NPASS Compound

Natural Product: NPC572650

Natural Product ID	NPC572650
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Epimedoside E
IUPAC Name	3-[(2~{S},4~{S},5~{R})-4,5-dihydroxy-6-methyl-3-[(2~{S},5~{R})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-tetrahydropyran-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-enyl)-7-[(2~{S},4~{S},5~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 102107 0 0 0 0 0 0 0 0999 V2000 4.3520 0.7834 3.7484 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6493 0.5320 2.4058 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7172 1.5850 2.0088 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9676 -0.5693 1.8029 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5080 -1.1274 0.5313 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5493 -0.3815 -0.2699 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9265 0.7096 -1.0444 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2301 1.1297 -1.0485 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8349 2.1636 -1.7504 C 0 0 2 0 0 0 0 0 0 0 0 0 5.8371 1.5829 -2.5336 O 0 0 0 0 0 0 0 0 0 0 0 0 7.0891 2.0988 -2.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0499 1.1236 -3.0590 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8582 -0.1046 -2.4049 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5578 2.1622 -0.9259 C 0 0 1 0 0 0 0 0 0 0 0 0 8.7686 2.8908 -0.9395 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5539 2.7816 -0.0102 C 0 0 2 0 0 0 0 0 0 0 0 0 6.2204 1.9859 1.0665 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3830 3.2281 -0.8194 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7912 4.3410 -1.5909 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9958 1.3747 -1.8137 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6529 0.9688 -1.8336 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2625 1.6561 -2.6167 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2977 -0.1114 -1.0623 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2192 -0.7779 -0.2942 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8028 -1.7903 0.4076 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4507 -2.2508 0.4581 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6568 -3.4293 1.3345 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2115 -3.6757 2.3751 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0599 -4.8279 3.1047 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9278 -5.7599 2.8457 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0367 -6.9091 3.6157 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7776 -5.4885 1.8031 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6395 -4.3329 1.0564 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4006 -1.6210 -0.2758 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7491 -2.0418 -0.2450 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6504 -1.5214 0.6922 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0797 -2.4797 1.5972 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9158 -3.4031 1.0722 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2053 -4.4571 2.1341 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2168 -2.7635 0.6109 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.0128 -3.7436 0.0393 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.7907 -1.8157 -0.5138 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.1121 -2.4990 -1.4838 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8107 -0.7962 0.1082 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5160 0.1253 -0.8163 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0883 1.3776 -0.5986 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0501 1.5867 -1.5473 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5060 2.8726 -1.6690 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3638 3.8340 -1.9044 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8634 5.1283 -2.0763 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5679 3.8316 -0.6175 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4276 4.1980 0.4162 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0688 2.4111 -0.4216 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4795 2.3797 0.8433 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0334 -0.5303 -1.0607 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8383 0.1056 -1.7809 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4437 1.8513 3.9430 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3598 0.3303 3.6925 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7948 0.2217 4.5189 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4389 2.2017 2.9303 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1909 2.3172 1.2894 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7799 1.2457 1.5358 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7290 -1.1984 2.3610 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1096 -2.1769 0.7687 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4214 -1.4126 -0.1129 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0858 2.6799 -2.3763 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2282 3.0598 -2.8965 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7009 1.0240 -4.0853 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0943 1.4319 -2.9410 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5868 -0.3388 -1.8027 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8266 1.1622 -0.5458 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8160 3.5339 -0.1936 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0180 3.7067 0.4185 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6759 1.1089 0.9918 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5766 3.5842 -0.1804 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2693 5.1411 -1.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2191 2.2247 -2.4342 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0626 2.2335 -3.3921 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9773 -2.9396 2.5648 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7347 -5.0363 3.9262 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8985 -7.4472 3.6076 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5622 -6.2074 1.5808 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3278 -4.2247 0.2333 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0393 -0.7639 1.3212 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5392 -3.9681 0.1950 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3651 -5.4539 1.6876 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3118 -4.5028 2.7875 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0601 -4.1555 2.7732 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7263 -2.2405 1.4162 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7521 -3.3460 -0.5073 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6939 -1.2915 -0.8691 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5980 -3.2463 -1.8777 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4622 -0.3721 0.9494 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6662 1.2591 0.3696 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0810 3.2342 -0.7952 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1592 2.9244 -2.5654 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7281 3.5237 -2.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8240 5.0507 -2.2810 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7456 4.5420 -0.7111 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5265 3.4177 1.0464 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2209 2.3276 -1.1466 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4377 3.2455 1.2801 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 2 3 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 11 14 1 0 14 15 1 0 14 16 1 0 16 17 1 0 16 18 1 0 18 19 1 0 7 20 1 0 20 21 2 0 21 22 1 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 30 32 1 0 32 33 2 0 26 34 2 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 38 40 1 0 40 41 1 0 40 42 1 0 42 43 1 0 42 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 47 48 1 0 48 49 1 0 49 50 1 0 49 51 1 0 51 52 1 0 51 53 1 0 53 54 1 0 34 55 1 0 55 56 2 0 24 6 1 0 33 27 1 0 44 36 1 0 53 46 1 0 18 9 1 0 55 23 1 0 1 57 1 0 1 58 1 0 1 59 1 0 3 60 1 0 3 61 1 0 3 62 1 0 4 63 1 0 5 64 1 0 5 65 1 0 9 66 1 6 11 67 1 0 12 68 1 0 12 69 1 0 13 70 1 0 14 71 1 1 15 72 1 0 16 73 1 1 17 74 1 0 18 75 1 0 19 76 1 0 20 77 1 0 22 78 1 0 28 79 1 0 29 80 1 0 31 81 1 0 32 82 1 0 33 83 1 0 36 84 1 1 38 85 1 0 39 86 1 0 39 87 1 0 39 88 1 0 40 89 1 1 41 90 1 0 42 91 1 6 43 92 1 0 44 93 1 0 46 94 1 1 48 95 1 0 48 96 1 0 49 97 1 6 50 98 1 0 51 99 1 0 52100 1 0 53101 1 0 54102 1 0 M END

