NPASS Compound

Natural Product: NPC5319

Natural Product ID	NPC5319
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Icariin
IUPAC Name	5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxychromen-4-one
Synonyms	Icariin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL553204
PubChem CID	5318997
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 88 92 0 0 0 0 0 0 0 0999 V2000 -4.2404 -5.9452 3.3508 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8658 -5.2566 2.2957 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2088 -4.2031 1.6927 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9709 -3.8267 2.1059 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3362 -2.7700 1.4864 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8839 -2.0441 0.4444 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1304 -2.4298 0.0334 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7797 -3.5009 0.6586 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0719 -0.9957 -0.1616 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7609 -0.9677 0.0940 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0628 -0.0817 -0.3954 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4030 -0.0917 -0.1046 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9668 -1.1202 0.7942 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1065 -2.4377 0.1532 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2874 -3.0133 0.0637 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5444 -2.4221 0.5761 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3841 -4.3493 -0.5952 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2816 0.8606 -0.6329 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5925 0.7891 -0.3018 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6826 1.5659 -0.6786 C 0 0 2 0 0 0 0 0 0 0 0 0 5.6250 0.7922 -1.2686 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9386 1.0636 -1.0910 C 0 0 2 0 0 0 0 0 0 0 0 0 7.6212 0.3158 0.0327 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5363 -1.0386 -0.2260 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1560 2.5368 -1.0508 C 0 0 2 0 0 0 0 0 0 0 0 0 6.4851 3.0824 0.1895 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1636 2.4286 0.4568 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2193 3.4080 0.7522 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3791 2.9199 1.2447 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5181 3.0918 -2.1556 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8148 1.8502 -1.4731 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4707 1.8618 -1.7656 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3852 0.9207 -1.2407 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 0.9206 -1.5223 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1382 1.8399 -2.2977 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5890 -0.0349 -0.9848 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9330 0.0833 -1.3329 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8120 0.9335 -0.6055 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.8275 0.2734 0.0326 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5005 1.1756 0.8443 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6356 1.9479 1.7822 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3527 2.0407 -0.0327 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.8077 2.2107 -1.4250 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3134 2.0446 -1.4995 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6417 3.2298 -1.2073 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1223 3.5029 -1.8411 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6353 1.4925 -0.0647 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0113 2.8465 -2.6051 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8509 -6.8644 3.5190 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2078 -6.1805 3.0466 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2406 -5.3665 4.2967 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4387 -4.3140 2.9106 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3376 -2.4898 1.8418 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6207 -1.9493 -0.7780 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7687 -3.8142 0.3397 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9076 -0.7330 1.2303 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2655 -1.1977 1.6784 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2418 -2.9292 -0.2421 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3591 -3.1749 0.6202 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8678 -1.6372 -0.1218 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4402 -1.9764 1.5950 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9931 -4.2253 -1.5193 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4016 -4.7894 -0.7941 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9238 -5.0233 0.0992 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3279 2.2825 -1.4788 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4650 0.6955 -2.0308 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3012 0.5988 1.0350 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7079 0.5985 -0.0345 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4209 -1.4455 -0.2383 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2388 2.7463 -1.0307 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3726 4.1753 0.0326 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2580 1.7913 1.3517 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0964 4.0427 -0.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0039 3.6950 1.2624 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5806 2.4173 -2.8906 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4771 2.6214 -1.9085 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1960 1.4093 0.1994 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1673 0.5309 1.4924 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3312 2.9546 1.4215 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2525 2.1752 2.7024 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7891 1.3409 2.1506 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4469 3.0351 0.4855 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3350 1.5177 -2.1125 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0535 1.7730 -2.5404 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7449 3.9032 -1.9273 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3757 3.5674 -2.7753 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8377 0.9788 0.7594 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2095 3.7602 -2.1666 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 6 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 2 3 15 16 1 0 15 17 1 0 12 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 26 29 1 0 25 30 1 0 18 31 2 0 31 32 1 0 32 33 2 0 33 34 1 0 34 35 2 0 34 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 39 40 1 0 40 41 1 0 40 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 43 46 1 0 42 47 1 0 32 48 1 0 8 3 1 0 36 9 2 0 44 38 1 0 33 11 1 0 27 20 1 0 1 49 1 0 1 50 1 0 1 51 1 0 4 52 1 0 5 53 1 0 7 54 1 0 8 55 1 0 13 56 1 0 13 57 1 0 14 58 1 0 16 59 1 0 16 60 1 0 16 61 1 0 17 62 1 0 17 63 1 0 17 64 1 0 20 65 1 6 22 66 1 6 23 67 1 0 23 68 1 0 24 69 1 0 25 70 1 1 26 71 1 6 27 72 1 1 28 73 1 0 29 74 1 0 30 75 1 0 31 76 1 0 38 77 1 1 40 78 1 1 41 79 1 0 41 80 1 0 41 81 1 0 42 82 1 1 43 83 1 6 44 84 1 6 45 85 1 0 46 86 1 0 47 87 1 0 48 88 1 0 M END

