NPASS Compound

Natural Product: NPC475171

Natural Product ID	NPC475171
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cynarasaponin C
IUPAC Name	(2R,3R,4R,5S,6S)-6-[[(3S,4R,4aR,6aR,6bS,8aS,11R,12S,12aS,14aR,14bR)-4-(hydroxymethyl)-4,6a,6b,11,12,14b-hexamethyl-8a-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-2,3,4a,5,6,7,8,9,10,11,12,12a,14,14a-tetradecahydro-1H-picen-3-yl]oxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
Synonyms	Cynarasaponin C
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL500005
PubChem CID	44566329
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

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 123129 0 0 0 0 0 0 0 0999 V2000 9.2326 2.2268 4.2891 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9350 1.8262 3.9923 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7687 1.6820 2.4949 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4640 1.2812 2.2032 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4193 0.9661 0.8584 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2939 0.1857 0.5240 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3534 -1.0775 -0.0224 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4825 -1.5715 -0.2397 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0804 -1.8386 -0.3480 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5453 -3.1064 -0.9397 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4031 -3.2315 -2.4221 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1992 -1.9314 -3.1264 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9375 -1.2658 -2.5651 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1541 -0.9806 -1.1405 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9057 -0.8114 -0.3290 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5287 0.4185 -0.1054 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3243 0.8234 0.6697 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6396 -0.2894 0.3452 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1254 -1.5366 0.9616 C 0 0 1 0 0 0 0 0 0 0 0 0 1.1151 -1.9330 0.2114 C 0 0 2 0 0 0 0 0 0 0 0 0 2.1308 -2.6910 1.0532 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5211 -2.1298 1.0276 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7205 -2.9527 -0.8367 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2913 -1.3782 2.4217 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2601 -2.4930 1.0163 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3428 -2.3618 0.0080 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8419 -0.9826 -0.2484 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0752 0.0705 0.4781 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.5212 0.4609 1.8317 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3103 1.3535 -0.3506 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5237 1.3452 -1.1833 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6959 0.5446 -0.7590 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3342 -0.8447 -0.2646 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0217 -1.2015 1.0070 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8295 -1.8365 -1.3326 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2223 -1.7403 -1.3856 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5208 1.2034 0.1668 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7604 1.5400 -0.2806 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.6969 0.8253 0.5087 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.9993 1.1997 0.1793 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.9179 0.2367 0.8399 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5013 -0.7133 1.5515 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.3051 0.3311 0.7090 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3237 2.5746 0.7418 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.0048 3.2101 1.1007 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.0869 3.0106 -0.0871 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7418 3.5091 -1.2115 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4843 2.6679 2.2638 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.9504 3.3549 -0.2043 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8206 0.0348 -3.3977 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9118 -2.2889 -4.5927 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5038 2.2181 0.0103 C 0 0 1 0 0 0 0 0 0 0 0 0 7.8188 2.8897 0.3427 C 0 0 2 0 0 0 0 0 0 0 0 0 8.0826 2.9878 1.8094 C 0 0 2 0 0 0 0 0 0 0 0 0 9.4483 3.2264 1.9856 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9282 4.1396 -0.2661 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5293 1.8731 -1.3237 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8573 1.5171 4.0324 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1814 2.5400 4.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7900 0.8220 4.4384 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4947 0.9126 2.1297 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3192 0.3724 0.6117 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9416 -3.9474 -0.4817 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5954 -3.3716 -0.6712 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5402 -3.8794 -2.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2987 -3.7128 -2.8764 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0639 -1.2675 -3.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0753 -1.8253 -2.8873 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6770 0.0341 -1.1860 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0987 1.2968 -0.4906 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0526 1.8173 0.4105 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6166 0.8605 1.7252 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5220 -0.4511 -0.7733 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2256 -3.7647 0.7692 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8874 -2.7356 2.1301 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1992 -2.8795 1.4817 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6196 -1.2188 1.6528 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6448 -3.4621 -1.2662 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1492 -2.5947 -1.6683 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3310 -3.8133 -0.2606 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4815 -0.7527 2.9781 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1317 -2.3673 2.8990 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2225 -0.8797 2.6010 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8163 -2.3674 2.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0257 -3.5695 1.0914 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0763 -2.9502 -0.9059 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2250 -2.9490 0.4099 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5871 -0.8144 -1.3531 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7955 -0.2877 2.5464 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7011 1.1248 2.2487 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3730 1.2087 1.8211 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4355 1.4163 -1.0665 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2175 2.2609 0.2856 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3018 1.1044 -2.2690 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8847 2.4183 -1.2402 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3649 0.4729 -1.6722 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3721 -0.2959 1.5847 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9656 -1.7664 0.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4191 -1.8729 1.6533 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4403 -1.5368 -2.3319 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5946 -2.8715 -1.0931 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5806 -1.7028 -2.3078 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9900 1.2751 -1.3100 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1788 1.1427 -0.9213 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.8815 -0.4837 0.5253 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.9832 2.5162 1.6321 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1550 4.2873 1.2330 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1901 3.6222 0.0775 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4305 2.9906 -1.9975 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9096 3.3335 2.7532 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7940 2.9078 -0.4487 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7789 0.5571 -3.3048 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9332 0.6181 -3.0906 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7350 -0.3262 -4.4491 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1937 -1.5020 -5.2899 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5997 -3.1526 -4.8205 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8866 -2.6941 -4.7238 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6922 2.9236 0.2085 H 0 0 0 0 0 0 0 0 0 0 0 0 8.6387 2.2493 -0.0974 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5183 3.8257 2.2634 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9557 3.1835 1.1175 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0476 4.8618 0.3717 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9927 2.5632 -1.8332 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 1 0 6 7 1 0 7 8 2 0 9 7 1 1 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 20 23 1 6 19 24 1 1 19 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 1 28 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 1 33 35 1 0 35 36 1 0 32 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 41 42 2 0 41 43 1 0 40 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 45 48 1 0 44 49 1 0 13 50 1 0 12 51 1 0 5 52 1 0 52 53 1 0 53 54 1 0 54 55 1 0 53 56 1 0 52 57 1 0 54 3 1 0 22 9 1 0 33 27 1 0 46 38 1 0 14 9 1 0 20 15 1 0 28 18 1 0 1 58 1 0 2 59 1 0 2 60 1 0 3 61 1 6 5 62 1 6 10 63 1 0 10 64 1 0 11 65 1 0 11 66 1 0 12 67 1 6 13 68 1 1 14 69 1 6 16 70 1 0 17 71 1 0 17 72 1 0 18 73 1 6 21 74 1 0 21 75 1 0 22 76 1 0 22 77 1 0 23 78 1 0 23 79 1 0 23 80 1 0 24 81 1 0 24 82 1 0 24 83 1 0 25 84 1 0 25 85 1 0 26 86 1 0 26 87 1 0 27 88 1 6 29 89 1 0 29 90 1 0 29 91 1 0 30 92 1 0 30 93 1 0 31 94 1 0 31 95 1 0 32 96 1 6 34 97 1 0 34 98 1 0 34 99 1 0 35100 1 0 35101 1 0 36102 1 0 38103 1 6 40104 1 6 43105 1 0 44106 1 1 45107 1 1 46108 1 1 47109 1 0 48110 1 0 49111 1 0 50112 1 0 50113 1 0 50114 1 0 51115 1 0 51116 1 0 51117 1 0 52118 1 6 53119 1 6 54120 1 1 55121 1 0 56122 1 0 57123 1 0 M END

