 -0.1983 -0.1049 O 0 0 0 0 0 0 0 0 0 0 0 0 10.2696 1.8110 -0.6598 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7944 -3.1809 -0.4651 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5749 -4.3513 -1.1765 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2084 -1.9285 0.1119 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8057 2.1627 -1.6211 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8043 1.8404 1.2750 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8077 5.3946 1.5570 O 0 0 0 0 0 1 0 0 0 0 0 0 -0.2045 -4.0923 2.0060 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 Na 0 0 0 0 0 15 0 0 0 0 0 0 2.8973 -4.7411 -0.2331 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6610 -4.9654 1.5952 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3954 -5.4049 0.4266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9274 -2.8209 1.6685 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0246 -2.6789 -0.1857 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1263 -4.0206 -0.1380 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3202 -1.5923 1.7673 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6567 -3.1438 -1.7104 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2436 -2.4070 1.4449 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9319 -3.9598 0.2496 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7989 -4.1069 -1.0870 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7363 -5.3583 -0.8722 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6520 -7.2267 0.2866 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4272 -7.9602 2.4976 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2744 -6.8401 3.5522 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3820 -4.9509 2.4057 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2123 -1.4428 -2.0268 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6075 -0.6989 -2.3016 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7610 -2.4286 -2.1348 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9418 0.8818 0.8989 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2068 0.8845 -2.0950 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6052 0.2967 -1.1649 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2819 1.8267 -0.2221 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4103 3.9475 -0.6438 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3193 5.7113 -2.0026 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1017 5.3038 -2.9129 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9538 3.2019 -2.5088 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9164 2.6955 1.9171 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2963 5.0347 1.5329 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5106 4.0510 3.3238 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7827 2.3966 3.1939 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1344 4.2044 2.9924 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9343 4.7631 1.4896 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9500 1.9583 2.0577 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1233 6.5436 1.0339 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4836 5.2641 -0.5572 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7328 6.4166 0.8519 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9809 6.9471 -0.6839 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3977 2.2188 -1.6620 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5727 0.7399 -1.9519 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0058 -1.2570 -2.5468 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3163 0.3730 -3.3047 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4164 -0.2323 -1.9605 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1208 0.3605 1.2422 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8417 2.6036 1.7452 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4343 1.2193 1.3239 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7179 1.9191 2.7975 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1369 0.2819 2.2357 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0871 3.2568 0.5918 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4995 2.4000 -0.8391 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5419 3.8118 -0.0998 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9137 -2.3884 -2.0832 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1031 -0.2095 -1.9380 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1490 -1.6043 -2.3044 H 0 0 0 0 0 0 0 0 0 0 0 0 10.5932 2.3633 -1.4355 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4956 -4.4839 -1.3594 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0632 -4.1993 -2.1774 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9749 -5.2403 -0.6657 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3575 -1.4593 0.3657 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2784 1.9700 -2.4678 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5707 2.3912 2.0973 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2431 -4.4334 2.0446 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0244 -3.3912 2.8624 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4519 -4.9715 2.1566 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 3 6 7 1 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 8 16 1 0 16 17 1 0 16 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 20 28 1 0 28 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 2 0 33 36 1 0 36 37 2 0 37 38 1 0 38 39 2 0 39 40 1 0 38 41 1 0 41 42 2 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 2 0 44 48 1 0 43 49 1 0 49 50 2 3 50 51 1 0 51 52 1 0 52 53 1 0 52 54 1 0 51 55 1 0 55 56 2 3 56 57 1 0 57 58 1 0 58 59 1 0 59 60 1 0 60 61 2 0 60 62 2 0 60 63 1 0 57 64 1 0 64 65 1 0 56 66 1 0 50 67 1 0 42 68 1 0 37 69 1 0 3 70 1 0 46 4 1 0 15 10 1 0 27 22 1 0 34 28 1 0 1 72 1 0 1 73 1 0 1 74 1 0 2 75 1 0 2 76 1 0 3 77 1 6 4 78 1 1 7 79 1 0 8 80 1 1 9 81 1 0 9 82 1 0 11 83 1 0 12 84 1 0 13 85 1 0 14 86 1 0 15 87 1 0 17 88 1 0 17 89 1 0 17 90 1 0 20 91 1 1 21 92 1 0 21 93 1 0 23 94 1 0 24 95 1 0 25 96 1 0 26 97 1 0 27 98 1 0 29 99 1 1 30100 1 0 31101 1 0 31102 1 0 32103 1 0 32104 1 0 33105 1 1 39106 1 0 40107 1 0 40108 1 0 40109 1 0 43110 1 6 44111 1 6 48112 1 0 48113 1 0 48114 1 0 51115 1 1 52116 1 0 53117 1 0 53118 1 0 53119 1 0 54120 1 0 54121 1 0 54122 1 0 57123 1 6 58124 1 0 58125 1 0 63126 1 0 65127 1 0 65128 1 0 65129 1 0 66130 1 0 67131 1 0 68132 1 0 70133 1 0 70134 1 0 70135 1 0 M CHG 2 69 -1 71 1 M END

