NPASS Compound

Natural Product: NPC476378

Natural Product ID	NPC476378
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Kankanoside H2
IUPAC Name	[(2R,3R,4S,5R,6R)-5-acetyloxy-6-[2-(3,4-dihydroxyphenyl)ethoxy]-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] (Z)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms	Kankanoside H2
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL590308
PubChem CID	46228747
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0003002] Hydroxycinnamic acid esters [CHEMONTID:0000465] Coumaric acid esters

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 108112 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 -3.5691 7.2079 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8296 8.6851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0900 10.1623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3505 11.6395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2014 12.6037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4619 14.0809 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8714 14.5939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0205 13.6298 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7600 12.1525 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1319 16.0712 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3128 15.0451 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7977 4.7665 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2072 5.2795 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.4677 6.7567 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.8772 6.2437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.0263 7.2079 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.7658 8.6851 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3563 9.1981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2072 8.2339 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.2072 10.1623 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.0582 11.1265 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.0263 10.1623 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -13.4359 7.7209 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -12.0263 5.2795 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 -6.1277 0.8479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7181 0.3349 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2768 -0.1163 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0163 -1.5935 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1653 -2.5577 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9049 -4.0349 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0539 -4.9991 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.4635 -4.4861 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.7240 -3.0088 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.5749 -2.0447 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.6125 -5.4502 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 -7.1382 2.9544 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6209 7.4416 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8191 6.5786 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8086 4.7046 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9121 6.6272 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1140 3.8081 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3275 8.6066 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3523 8.9456 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5672 9.9018 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6128 10.4228 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7919 12.0907 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4300 14.1428 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7830 11.0555 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5415 16.5842 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5733 16.5223 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1167 6.1030 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3107 3.3570 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9789 6.9396 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1272 4.9447 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.9291 6.0100 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.2547 8.8679 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.9424 10.5789 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0242 11.4203 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2431 9.0132 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7217 10.4455 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -11.1447 11.3759 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.8744 9.1554 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.4879 5.6169 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6863 0.3967 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6067 -2.1065 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4953 -4.5479 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7935 -6.4763 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -12.1335 -2.4958 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.8354 -0.5674 0.0000 H 0 0 0 0 0 0 0 0 0 0 0 0 -13.0221 -4.9372 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 14 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 26 29 1 0 25 30 1 0 12 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 34 35 1 0 35 36 1 0 36 37 1 0 37 38 1 0 37 39 1 0 39 40 1 0 36 41 1 0 35 42 1 0 34 43 1 0 11 44 1 0 44 45 1 0 45 46 2 0 45 47 1 0 47 48 2 3 48 49 1 0 49 50 2 0 50 51 1 0 51 52 2 0 52 53 1 0 53 54 2 0 52 55 1 0 5 56 1 0 4 57 1 0 3 58 1 0 7 2 1 0 15 10 1 0 28 23 1 0 38 33 1 0 54 49 1 0 1 59 1 0 1 60 1 0 1 61 1 0 2 62 1 0 3 63 1 0 4 64 1 0 5 65 1 0 6 66 1 0 8 67 1 0 8 68 1 0 10 69 1 0 11 70 1 0 12 71 1 0 14 72 1 0 15 73 1 0 19 74 1 0 19 75 1 0 19 76 1 0 21 77 1 0 21 78 1 0 22 79 1 0 22 80 1 0 24 81 1 0 27 82 1 0 28 83 1 0 29 84 1 0 30 85 1 0 31 86 1 0 31 87 1 0 33 88 1 0 34 89 1 0 35 90 1 0 36 91 1 0 37 92 1 0 39 93 1 0 39 94 1 0 40 95 1 0 41 96 1 0 42 97 1 0 43 98 1 0 47 99 1 0 48100 1 0 50101 1 0 51102 1 0 53103 1 0 54104 1 0 55105 1 0 56106 1 0 57107 1 0 58108 1 0 M END

Standard InCHIKey	YVEWOLFCBHXGFW-GBSNAEPKSA-N
Standard InCHI	InChI=1S/C38H50O20/c1-17-28(45)31(48)30(47)25(54-17)15-52-35-34(58-27(44)10-6-19-3-7-21(41)8-4-19)26(16-53-37-33(50)32(49)29(46)24(14-39)56-37)57-38(36(35)55-18(2)40)51-12-11-20-5-9-22(42)23(43)13-20/h3-10,13,17,24-26,28-39,41-43,45-50H,11-12,14-16H2,1-2H3/b10-6-/t17-,24+,25-,26+,28-,29+,30-,31+,32-,33+,34+,35-,36+,37+,38+/m0/s1
SMILES	CC1C(C(C(C(O1)COC2C(C(OC(C2OC(=O)C)OCCC3=CC(=C(C=C3)O)O)COC4C(C(C(C(O4)CO)O)O)O)OC(=O)C=CC5=CC=C(C=C5)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	826.29	Volume:	775.098 ? Van der Waals volume.
Dense:	1.066	LogP:	-0.362 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.3 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.715 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	33.0
TPSA:	310.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	20.0
H-Bond Donor:	10.0	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:	5.443	Fsp³:	0.579
MCE-18:	129.5 ? 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:	0.329	Fluc inhibitor:	0.484 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.042 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.665 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.396	Promiscuous compounds:	0.501