Standard InCHIKey	UHQNVKKALWJDQL-ZIJXJSMDSA-N
Standard InCHI	InChI=1S/C42H66O15/c1-19-9-14-42(37(53)57-35-31(49)28(46)27(45)22(17-43)54-35)16-15-40(5)21(26(42)20(19)2)7-8-24-38(3)12-11-25(39(4,18-44)23(38)10-13-41(24,40)6)55-36-32(50)29(47)30(48)33(56-36)34(51)52/h7,19-20,22-33,35-36,43-50H,8-18H2,1-6H3,(H,51,52)/t19-,20+,22-,23-,24-,25+,26+,27-,28+,29-,30-,31-,32+,33-,35+,36+,38+,39+,40-,41-,42+/m1/s1
SMILES	OC[C@H]1O[C@@H](OC(=O)[C@@]23CC[C@H]([C@@H]([C@H]3C3=CC[C@H]4[C@@]([C@@]3(CC2)C)(C)CC[C@@H]2[C@]4(C)CC[C@@H]([C@@]2(C)CO)O[C@H]2O[C@@H](C(=O)O)[C@@H]([C@H]([C@@H]2O)O)O)C)C)[C@@H]([C@H]([C@@H]1O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	810.44	Volume:	799.037 ? Van der Waals volume.
Dense:	1.014	LogP:	1.858 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.458 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.426 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	40.0
TPSA:	253.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	9.0	Rings:	7.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.1	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.954	Fsp³:	0.905
MCE-18:	151.25 ? 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:	0.83	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.057 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.163	Promiscuous compounds:	0.135