Standard InCHIKey	KPKJQINJXGFAPS-NBGICTFWSA-M
Standard InCHI	InChI=1S/C47H65N7O15S.Na/c1-9-27(5)38-47(63)69-28(6)39(52-43(59)37(26(3)4)50-42(58)35(67-8)25-68-70(64,65)66)44(60)48-31(10-2)40(56)49-32-21-22-36(55)54(45(32)61)34(24-30-19-15-12-16-20-30)46(62)53(7)33(41(57)51-38)23-29-17-13-11-14-18-29;/h10-20,26-28,32-39,55H,9,21-25H2,1-8H3,(H,48,60)(H,49,56)(H,50,58)(H,51,57)(H,52,59)(H,64,65,66);/q;+1/p-1/b31-10-;/t27-,28-,32+,33+,34+,35-,36-,37+,38+,39+;/m1./s1
SMILES	CC[C@H]([C@@H]1N=C(O)[C@H](Cc2ccccc2)N(C)C(=O)[C@H](Cc2ccccc2)N2[C@H](O)CC[C@@H](C2=O)N=C(/C(=C/C)/N=C([C@H]([C@H](OC1=O)C)N=C([C@H](C(C)C)N=C([C@@H](COS(=O)(=O)O)OC)O)O)O)[O-])C.[Na+]

Calculated Properties

Physi-Chem Properties

Molecular Weight:	998.42	Volume:	973.717 ? Van der Waals volume.
Dense:	1.025	LogP:	-0.452 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.408 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.438 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	43.0
TPSA:	325.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	22.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	23.0

MedChem Properties

QED Drug-Likeness Score:	0.065	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.607	Fsp³:	0.532
MCE-18:	126.75 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.618	Fluc inhibitor:	0.048 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.034 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.846 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.013	Promiscuous compounds:	0.021

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.57	MDCK Permeability:	-5.04
Pgp-inhibitor:	0.98	Pgp-substrate:	0.998
PAMPA:	0.289 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.878
20% Bioavailability (F20%):	1.0	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.523
Plasma Protein Binding (PPB):	71.249%	Volume Distribution (VD):	-0.631
Fu:	30.012% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.001
BSEP inhibitor:	0.99

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.031 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.315

Half-life (T1/2):

2.237

ADMET: Toxicity

hERG Blockers:	0.001	hERG Blockers (10um):	0.0
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.043	Rat Oral Acute Toxicity:	0.415
Maximum Recommended Daily Dose:	0.992	Skin Sensitization:	1.0
Carcinogencity:	0.125	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.893
Drug-induced Neurotoxicity:	0.021	Ototoxicity:	0.999
Hematotoxicity:	0.212	Drug-induced Nephrotoxicity:	0.999
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.0
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.006
BCF:	0.448 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	3.241 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.942 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.167 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO33098	cyanobacteria	Phylum	n.a.	Bacteria	n.a.	n.a.	n.a.	PMID[19715320]
NPO33098	cyanobacteria	Phylum	n.a.	Bacteria	n.a.	n.a.	n.a.	PMID[23350733]
NPO33098	cyanobacteria	Phylum	n.a.	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Activity Type	# Activity
IC50	34
Activity	72
Inhibition	9

