NPASS Compound

Natural Product: NPC476384

Natural Product ID	NPC476384
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kankanoside I
IUPAC Name	[(2R,3R,4R,5R,6R)-6-[2-(3,4-dihydroxyphenyl)ethoxy]-5-hydroxy-2-[[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]-4-[[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]methoxy]oxan-3-yl] (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms	Kankanoside I
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL590458
PubChem CID	46228748
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

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

Chemical Representations

RDKit 2D 104108 0 0 0 0 0 0 0 0999 V2000 2.6491 0.9642 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 -1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7500 1.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7500 1.2990 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 1.8121 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 2.3251 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8296 3.8023 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2391 3.2893 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3882 4.2535 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1277 5.7307 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7181 6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 5.2795 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 4.7665 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0105 5.7307 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2709 7.2079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3991 5.2176 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5481 6.1818 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9577 5.6688 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2181 4.1916 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6277 3.6786 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7768 4.6427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5163 6.1199 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1067 6.6330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1863 4.1297 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8882 2.2013 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5691 7.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 8.1721 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 9.6493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1805 9.6493 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4305 10.9483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1805 12.2474 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6805 12.2474 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4305 10.9483 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 12.7604 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4996 13.2734 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4410 13.7246 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7186 11.9125 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2291 9.1362 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7977 4.7665 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0582 6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3186 7.7209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5791 9.1981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4300 10.1623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6905 11.6395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1001 12.1525 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.2491 11.1884 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.9887 9.7112 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3605 13.6298 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.5415 12.6037 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3882 2.3251 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6491 -0.9642 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 -2.7762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1595 -1.8121 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7981 1.9284 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6132 -0.1849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6849 2.1132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6491 -0.9642 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4895 -2.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1595 -1.8121 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1686 0.4341 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4895 2.7762 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4785 3.1486 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5215 1.1018 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3407 3.9852 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4891 1.9902 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2909 3.0555 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4681 7.5427 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6663 6.4775 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6595 3.7404 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2877 7.6590 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0691 3.2274 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6653 7.0841 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8463 8.1102 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3354 5.0939 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2977 1.6883 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6661 8.2309 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4720 6.1849 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1420 9.3119 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4410 8.1721 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8275 10.1314 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2291 12.7604 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4200 13.7246 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5770 14.1699 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6031 11.3508 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7600 14.7506 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2919 14.6887 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1281 11.3995 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4871 9.9532 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6879 6.8539 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.5354 5.9832 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8414 7.9814 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7959 7.4604 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0205 9.6493 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.6587 11.7014 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1377 8.7470 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7701 14.1428 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8019 14.0809 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8497 2.6625 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0586 -0.4512 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6386 -3.7404 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4200 -3.2893 0.0000 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 6 8 1 0 8 9 1 0 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 1 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 2 3 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 23 28 1 0 14 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 35 37 1 0 37 38 1 0 34 39 1 0 33 40 1 0 32 41 1 0 12 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 2 0 46 47 1 0 47 48 2 0 48 49 1 0 49 50 2 0 48 51 1 0 47 52 1 0 11 53 1 0 5 54 1 0 4 55 1 0 3 56 1 0 7 2 1 0 15 10 1 0 26 21 1 0 36 31 1 0 50 45 1 0 1 57 1 0 1 58 1 0 1 59 1 0 2 60 1 0 3 61 1 0 4 62 1 0 5 63 1 0 6 64 1 0 8 65 1 0 8 66 1 0 10 67 1 0 11 68 1 0 12 69 1 0 14 70 1 0 15 71 1 0 19 72 1 0 20 73 1 0 22 74 1 0 25 75 1 0 26 76 1 0 27 77 1 0 28 78 1 0 29 79 1 0 29 80 1 0 31 81 1 0 32 82 1 0 33 83 1 0 34 84 1 0 35 85 1 0 37 86 1 0 37 87 1 0 38 88 1 0 39 89 1 0 40 90 1 0 41 91 1 0 43 92 1 0 43 93 1 0 44 94 1 0 44 95 1 0 46 96 1 0 49 97 1 0 50 98 1 0 51 99 1 0 52100 1 0 53101 1 0 54102 1 0 55103 1 0 56104 1 0 M END

Standard InCHIKey	CZWLUSDMEFNFRT-HQVYTBQRSA-N
Standard InCHI	InChI=1S/C36H48O20/c1-15-26(43)29(46)28(45)23(53-15)13-51-34-32(49)36(50-9-8-17-3-6-19(39)21(41)11-17)55-24(14-52-35-31(48)30(47)27(44)22(12-37)54-35)33(34)56-25(42)7-4-16-2-5-18(38)20(40)10-16/h2-7,10-11,15,22-24,26-41,43-49H,8-9,12-14H2,1H3/b7-4+/t15-,22+,23-,24+,26-,27+,28-,29+,30-,31+,32+,33+,34+,35+,36+/m0/s1
SMILES	CC1C(C(C(C(O1)COC2C(C(OC(C2OC(=O)C=CC3=CC(=C(C=C3)O)O)COC4C(C(C(C(O4)CO)O)O)O)OCCC5=CC(=C(C=C5)O)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	800.27	Volume:	743.142 ? Van der Waals volume.
Dense:	1.077	LogP:	-1.074 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.191 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.441 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	15.0	Rigid Bonds:	32.0
TPSA:	324.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	20.0
H-Bond Donor:	12.0	Rings:	5.0
Heavy Atoms:	20.0

