NPASS Compound

Natural Product: NPC287401

Natural Product ID	NPC287401
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cycloleonuripeptide E
IUPAC Name	n.a.
Synonyms	Cycloleonuripeptide E
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL446384
PubChem CID	11542464
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000348] Peptides [CHEMONTID:0004831] Oligopeptides

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 127130 0 0 0 0 0 0 0 0999 V2000 7.7820 0.8833 2.8225 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7100 -0.1214 2.4613 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6154 0.6384 1.7333 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0977 1.6892 2.6852 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4655 -0.2791 1.3754 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4541 0.5837 0.6478 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5173 1.7378 0.4108 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4637 3.0448 0.0773 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3803 3.4331 -1.3911 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5429 2.9527 -2.2001 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3546 4.9467 -1.5105 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1769 3.6301 0.6781 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4926 2.8321 1.3600 N 0 0 0 0 0 0 0 0 0 0 0 0 0.2725 3.0058 2.0537 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2949 4.3103 2.8227 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8658 3.0028 1.0951 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6243 4.0174 1.0175 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.7550 4.1966 0.1690 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3153 4.3469 -1.2541 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7108 3.0750 0.3893 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0741 2.2896 -0.5419 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.9885 1.1893 -0.4005 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2338 1.5566 -1.1910 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8943 2.7777 -0.7023 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9044 2.7171 0.2339 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5512 3.8290 0.7171 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1899 5.0948 0.2566 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1899 5.1709 -0.6713 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5570 4.0470 -1.1404 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4649 -0.0877 -0.9573 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1085 -1.1020 -0.3050 N 0 0 0 0 0 0 0 0 0 0 0 0 -4.0874 -1.3459 1.0932 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.4449 -1.7551 1.6386 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9732 -2.9833 0.9298 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3540 -1.9776 3.0079 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0786 -2.3996 1.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6388 -2.5141 2.5185 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5421 -3.3192 0.4576 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8153 -3.5607 -0.9028 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8079 -5.0886 -1.0290 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2038 -5.5452 0.2673 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5357 -4.2834 0.8404 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2328 -4.0742 0.1178 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5654 -5.0379 -0.0497 N 0 0 0 0 0 0 0 0 0 0 0 0 1.8070 -5.2204 -0.6445 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6817 -5.4184 -2.1817 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8671 -4.2293 -0.3748 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6317 -3.2024 0.2445 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2061 -4.3785 -0.7923 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7964 -5.4814 -1.4490 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8289 -4.8524 -2.3308 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0689 -3.4599 -1.8037 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2157 -3.3927 -0.5717 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6712 -2.0119 -0.3585 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7928 -1.4729 0.7506 N 0 0 0 0 0 0 0 0 0 0 0 0 4.0363 -1.3574 -1.4138 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1203 -2.8161 -0.3817 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3506 -0.1770 -2.3597 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2263 2.8820 1.6675 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0858 1.9017 0.3013 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8130 4.9311 0.4765 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2777 -0.1252 0.2053 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6465 1.8531 2.2751 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7208 1.1451 3.9143 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7970 0.5117 2.5815 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0801 -0.9847 1.8991 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2344 -0.5296 3.3873 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9865 1.1660 0.8414 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4457 1.4357 3.7120 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4096 2.7125 2.3947 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9956 1.6173 2.7171 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9653 -0.5148 2.3720 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2665 3.6868 0.5346 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4563 3.0537 -1.8600 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5164 3.3420 -1.8562 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4336 3.3170 -3.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5845 1.8532 -2.2786 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7952 5.4328 -0.6397 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3128 5.2952 -1.7463 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9234 5.2265 -2.4481 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1322 2.1474 2.7914 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4671 4.9940 2.3739 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0447 4.1350 3.8981 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2861 4.7737 2.7127 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2590 5.1554 0.4503 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7133 5.2726 -1.7298 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7360 3.4856 -1.8459 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2264 4.2772 -1.3181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2793 1.0789 0.6466 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9333 0.6701 -1.1493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9928 1.6867 -2.2715 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1876 1.7240 0.5901 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3433 3.7972 1.4499 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7049 5.9838 0.6413 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8945 6.1289 -1.0413 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7643 4.1231 -1.8755 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7907 -0.4270 1.6544 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1657 -0.9410 1.4541 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2721 -2.7788 -0.1011 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1441 -3.7380 0.8890 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8310 -3.4261 1.4633 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9759 -2.7252 3.2260 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0501 -3.1196 -1.5923 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7824 -3.1659 -1.2937 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1841 -5.3871 -1.9026 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8499 -5.4277 -1.0927 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3764 -6.2550 0.0751 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9015 -5.9933 0.9783 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3586 -4.4237 1.8850 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2330 -6.2117 -0.2679 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7794 -6.4780 -2.4536 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6405 -5.1197 -2.4813 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3460 -4.7260 -2.7245 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3024 -6.1715 -0.7010 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1055 -6.1575 -1.9960 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5160 -4.8441 -3.3965 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7765 -5.4059 -2.2016 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1327 -3.2758 -1.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7741 -2.6914 -2.5498 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8069 -3.6986 0.3091 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2851 -0.3715 -1.5826 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4778 -2.7045 -1.3259 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3854 -1.1029 -2.8074 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1795 2.6559 1.8508 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3217 1.9743 -0.6745 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8321 5.2290 0.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8346 0.2130 -0.6579 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 3 5 1 0 5 6 1 0 6 7 2 3 7 8 1 0 8 9 1 0 9 10 1 0 9 11 1 0 8 12 1 0 12 13 2 3 13 14 1 0 14 15 1 0 14 16 1 0 16 17 2 3 17 18 1 0 18 19 1 0 18 20 1 0 20 21 2 3 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 22 30 1 0 30 31 2 3 31 32 1 0 32 33 1 0 33 34 1 0 33 35 1 0 32 36 1 0 36 37 2 0 36 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 2 3 44 45 1 0 45 46 1 0 45 47 1 0 47 48 2 0 47 49 1 0 49 50 1 0 50 51 1 0 51 52 1 0 52 53 1 0 53 54 1 0 54 55 2 3 54 56 1 0 43 57 1 0 30 58 1 0 20 59 1 0 16 60 1 0 12 61 1 0 6 62 1 0 55 5 1 0 29 24 1 0 42 38 1 0 53 49 1 0 1 63 1 0 1 64 1 0 1 65 1 0 2 66 1 0 2 67 1 0 3 68 1 6 4 69 1 0 4 70 1 0 4 71 1 0 5 72 1 1 8 73 1 1 9 74 1 0 10 75 1 0 10 76 1 0 10 77 1 0 11 78 1 0 11 79 1 0 11 80 1 0 14 81 1 1 15 82 1 0 15 83 1 0 15 84 1 0 18 85 1 1 19 86 1 0 19 87 1 0 19 88 1 0 22 89 1 1 23 90 1 0 23 91 1 0 25 92 1 0 26 93 1 0 27 94 1 0 28 95 1 0 29 96 1 0 32 97 1 1 33 98 1 1 34 99 1 0 34100 1 0 34101 1 0 35102 1 0 39103 1 0 39104 1 0 40105 1 0 40106 1 0 41107 1 0 41108 1 0 42109 1 1 45110 1 1 46111 1 0 46112 1 0 46113 1 0 50114 1 0 50115 1 0 51116 1 0 51117 1 0 52118 1 0 52119 1 0 53120 1 1 56121 1 0 57122 1 0 58123 1 0 59124 1 0 60125 1 0 61126 1 0 62127 1 0 M END