Activity Type	# Activity
Individual protein	96
Protein family	2
Others	17

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1654	Individual protein	Urokinase-type plasminogen activator	Homo sapiens	IC50	<	10000.0	nM	PMID[16933872]
NPT2785	Individual protein	Tryptase beta-1	Homo sapiens	IC50	<	10000.0	nM	PMID[16933872]
NPT1720	Individual protein	Plasminogen	Homo sapiens	IC50	<	10000.0	nM	PMID[10395508]
NPT2533	Individual protein	Coagulation factor X	Homo sapiens	IC50	<	10000.0	nM	PMID[19546358]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	<	10000.0	nM	PMID[19546358]
NPT1547	Individual protein	Cathepsin D	Homo sapiens	Activity	=	100.0	%	PMID[12951092]
NPT1090	Individual protein	Matrix metalloproteinase 13	Homo sapiens	Activity	=	100.0	%	PMID[1517739]
NPT1089	Individual protein	Matrix metalloproteinase 12	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT280	Individual protein	Matrix metalloproteinase 9	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Activity	=	100.0	%	PMID[21035332]
NPT201	Individual protein	Papain	Carica papaya	Activity	=	100.0	%	PMID[19167886]
NPT214	Individual protein	Cathepsin B	Homo sapiens	Activity	=	100.0	%	PMID[21035332]
NPT2265	Individual protein	Caspase-9	Homo sapiens	Activity	=	75.0	%	PubChem BioAssay data set
NPT1226	Individual protein	Caspase-7	Homo sapiens	Activity	=	100.0	%	PMID[20624681]
NPT277	Individual protein	Caspase-1	Homo sapiens	Activity	=	50.0	%	PMID[23316950]
NPT1654	Individual protein	Urokinase-type plasminogen activator	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT2785	Individual protein	Tryptase beta-1	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT1720	Individual protein	Plasminogen	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT2533	Individual protein	Coagulation factor X	Homo sapiens	Activity	=	100.0	%	PMID[17157006]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Activity	=	0.0	%	PMID[15050621]
NPT278	Individual protein	Cathepsin G	Homo sapiens	Activity	=	50.0	%	PMID[8632405]
NPT1592	Individual protein	Dipeptidyl peptidase IV	Homo sapiens	Activity	=	100.0	%	PMID[21534539]
NPT278	Individual protein	Cathepsin G	Homo sapiens	IC50	<	10000.0	nM	PMID[17524651]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	22.0	%	PMID[19674905]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	42.0	%	Open TG-GATES in vivo data: Organ Weight
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	34.0	%	PMID[19827833]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	46.0	%	PMID[18808182]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	53.0	%	PMID[19942326]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	49.0	%	PMID[23398362]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	56.0	%	PMID[19942326]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Inhibition	=	58.0	%	PMID[19942326]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	Activity	>	75.0	%	PMID[10087141]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	=	77.5	nM	DrugMatrix in vitro pharmacology data
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	=	144.0	nM	PMID[23357036]
NPT279	Individual protein	Leukocyte elastase	Homo sapiens	IC50	=	93.0	nM	PMID[33002682]
NPT6425	Individual protein	Kallikrein 8	Homo sapiens	IC50	<	10000.0	nM	PMID[15497936]
NPT4197	Individual protein	Coagulation factor XI	Homo sapiens	IC50	<	10000.0	nM	PMID[19546358]
NPT6254	Individual protein	Coagulation factor VII	Homo sapiens	IC50	<	10000.0	nM	PMID[19721071]
NPT6326	Individual protein	Vitamin K-dependent protein C	Homo sapiens	IC50	<	10000.0	nM	PMID[18183025]
NPT6325	Individual protein	Matrix metalloproteinase 10	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT5085	Individual protein	Cathepsin H	Homo sapiens	Activity	=	100.0	%	PMID[21035332]