Standard InCHIKey	XDBZJWHRPCMWOO-CLLDRPRKSA-N
Standard InCHI	InChI=1S/C37H46O19/c1-13(2)4-9-17-20(52-36-30(49)27(46)25(44)21(11-38)53-36)10-18(40)22-26(45)33(31(54-32(17)22)15-5-7-16(39)8-6-15)55-37-34(28(47)23(42)14(3)51-37)56-35-29(48)24(43)19(41)12-50-35/h4-8,10,14,19,21,23-25,27-30,34-44,46-49H,9,11-12H2,1-3H3/t14?,19-,21?,23+,24?,25-,27+,28+,29?,30?,34?,35+,36-,37+/m1/s1
SMILES	CC(C)=CCC1=C(O[C@@H]2OC(CO)[C@@H](O)[C@H](O)C2O)C=C(O)C2=C1OC(C1=CC=C(O)C=C1)=C(O[C@@H]1OC(C)[C@H](O)[C@H](O)C1O[C@@H]1OC[C@@H](O)C(O)C1O)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	794.26	Volume:	740.455 ? Van der Waals volume.
Dense:	1.073	LogP:	1.077 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.671 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.293 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	37.0
TPSA:	308.12 ? Topological Polar Surface Area.	H-Bond Acceptor:	19.0
H-Bond Donor:	11.0	Rings:	6.0
Heavy Atoms:	19.0

MedChem Properties

QED Drug-Likeness Score:	0.101	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.526	Fsp³:	0.541
MCE-18:	151.632 ? 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:	0.672	Fluc inhibitor:	0.203 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.736 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.899 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.041	Promiscuous compounds:	0.073