Standard InCHIKey	TZJALUIVHRYQQB-XLRXWWTNSA-N
Standard InCHI	InChI=1S/C33H40O15/c1-13(2)5-10-17-19(45-33-28(42)26(40)23(37)20(12-34)46-33)11-18(35)21-24(38)31(48-32-27(41)25(39)22(36)14(3)44-32)29(47-30(17)21)15-6-8-16(43-4)9-7-15/h5-9,11,14,20,22-23,25-28,32-37,39-42H,10,12H2,1-4H3/t14-,20+,22-,23+,25+,26-,27+,28+,32-,33+/m0/s1
SMILES	COc1ccc(cc1)c1oc2c(CC=C(C)C)c(O[C@@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O)cc(c2c(=O)c1O[C@@H]1O[C@@H](C)[C@@H]([C@H]([C@H]1O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	676.24	Volume:	644.667 ? Van der Waals volume.
Dense:	1.049	LogP:	2.472 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.72 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.561 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	31.0
TPSA:	238.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	8.0	Rings:	5.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.14	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.912	Fsp³:	0.485
MCE-18:	122.694 ? 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:	0.696	Fluc inhibitor:	0.282 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.822 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.916 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.055	Promiscuous compounds:	0.152

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.227	MDCK Permeability:	-5.261
Pgp-inhibitor:	0.001	Pgp-substrate:	0.772
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):	0.868
20% Bioavailability (F20%):	0.243	30% Bioavailability (F30%):	0.991
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.031
Plasma Protein Binding (PPB):	77.804%	Volume Distribution (VD):	-0.038
Fu:	22.243% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.348
BSEP inhibitor:	0.013

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:	0.0	CYP3A4-substrate:	0.978
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

1.837

Half-life (T1/2):