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.241	MDCK Permeability:	-5.116
Pgp-inhibitor:	0.0	Pgp-substrate:	0.027
PAMPA:	1.0 ? 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):	0.073
20% Bioavailability (F20%):	0.352	30% Bioavailability (F30%):	0.926
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.303	MRP1:	0.446
Plasma Protein Binding (PPB):	71.126%	Volume Distribution (VD):	-0.421
Fu:	21.915% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.092	BCRP inhibitor:	0.003
BSEP inhibitor:	0.006

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.063
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.872
HLM stability:	0.003 ? 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):

0.136

Half-life (T1/2):

2.821

ADMET: Toxicity

hERG Blockers:	0.001	hERG Blockers (10um):	0.003
Human Hepatotoxicity (H-HT):	0.544	Drug-induced Liver Injury (DILI):	0.885
AMES Toxicity:	0.694	Rat Oral Acute Toxicity:	0.007
Maximum Recommended Daily Dose:	0.003	Skin Sensitization:	1.0
Carcinogencity:	0.089	Eye Corrosion:	0.0
Eye Irritation:	0.003	Respiratory Toxicity:	0.008
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.993
Hematotoxicity:	0.65	Drug-induced Nephrotoxicity:	0.994
Genotoxicity:	0.49	RPMI-8226 Immunitoxicity:	0.111
A549 Cytotoxicity:	0.322	Hek293 Cytotoxicity:	0.087
BCF:	0.611 ? 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:	3.46 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.115 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.197 ? 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
NPO33035	ilex kudincha	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10425145]
NPO33035	ilex kudincha	Species	Aquifoliaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10479318]

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
Inhibition	2

Activity Type	# Activity
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1214	Individual protein	Acyl coenzyme A:cholesterol acyltransferase 1	Homo sapiens	Inhibition	=	63.9	%	PMID[12762807]
NPT1214	Individual protein	Acyl coenzyme A:cholesterol acyltransferase 1	Homo sapiens	Inhibition	=	29.0	%	PMID[15646539]