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.486	MDCK Permeability:	-5.105
Pgp-inhibitor:	0.0	Pgp-substrate:	1.0
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):	0.956
20% Bioavailability (F20%):	0.981	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.696
Plasma Protein Binding (PPB):	75.407%	Volume Distribution (VD):	-0.151
Fu:	25.225% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.941
OATP1B3 inhibitor:	0.985	BCRP inhibitor:	0.373
BSEP inhibitor:	0.0

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:	0.849
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.952 ? 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):

1.07

Half-life (T1/2):

4.553

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.163
Human Hepatotoxicity (H-HT):	0.6	Drug-induced Liver Injury (DILI):	0.941
AMES Toxicity:	0.845	Rat Oral Acute Toxicity:	0.084
Maximum Recommended Daily Dose:	0.09	Skin Sensitization:	0.995
Carcinogencity:	0.021	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.003
Drug-induced Neurotoxicity:	0.013	Ototoxicity:	0.999
Hematotoxicity:	0.063	Drug-induced Nephrotoxicity:	0.698
Genotoxicity:	0.769	RPMI-8226 Immunitoxicity:	0.132
A549 Cytotoxicity:	0.439	Hek293 Cytotoxicity:	0.855
BCF:	0.644 ? 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:	3.406 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.418 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.258 ? 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
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[1442064]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36300020]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
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]
NPO28569	Epimedium acuminatum	Species	Berberidaceae	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.	216.981	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	351.314	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	41.229	n.a.	n.a.	Î¼g/g	PMID[36300020]
NPO28569	Epimedium acuminatum	n.a.	n.a.	51.791	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

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

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 NPC572650 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	16575
0.1-0.2	28388
0.2-0.3	4067
0.3-0.4	557
0.4-0.5	222
0.5-0.6	39
0.6-0.7	3
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
0.6923	Remote Similarity	NPC5319
0.614	Remote Similarity	NPC25523
0.6055	Remote Similarity	NPC35119
0.5981	Remote Similarity	NPC304741
0.5946	Remote Similarity	NPC76831
0.5909	Remote Similarity	NPC32641
0.5909	Remote Similarity	NPC256188
0.5893	Remote Similarity	NPC292929
0.5776	Remote Similarity	NPC219043
0.5691	Remote Similarity	NPC192539
0.566	Remote Similarity	NPC66087
0.5652	Remote Similarity	NPC14187
0.5641	Remote Similarity	NPC48984
0.5636	Remote Similarity	NPC131745
0.5614	Remote Similarity	NPC221342
0.5614	Remote Similarity	NPC476470
0.5593	Remote Similarity	NPC480441
0.5586	Remote Similarity	NPC240306
0.5586	Remote Similarity	NPC64425
0.5565	Remote Similarity	NPC602448
0.5495	Remote Similarity	NPC255157
0.5495	Remote Similarity	NPC259896
0.5455	Remote Similarity	NPC470405
0.5455	Remote Similarity	NPC163242
0.5455	Remote Similarity	NPC272068
0.5421	Remote Similarity	NPC116458
0.5421	Remote Similarity	NPC246943
0.537	Remote Similarity	NPC170052
0.537	Remote Similarity	NPC476215
0.537	Remote Similarity	NPC276377
0.537	Remote Similarity	NPC135846
0.5333	Remote Similarity	NPC164704
0.5304	Remote Similarity	NPC142142
0.5268	Remote Similarity	NPC183672
0.5238	Remote Similarity	NPC297987
0.5221	Remote Similarity	NPC470444
0.5135	Remote Similarity	NPC473682
0.513	Remote Similarity	NPC12013
0.513	Remote Similarity	NPC11432
0.513	Remote Similarity	NPC477613
0.5082	Remote Similarity	NPC470715
0.5078	Remote Similarity	NPC480443

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC572650 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4690
0.1-0.2	4409
0.2-0.3	43
0.3-0.4	4
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6923	Remote 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