NPT3579	Individual protein	Calpain 1	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT6425	Individual protein	Kallikrein 8	Homo sapiens	Activity	=	50.0	%	PMID[11551769]
NPT4197	Individual protein	Coagulation factor XI	Homo sapiens	Activity	=	75.0	%	PMID[17157006]
NPT6254	Individual protein	Coagulation factor VII	Homo sapiens	Activity	=	100.0	%	PMID[21982796]
NPT6326	Individual protein	Vitamin K-dependent protein C	Homo sapiens	Activity	=	100.0	%	PMID[8632405]
NPT6386	Individual protein	Dipeptidyl peptidase I	Homo sapiens	Activity	=	50.0	%	PMID[8632405]
NPT6416	Individual protein	Dipeptidyl peptidase VIII	Homo sapiens	Activity	=	100.0	%	PMID[10560729]
NPT6294	Individual protein	Tryptase gamma	Homo sapiens	IC50	<	10000.0	nM	PMID[16933872]
NPT5075	Individual protein	Plasma kallikrein	Homo sapiens	IC50	<	10000.0	nM	PMID[15497936]
NPT6648	Individual protein	Kallikrein 14	Homo sapiens	IC50	<	10000.0	nM	PMID[9584401]
NPT6321	Individual protein	Kallikrein 12	Homo sapiens	IC50	<	10000.0	nM	PMID[10395498]
NPT6500	Individual protein	Kallikrein 1	Homo sapiens	IC50	<	10000.0	nM	PMID[20888765]
NPT740	Individual protein	Beta-secretase 1	Homo sapiens	Activity	=	100.0	%	PMID[12932124]
NPT4015	Individual protein	Matrix metalloproteinase 14	Homo sapiens	Activity	=	100.0	%	DOI[10.6019/CHEMBL1201861]
NPT4016	Individual protein	Matrix metalloproteinase 7	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT567	Individual protein	Matrix metalloproteinase 3	Homo sapiens	Activity	=	100.0	%	PMID[1517739]
NPT69	Individual protein	Matrix metalloproteinase-1	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT6430	Individual protein	Caspase-10	Homo sapiens	Activity	=	100.0	%	PMID[20624681]
NPT979	Individual protein	Caspase-3	Homo sapiens	Activity	=	100.0	%	PubChem BioAssay data set
NPT4104	Individual protein	Caspase-2	Homo sapiens	Activity	=	75.0	%	PubChem BioAssay data set
NPT6294	Individual protein	Tryptase gamma	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT5075	Individual protein	Plasma kallikrein	Homo sapiens	Activity	=	50.0	%	PMID[12617583]
NPT6648	Individual protein	Kallikrein 14	Homo sapiens	Activity	=	75.0	%	PMID[12217376]
NPT6321	Individual protein	Kallikrein 12	Homo sapiens	Activity	=	0.0	%	PMID[12217376]
NPT6500	Individual protein	Kallikrein 1	Homo sapiens	Activity	=	100.0	%	PMID[12217376]
NPT6487	Individual protein	Dipeptidyl peptidase IX	Homo sapiens	Activity	=	100.0	%	PMID[8632405]
NPT6616	Individual protein	Tissue-type plasminogen activator	Homo sapiens	IC50	<	10000.0	nM	PMID[15497936]
NPT6352	Individual protein	Kallikrein 13	Homo sapiens	IC50	<	10000.0	nM	PMID[16252909]
NPT6580	Individual protein	Granzyme B	Homo sapiens	IC50	<	10000.0	nM	PMID[19546358]
NPT6299	Individual protein	ADAM10	Homo sapiens	Activity	=	100.0	%	DOI[10.6019/CHEMBL1201861]
NPT6515	Individual protein	ADAM9	Homo sapiens	Activity	=	100.0	%	PMID[18280170]
NPT4211	Individual protein	Caspase-8	Homo sapiens	Activity	=	100.0	%	PMID[20624681]
NPT6608	Individual protein	Caspase-5	Homo sapiens	Activity	=	100.0	%	PMID[24900739]
NPT6616	Individual protein	Tissue-type plasminogen activator	Homo sapiens	Activity	=	100.0	%	PMID[12617583]
NPT6352	Individual protein	Kallikrein 13	Homo sapiens	Activity	=	100.0	%	PMID[12217376]
NPT6580	Individual protein	Granzyme B	Homo sapiens	Activity	=	100.0	%	PMID[12217376]
NPT1644	Protein family	Trypsin	Homo sapiens	IC50	<	10000.0	nM	PMID[16933872]
NPT4971	Individual protein	Kallikrein 5	Homo sapiens	IC50	<	10000.0	nM	PMID[20888765]
NPT6373	Individual protein	Complement C1s	Homo sapiens	IC50	<	10000.0	nM	PMID[19721071]
NPT6510	Individual protein	Cathepsin E	Homo sapiens	Activity	=	100.0	%	DOI[10.6019/CHEMBL1201861]