In vitro activity

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

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 NPC475171 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	19635
0.1-0.2	25202
0.2-0.3	3756
0.3-0.4	821
0.4-0.5	324
0.5-0.6	96
0.6-0.7	16
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
0.8172	Intermediate Similarity	NPC473884
0.7835	Intermediate Similarity	NPC11551
0.7449	Intermediate Similarity	NPC75417
0.7423	Intermediate Similarity	NPC157868
0.7273	Intermediate Similarity	NPC242840
0.699	Remote Similarity	NPC31193
0.6632	Remote Similarity	NPC110139
0.6632	Remote Similarity	NPC108709
0.65	Remote Similarity	NPC179434
0.6458	Remote Similarity	NPC224121
0.6321	Remote Similarity	NPC251768
0.6321	Remote Similarity	NPC159309
0.6321	Remote Similarity	NPC86222
0.6168	Remote Similarity	NPC40775
0.6162	Remote Similarity	NPC256798
0.6139	Remote Similarity	NPC189884
0.6139	Remote Similarity	NPC138334
0.6091	Remote Similarity	NPC114484
0.6082	Remote Similarity	NPC57362
0.6036	Remote Similarity	NPC301449
0.6036	Remote Similarity	NPC601290
0.5981	Remote Similarity	NPC192791
0.5963	Remote Similarity	NPC475591
0.5963	Remote Similarity	NPC236870
0.5849	Remote Similarity	NPC473373
0.5825	Remote Similarity	NPC90856
0.5825	Remote Similarity	NPC473481
0.5818	Remote Similarity	NPC118440
0.5804	Remote Similarity	NPC281148
0.5794	Remote Similarity	NPC295371
0.5714	Remote Similarity	NPC64715
0.5701	Remote Similarity	NPC482748
0.5673	Remote Similarity	NPC30397
0.5664	Remote Similarity	NPC114692
0.5657	Remote Similarity	NPC204407
0.5657	Remote Similarity	NPC237503
0.5652	Remote Similarity	NPC187290
0.5631	Remote Similarity	NPC209894
0.5612	Remote Similarity	NPC167383
0.5607	Remote Similarity	NPC108748
0.56	Remote Similarity	NPC37739
0.5575	Remote Similarity	NPC95437
0.5567	Remote Similarity	NPC191763
0.5566	Remote Similarity	NPC235841
0.5566	Remote Similarity	NPC297208
0.5565	Remote Similarity	NPC187618
0.5556	Remote Similarity	NPC46388
0.5534	Remote Similarity	NPC128925
0.5526	Remote Similarity	NPC236657
0.5524	Remote Similarity	NPC204458
0.5524	Remote Similarity	NPC214484
0.5495	Remote Similarity	NPC309714
0.549	Remote Similarity	NPC286347
0.5487	Remote Similarity	NPC131469
0.5487	Remote Similarity	NPC611191
0.5481	Remote Similarity	NPC294112
0.5481	Remote Similarity	NPC480937
0.5481	Remote Similarity	NPC607754
0.547	Remote Similarity	NPC11242
0.5463	Remote Similarity	NPC235405
0.5446	Remote Similarity	NPC479080
0.5446	Remote Similarity	NPC101744
0.5431	Remote Similarity	NPC480474
0.5429	Remote Similarity	NPC47063
0.5421	Remote Similarity	NPC48499
0.5413	Remote Similarity	NPC249848
0.5413	Remote Similarity	NPC107966
0.5392	Remote Similarity	NPC137917
0.5392	Remote Similarity	NPC68419
0.536	Remote Similarity	NPC258617
0.5327	Remote Similarity	NPC78046
0.5321	Remote Similarity	NPC475516
0.5299	Remote Similarity	NPC120116
0.5273	Remote Similarity	NPC58448
0.5263	Remote Similarity	NPC258885
0.5259	Remote Similarity	NPC247315
0.5259	Remote Similarity	NPC482728
0.525	Remote Similarity	NPC313110
0.5243	Remote Similarity	NPC177246
0.5234	Remote Similarity	NPC269095
0.5234	Remote Similarity	NPC480938
0.5229	Remote Similarity	NPC136877
0.5225	Remote Similarity	NPC39211
0.5225	Remote Similarity	NPC472949
0.5221	Remote Similarity	NPC124296
0.5221	Remote Similarity	NPC30735
0.5214	Remote Similarity	NPC218954
0.5203	Remote Similarity	NPC470218
0.5196	Remote Similarity	NPC116794
0.5192	Remote Similarity	NPC271138
0.5192	Remote Similarity	NPC102914
0.5185	Remote Similarity	NPC270667
0.5185	Remote Similarity	NPC29069
0.5182	Remote Similarity	NPC139894
0.5172	Remote Similarity	NPC134835
0.5169	Remote Similarity	NPC480473
0.5146	Remote Similarity	NPC606107
0.514	Remote Similarity	NPC480943
0.514	Remote Similarity	NPC195132
0.5135	Remote Similarity	NPC150400
0.5133	Remote Similarity	NPC223301
0.5133	Remote Similarity	NPC171544
0.513	Remote Similarity	NPC235438
0.512	Remote Similarity	NPC4749
0.512	Remote Similarity	NPC82380
0.512	Remote Similarity	NPC244296
0.5098	Remote Similarity	NPC605954
0.5096	Remote Similarity	NPC7870
0.5096	Remote Similarity	NPC310014
0.5096	Remote Similarity	NPC269315
0.5096	Remote Similarity	NPC75747
0.5091	Remote Similarity	NPC603870
0.5079	Remote Similarity	NPC21691
0.5045	Remote Similarity	NPC309780
0.5045	Remote Similarity	NPC59804
0.5044	Remote Similarity	NPC473343
0.5044	Remote Similarity	NPC469946

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC475171 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6343
0.1-0.2	2733
0.2-0.3	68
0.3-0.4	5
0.4-0.5	1
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