Standard InCHIKey	NPYYAXZHUVOXOW-HGKKAUPYSA-N
Standard InCHI	InChI=1S/C43H65N9O10/c1-9-23(4)33-41(60)48-32(22(2)3)40(59)45-24(5)35(54)44-25(6)36(55)47-29(21-28-15-11-10-12-16-28)37(56)50-34(27(8)53)43(62)52-20-14-17-30(52)38(57)46-26(7)42(61)51-19-13-18-31(51)39(58)49-33/h10-12,15-16,22-27,29-34,53H,9,13-14,17-21H2,1-8H3,(H,44,54)(H,45,59)(H,46,57)(H,47,55)(H,48,60)(H,49,58)(H,50,56)/t23-,24-,25-,26-,27+,29-,30-,31-,32-,33-,34-/m0/s1
SMILES	CC[C@H](C)[C@H]1C(=N[C@@H](C(C)C)C(=N[C@@H](C)C(=N[C@@H](C)C(=N[C@@H](Cc2ccccc2)C(=N[C@@H]([C@@H](C)O)C(=O)N2CCC[C@H]2C(=N[C@@H](C)C(=O)N2CCC[C@H]2C(=N1)O)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	867.49	Volume:	873.294 ? Van der Waals volume.
Dense:	0.993	LogP:	-0.328 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.044 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.53 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	43.0
TPSA:	288.98 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.196	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.717	Fsp³:	0.651
MCE-18:	123.211 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.335	Fluc inhibitor:	0.005 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.068 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.845 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.002	Promiscuous compounds:	0.008