MedChem Properties

QED Drug-Likeness Score:	0.051	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.441	Fsp³:	0.583
MCE-18:	130.474 ? 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:	1	PAINS Alert:	1
Colloidal aggregators:	0.33	Fluc inhibitor:	0.587 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.171 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.737 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.424	Promiscuous compounds:	0.624

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.421	MDCK Permeability:	-5.17
Pgp-inhibitor:	0.0	Pgp-substrate:	0.977
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):	1.0
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:	0.967
Plasma Protein Binding (PPB):	53.424%	Volume Distribution (VD):	-0.413
Fu:	41.482% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.774	BCRP inhibitor:	0.049
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.539	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.94
HLM stability:	0.069 ? 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):

2.002

Half-life (T1/2):

3.9

ADMET: Toxicity

hERG Blockers:	0.059	hERG Blockers (10um):	0.797
Human Hepatotoxicity (H-HT):	0.272	Drug-induced Liver Injury (DILI):	0.375
AMES Toxicity:	0.893	Rat Oral Acute Toxicity:	0.129
Maximum Recommended Daily Dose:	0.259	Skin Sensitization:	0.994
Carcinogencity:	0.009	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.027	Ototoxicity:	0.999
Hematotoxicity:	0.002	Drug-induced Nephrotoxicity:	0.011
Genotoxicity:	0.177	RPMI-8226 Immunitoxicity:	0.021
A549 Cytotoxicity:	0.765	Hek293 Cytotoxicity:	0.851
BCF:	0.543 ? 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:	3.008 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.06 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.034 ? 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
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	fresh stems	n.a.	n.a.	PMID[20159656]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO6964	Cistanche tubulosa	Species	Orobanchaceae	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

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	4

Activity Type	# Activity
Cell line	4

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
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	3.9	%	PMID[22168134]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	13.6	%	DOI[10.6019/CHEMBL1201861]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	25.9	%	PMID[9644083]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	27.7	%	PMID[12828469]

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 NPC476384 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	17296
0.1-0.2	28071
0.2-0.3	3907
0.3-0.4	470
0.4-0.5	50
0.5-0.6	28
0.6-0.7	23
0.7-0.8	0
0.8-0.85	3
0.85-0.9	1
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9318	High Similarity	NPC476380
0.9318	High Similarity	NPC476381
0.8632	High Similarity	NPC476386
0.8261	Intermediate Similarity	NPC476375
0.8202	Intermediate Similarity	NPC298257
0.8202	Intermediate Similarity	NPC175214
0.7708	Intermediate Similarity	NPC476378
0.764	Intermediate Similarity	NPC76406
0.7473	Intermediate Similarity	NPC476376
0.72	Intermediate Similarity	NPC64195
0.7053	Intermediate Similarity	NPC205864
0.7053	Intermediate Similarity	NPC247032
0.6989	Remote Similarity	NPC611289
0.6939	Remote Similarity	NPC300894
0.6939	Remote Similarity	NPC23845
0.6703	Remote Similarity	NPC81515
0.6667	Remote Similarity	NPC472350
0.6667	Remote Similarity	NPC197316
0.6667	Remote Similarity	NPC89105
0.6633	Remote Similarity	NPC119537
0.6632	Remote Similarity	NPC476377
0.6602	Remote Similarity	NPC470933
0.6311	Remote Similarity	NPC106818
0.6306	Remote Similarity	NPC257970
0.6263	Remote Similarity	NPC269141
0.6224	Remote Similarity	NPC47471
0.6214	Remote Similarity	NPC476382
0.6211	Remote Similarity	NPC205195
0.6204	Remote Similarity	NPC229505
0.6162	Remote Similarity	NPC476385
0.6122	Remote Similarity	NPC476383
0.6117	Remote Similarity	NPC259347
0.6075	Remote Similarity	NPC87403
0.604	Remote Similarity	NPC252292
0.6	Remote Similarity	NPC260425
0.5889	Remote Similarity	NPC287597
0.5877	Remote Similarity	NPC470927
0.5876	Remote Similarity	NPC64141
0.5865	Remote Similarity	NPC96795
0.5865	Remote Similarity	NPC264632
0.5825	Remote Similarity	NPC112
0.5816	Remote Similarity	NPC483705
0.5769	Remote Similarity	NPC100998
0.5714	Remote Similarity	NPC886
0.5714	Remote Similarity	NPC483706
0.5612	Remote Similarity	NPC46137
0.56	Remote Similarity	NPC68092
0.5505	Remote Similarity	NPC196063
0.5505	Remote Similarity	NPC604195
0.5495	Remote Similarity	NPC470934
0.5435	Remote Similarity	NPC477294
0.5426	Remote Similarity	NPC34293
0.5377	Remote Similarity	NPC296954
0.5327	Remote Similarity	NPC34927
0.5288	Remote Similarity	NPC263829
0.5278	Remote Similarity	NPC610636
0.5238	Remote Similarity	NPC266045
0.5234	Remote Similarity	NPC476397
0.5189	Remote Similarity	NPC34587
0.5175	Remote Similarity	NPC306890
0.513	Remote Similarity	NPC94871
0.5106	Remote Similarity	NPC477293
0.5045	Remote Similarity	NPC141455

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476384 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5631
0.1-0.2	3464
0.2-0.3	53
0.3-0.4	1
0.4-0.5	0
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
0.6667	Remote Similarity	NPD7266	Phase 2

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