4.771

ADMET: Toxicity

hERG Blockers:	0.009	hERG Blockers (10um):	0.099
Human Hepatotoxicity (H-HT):	0.69	Drug-induced Liver Injury (DILI):	0.985
AMES Toxicity:	0.933	Rat Oral Acute Toxicity:	0.014
Maximum Recommended Daily Dose:	0.01	Skin Sensitization:	0.999
Carcinogencity:	0.054	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.01
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.989
Hematotoxicity:	0.249	Drug-induced Nephrotoxicity:	0.886
Genotoxicity:	0.768	RPMI-8226 Immunitoxicity:	0.114
A549 Cytotoxicity:	0.328	Hek293 Cytotoxicity:	0.306
BCF:	0.921 ? 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:	3.688 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.574 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.652 ? 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
NPO19975	Pycnandra acuminata	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.phytochem.2007.07.001]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12081149]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	seeds	n.a.	n.a.	PMID[12762787]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12762809]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[1442064]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	root	n.a.	n.a.	PMID[15921428]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	root	n.a.	PMID[22051934]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	leaf	n.a.	PMID[24066589]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	aerial parts	herbal garden of Chungbuk National University, Cheongju, Korea	2012-Oct	PMID[24963714]
NPO31054	Epimedium brevicornum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29338226]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36300020]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	leaf	n.a.	PMID[8699184]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	aerial part	n.a.	Database[Article]
NPO4957	Epimedium brevicornu	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8129	Inocybe geophylla	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19403	Epimedium grandiflorum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13384	Epimedium sempervirens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10010	Evernia vulpina	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11339	Litsea salicifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31054	Epimedium brevicornum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8609	Hopea utilis	Species	Dipterocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5534	Alternaria kikuchiana	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7874	Helichrysum lepidissimum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1695	Monascus pilosus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12828	Dysidea tupha	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31054	Epimedium brevicornum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19403	Epimedium grandiflorum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19403	Epimedium grandiflorum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4957	Epimedium brevicornu	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31106	Epimedium wushanese	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31054	Epimedium brevicornum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4957	Epimedium brevicornu	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13384	Epimedium sempervirens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO19403	Epimedium grandiflorum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8609	Hopea utilis	Species	Dipterocarpaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5140	Dipteryx odorata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13384	Epimedium sempervirens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO633	Mesembryanthemum expansum	Species	Aizoaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1695	Monascus pilosus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19975	Pycnandra acuminata	Species	Sapotaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5534	Alternaria kikuchiana	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1689	Epimedium pubescens	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10010	Evernia vulpina	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6412	Echinacea pallida	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20569	Psychotria serpens	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26095	Hypericum revolutum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6856.1	Artemisia ludoviciana subsp. mexicana	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11506	Stipa vaseyi	Species	Poaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO218	Acer carpinifolium	Species	Sapindaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6861	Galium dasypodum	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10970	Osmorhiza aristata	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12118	Cleistopholis staudtii	Species	Annonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11339	Litsea salicifolia	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10969	Epimedium sagittatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12602	Leuzea centauroides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO940	Vernonia anisochaetoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12828	Dysidea tupha	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4759	Helleborus multifidus	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4957	Epimedium brevicornu	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4322	Scabiosa succisa	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7874	Helichrysum lepidissimum	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19403	Epimedium grandiflorum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9141	Epimedium wushanense	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8129	Inocybe geophylla	Species	Inocybaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

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
NPO28569	Epimedium acuminatum	n.a.	n.a.	20.136	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	39.542	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	253.649	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	568.042	n.a.	n.a.	Î¼g/g	PMID[36300020]

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	3
Inhibition	14
Potency	2
Activity	3
Ratio IC50	3
CC50	1

Activity Type	# Activity
Individual protein	10
Organism	8
Single protein	2
Others	4
Cell line	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT273	Individual protein	Phosphodiesterase 5A	Homo sapiens	IC50	=	5900.0	nM	PMID[18778098]
NPT72	Individual protein	Solute carrier organic anion transporter family member 1B3	Homo sapiens	Inhibition	=	126.78	%	PMID[23571415]
NPT73	Individual protein	Solute carrier organic anion transporter family member 1B1	Homo sapiens	Inhibition	=	212.53	%	PMID[23571415]
NPT21762	Single protein	Lysine-specific histone demethylase 1	Homo sapiens	IC50	=	26440.0	nM	PMID[30552007]
NPT20556	Single protein	Replicase polyprotein 1ab	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	11.86	%	DOI[10.6019/CHEMBL4495564]
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	3.88	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT692	Individual protein	Histone deacetylase 6	Homo sapiens	Inhibition	=	10.19	%	HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators
NPT59	Individual protein	DNA polymerase beta	Homo sapiens	Potency	=	63095.7	nM	PubChem BioAssay data set
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Activity	=	103.8	%	PMID[26508549]
NPT861	Individual protein	Isocitrate dehydrogenase [NADP] cytoplasmic	Homo sapiens	Activity	=	90.4	%	PMID[26508549]
NPT860	Individual protein	Phosphodiesterase 6C	Homo sapiens	Inhibition	=	45.0	%	PMID[18778098]
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	11220.2	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	7.62	%	DOI[10.21203/rs.3.rs-23951/v1]
NPT20555	Organism	SARS-CoV-2	Severe acute respiratory syndrome coronavirus 2	Inhibition	=	0.08	%	DOI[10.6019/CHEMBL4495565]
NPT26765	Cell line	TM3	Mus musculus	Activity	=	139.6	%	PMID[31091478]
NPT20	Organism	Candida albicans	Candida albicans	Inhibition	=	4.36	%	DOI[10.6019/CHEMBL4513141]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	Inhibition	=	1.41	%	DOI[10.6019/CHEMBL4513141]
NPT26765	Cell line	TM3	Mus musculus	CC50	>	200000.0	nM	PMID[31091478]
NPT19	Organism	Escherichia coli	Escherichia coli	Inhibition	=	-5.7	%	DOI[10.6019/CHEMBL4513141]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	Inhibition	=	18.03	%	DOI[10.6019/CHEMBL4513141]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.41	n.a.	PMID[19523827]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	1.59	n.a.	PMID[19523827]
NPT2	Others	Unspecified	n.a.	Ratio IC50	=	2.03	n.a.	PMID[19523827]
NPT2	Others	Unspecified	n.a.	IC50	>	100000	nM	PMID[19523827]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	Inhibition	=	19.01	%	DOI[10.6019/CHEMBL4513141]