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.804	MDCK Permeability:	-5.176
Pgp-inhibitor:	0.998	Pgp-substrate:	1.0
PAMPA:	0.875 ? 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):	0.885
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:	0.989
Plasma Protein Binding (PPB):	68.473%	Volume Distribution (VD):	-0.284
Fu:	25.912% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.002
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.088	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.0
HLM stability:	0.553 ? 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):

0.46

Half-life (T1/2):

2.614

ADMET: Toxicity

hERG Blockers:	0.0	hERG Blockers (10um):	0.0
Human Hepatotoxicity (H-HT):	1.0	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.001	Rat Oral Acute Toxicity:	0.269
Maximum Recommended Daily Dose:	0.0	Skin Sensitization:	1.0
Carcinogencity:	0.237	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.376
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	1.0
Hematotoxicity:	0.756	Drug-induced Nephrotoxicity:	1.0
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.0
A549 Cytotoxicity:	0.0	Hek293 Cytotoxicity:	0.0
BCF:	0.289 ? 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:	3.165 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.817 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.698 ? 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
NPO30707	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16724855]
NPO30707	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30707	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30707	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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
Activity	1

Activity Type	# Activity
Tissue	1

Molecular-level activity

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

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT177	Tissue	Aorta	Rattus norvegicus	Activity	=	32.0	%	PMID[26654828]

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 NPC287401 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	14069
0.1-0.2	33711
0.2-0.3	1579
0.3-0.4	345
0.4-0.5	109
0.5-0.6	34
0.6-0.7	10
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8082	Intermediate Similarity	NPC489824
0.6974	Remote Similarity	NPC489591
0.6711	Remote Similarity	NPC489593
0.6667	Remote Similarity	NPC252878
0.6538	Remote Similarity	NPC255447
0.622	Remote Similarity	NPC479072
0.6173	Remote Similarity	NPC202521
0.6173	Remote Similarity	NPC485094
0.6163	Remote Similarity	NPC101679
0.6049	Remote Similarity	NPC489557
0.6049	Remote Similarity	NPC479068
0.5977	Remote Similarity	NPC489825
0.5977	Remote Similarity	NPC489826
0.593	Remote Similarity	NPC479074
0.5802	Remote Similarity	NPC485876
0.5797	Remote Similarity	NPC224610
0.5797	Remote Similarity	NPC113326
0.5765	Remote Similarity	NPC489556
0.5765	Remote Similarity	NPC489822
0.5765	Remote Similarity	NPC6975
0.5714	Remote Similarity	NPC302597
0.5682	Remote Similarity	NPC479070
0.5663	Remote Similarity	NPC202198
0.5658	Remote Similarity	NPC489594
0.5658	Remote Similarity	NPC153491
0.5568	Remote Similarity	NPC130309
0.5556	Remote Similarity	NPC242482
0.5507	Remote Similarity	NPC88267
0.5506	Remote Similarity	NPC136797
0.5495	Remote Similarity	NPC479069
0.5488	Remote Similarity	NPC224315
0.5408	Remote Similarity	NPC489590
0.5393	Remote Similarity	NPC322878
0.5385	Remote Similarity	NPC25565
0.5385	Remote Similarity	NPC475439
0.5294	Remote Similarity	NPC200964
0.5287	Remote Similarity	NPC489592
0.5281	Remote Similarity	NPC5194
0.52	Remote Similarity	NPC54420
0.5176	Remote Similarity	NPC46427
0.5143	Remote Similarity	NPC285926
0.5143	Remote Similarity	NPC14672
0.5109	Remote Similarity	NPC261934
0.5072	Remote Similarity	NPC194390
0.5059	Remote Similarity	NPC223956

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC287401 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2237
0.1-0.2	6397
0.2-0.3	467
0.3-0.4	44
0.4-0.5	5
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