NPT3910	Individual protein	ADAM17	Homo sapiens	Activity	=	100.0	%	DOI[10.6019/CHEMBL1201861]
NPT6520	Individual protein	Matrix metalloproteinase 11	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT569	Individual protein	Matrix metalloproteinase 8	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT568	Individual protein	Matrix metalloproteinase-2	Homo sapiens	Activity	=	100.0	%	PMID[25856683]
NPT6391	Individual protein	Cathepsin Z	Homo sapiens	Activity	=	100.0	%	PMID[21035332]
NPT601	Individual protein	Cathepsin L2	Homo sapiens	Activity	=	100.0	%	PMID[9651160]
NPT5930	Individual protein	Cathepsin S	Homo sapiens	Activity	=	100.0	%	PMID[11421737]
NPT3595	Individual protein	Cathepsin K	Homo sapiens	Activity	=	100.0	%	PMID[11421737]
NPT6470	Individual protein	Caspase-14	Homo sapiens	Activity	=	100.0	%	PMID[20420415]
NPT867	Individual protein	Caspase-6	Homo sapiens	Activity	=	100.0	%	PMID[23215246]
NPT6575	Individual protein	Caspase-4	Homo sapiens	Activity	=	100.0	%	PMID[20624681]
NPT1644	Protein family	Trypsin	Homo sapiens	Activity	=	75.0	%	PMID[17428663]
NPT4971	Individual protein	Kallikrein 5	Homo sapiens	Activity	=	75.0	%	DOI[10.6019/CHEMBL1201861]
NPT5013	Individual protein	Chymase	Homo sapiens	Activity	=	100.0	%	PMID[21982796]
NPT6373	Individual protein	Complement C1s	Homo sapiens	Activity	=	75.0	%	PMID[12061886]
NPT5013	Individual protein	Chymase	Homo sapiens	IC50	<	10000.0	nM	PMID[17524651]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	<	10000.0	nM	PMID[19161316]
NPT2	Others	Unspecified	n.a.	IC50	=	63.1	nM	PMID[19721071]
NPT2	Others	Unspecified	n.a.	IC50	=	794.33	nM	PMID[19721071]
NPT2	Others	Unspecified	n.a.	Activity	=	0.0	%	PMID[15050621]
NPT2	Others	Unspecified	n.a.	Activity	=	75.0	%	PMID[14584959]
NPT2	Others	Unspecified	n.a.	Activity	=	100.0	%	PMID[12217376]
NPT2	Others	Unspecified	n.a.	Activity	=	53.4	%	PMID[10691710]
NPT2	Others	Unspecified	n.a.	IC50	>	10000.0	nM	PMID[19161316]
NPT2	Others	Unspecified	n.a.	IC50	=	322.0	nM	PMID[19660948]
NPT2	Others	Unspecified	n.a.	IC50	=	68.0	nM	PMID[18364258]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC471053 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	11248
0.1-0.2	36838
0.2-0.3	1620
0.3-0.4	91
0.4-0.5	25
0.5-0.6	29
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.96	High Similarity	NPC471051
0.9495	High Similarity	NPC471052
0.7857	Intermediate Similarity	NPC471048
0.7748	Intermediate Similarity	NPC471050
0.6417	Remote Similarity	NPC471526
0.6016	Remote Similarity	NPC63040
0.5891	Remote Similarity	NPC163961
0.584	Remote Similarity	NPC473407
0.5833	Remote Similarity	NPC489838
0.5802	Remote Similarity	NPC489835
0.5802	Remote Similarity	NPC489836
0.5625	Remote Similarity	NPC302715
0.5615	Remote Similarity	NPC61332
0.56	Remote Similarity	NPC22883
0.5564	Remote Similarity	NPC489837
0.5556	Remote Similarity	NPC194671
0.552	Remote Similarity	NPC279871
0.552	Remote Similarity	NPC5719
0.5469	Remote Similarity	NPC269750
0.5469	Remote Similarity	NPC294951
0.5448	Remote Similarity	NPC240130
0.541	Remote Similarity	NPC306804
0.5385	Remote Similarity	NPC60516
0.5379	Remote Similarity	NPC488263
0.5349	Remote Similarity	NPC15068
0.5267	Remote Similarity	NPC159767
0.5227	Remote Similarity	NPC155506
0.521	Remote Similarity	NPC239762
0.5161	Remote Similarity	NPC62104
0.5156	Remote Similarity	NPC137627
0.5147	Remote Similarity	NPC25539
0.5077	Remote Similarity	NPC217804
0.5076	Remote Similarity	NPC230611
0.5038	Remote Similarity	NPC476227
0.5036	Remote Similarity	NPC489834

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC471053 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2311
0.1-0.2	6456
0.2-0.3	381
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data