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 NPC5319 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	12174
0.1-0.2	32437
0.2-0.3	4056
0.3-0.4	875
0.4-0.5	254
0.5-0.6	45
0.6-0.7	6
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	Natural Product ID
0.7556	Intermediate Similarity	NPC131745
0.7303	Intermediate Similarity	NPC278419
0.7303	Intermediate Similarity	NPC179198
0.617	Remote Similarity	NPC66087
0.6111	Remote Similarity	NPC289667
0.6087	Remote Similarity	NPC472459
0.6064	Remote Similarity	NPC116458
0.6064	Remote Similarity	NPC246943
0.6042	Remote Similarity	NPC251417
0.5895	Remote Similarity	NPC605784
0.5816	Remote Similarity	NPC480466
0.5714	Remote Similarity	NPC480463
0.5699	Remote Similarity	NPC64305
0.5684	Remote Similarity	NPC611303
0.5638	Remote Similarity	NPC46420
0.5625	Remote Similarity	NPC148710
0.5532	Remote Similarity	NPC297987
0.5474	Remote Similarity	NPC271692
0.5426	Remote Similarity	NPC249281
0.5417	Remote Similarity	NPC59534
0.5368	Remote Similarity	NPC95090
0.5368	Remote Similarity	NPC27408
0.5368	Remote Similarity	NPC158674
0.5368	Remote Similarity	NPC136042
0.5333	Remote Similarity	NPC124155
0.5333	Remote Similarity	NPC35119
0.5312	Remote Similarity	NPC84362
0.5312	Remote Similarity	NPC349108
0.5306	Remote Similarity	NPC120099
0.5268	Remote Similarity	NPC277532
0.5243	Remote Similarity	NPC183672
0.5204	Remote Similarity	NPC219904
0.5189	Remote Similarity	NPC32641
0.5189	Remote Similarity	NPC256188
0.5155	Remote Similarity	NPC24043
0.5155	Remote Similarity	NPC488080
0.5155	Remote Similarity	NPC169977
0.5149	Remote Similarity	NPC265115
0.5143	Remote Similarity	NPC64425
0.5104	Remote Similarity	NPC77672
0.5104	Remote Similarity	NPC133671
0.5104	Remote Similarity	NPC135391
0.5104	Remote Similarity	NPC78263
0.5104	Remote Similarity	NPC250069
0.5088	Remote Similarity	NPC470716
0.5052	Remote Similarity	NPC8573
0.5051	Remote Similarity	NPC168584
0.5051	Remote Similarity	NPC60735
0.5051	Remote Similarity	NPC26230
0.5051	Remote Similarity	NPC488071
0.505	Remote Similarity	NPC276377
0.505	Remote Similarity	NPC355481
0.5047	Remote Similarity	NPC606657
0.5044	Remote Similarity	NPC470715

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC5319 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3434
0.1-0.2	5611
0.2-0.3	91
0.3-0.4	9
0.4-0.5	4
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	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD7804	Clinical (unspecified phase)

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