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.167	MDCK Permeability:	-5.162
Pgp-inhibitor:	0.0	Pgp-substrate:	0.989
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:	0.952
Plasma Protein Binding (PPB):	58.639%	Volume Distribution (VD):	-0.416
Fu:	37.056% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.811	BCRP inhibitor:	0.03
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.727
HLM stability:	0.022 ? 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):

1.854

Half-life (T1/2):

3.389

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.711
Human Hepatotoxicity (H-HT):	0.329	Drug-induced Liver Injury (DILI):	0.369
AMES Toxicity:	0.879	Rat Oral Acute Toxicity:	0.149
Maximum Recommended Daily Dose:	0.271	Skin Sensitization:	0.965
Carcinogencity:	0.013	Eye Corrosion:	0.0
Eye Irritation:	0.001	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.143	Ototoxicity:	0.997
Hematotoxicity:	0.004	Drug-induced Nephrotoxicity:	0.019
Genotoxicity:	0.23	RPMI-8226 Immunitoxicity:	0.03
A549 Cytotoxicity:	0.381	Hek293 Cytotoxicity:	0.919
BCF:	0.541 ? 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:	3.023 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.006 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.083 ? 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	=	4.4	%	PMID[22168134]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	11.6	%	PMID[25871261]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	18.2	%	PMID[9644083]
NPT993	Cell line	Hepatocyte	Mus musculus	Inhibition	=	26.3	%	PMID[18198837]

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 NPC476378 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	15504
0.1-0.2	29308
0.2-0.3	4443
0.3-0.4	466
0.4-0.5	84
0.5-0.6	34
0.6-0.7	7
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9318	High Similarity	NPC476375
0.8333	Intermediate Similarity	NPC119537
0.8298	Intermediate Similarity	NPC476380
0.7732	Intermediate Similarity	NPC476381
0.7708	Intermediate Similarity	NPC476384
0.7391	Intermediate Similarity	NPC476377
0.7048	Intermediate Similarity	NPC476386
0.6566	Remote Similarity	NPC298257
0.6566	Remote Similarity	NPC175214
0.6429	Remote Similarity	NPC476376
0.6132	Remote Similarity	NPC196063
0.6132	Remote Similarity	NPC604195
0.61	Remote Similarity	NPC47471
0.6061	Remote Similarity	NPC76406
0.5963	Remote Similarity	NPC64195
0.5806	Remote Similarity	NPC34293
0.5769	Remote Similarity	NPC205864
0.5769	Remote Similarity	NPC247032
0.5714	Remote Similarity	NPC81515
0.5686	Remote Similarity	NPC611289
0.5648	Remote Similarity	NPC476382
0.5607	Remote Similarity	NPC610636
0.5556	Remote Similarity	NPC300894
0.5556	Remote Similarity	NPC23845
0.5545	Remote Similarity	NPC472350
0.5545	Remote Similarity	NPC197316
0.5545	Remote Similarity	NPC89105
0.5534	Remote Similarity	NPC476383
0.5508	Remote Similarity	NPC257970
0.55	Remote Similarity	NPC46137
0.5446	Remote Similarity	NPC470933
0.534	Remote Similarity	NPC68092
0.53	Remote Similarity	NPC475530
0.5278	Remote Similarity	NPC112
0.5263	Remote Similarity	NPC287597
0.5248	Remote Similarity	NPC260425
0.5234	Remote Similarity	NPC269141
0.5213	Remote Similarity	NPC288416
0.5189	Remote Similarity	NPC263829
0.5185	Remote Similarity	NPC105005
0.5179	Remote Similarity	NPC106818
0.5158	Remote Similarity	NPC477294
0.5146	Remote Similarity	NPC205195
0.5128	Remote Similarity	NPC229505
0.5091	Remote Similarity	NPC100998
0.505	Remote Similarity	NPC473799
0.5045	Remote Similarity	NPC96795
0.5045	Remote Similarity	NPC264632

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5607
0.1-0.2	3486
0.2-0.3	56
0.3-0.4	0
0.4-0.5	0
0.5-0.6	1
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
0.5545	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