NPASS Compound

Natural Product: NPC264336

Natural Product ID	NPC264336
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Elaeodendroside V
IUPAC Name	3-[(3S,5S,8R,9S,10R,11R,13R,14S,17R)-3-[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[(2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]oxy-5,11,14-trihydroxy-10-(hydroxymethyl)-13-methyl-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-2H-furan-5-one
Synonyms	elaeodendroside V
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL501316
PubChem CID	42636949
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001125] Steroid lactones [CHEMONTID:0001555] Cardenolides and derivatives [CHEMONTID:0001559] Cardenolide glycosides 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 3D 105111 0 0 0 0 0 0 0 0999 V2000 3.3184 2.5129 -2.7300 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4298 1.4149 -1.7061 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8192 0.8234 -1.6099 C 0 0 2 0 0 0 0 0 0 0 0 0 4.7262 -0.6609 -1.6338 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6818 -1.0783 -0.5828 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3759 -0.5101 -1.0337 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5711 0.3831 -2.0965 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4831 -1.4814 -1.4551 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2657 -1.3913 -0.7229 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8378 -1.3833 -1.7200 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7026 -2.5779 -1.5843 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3705 -2.6843 -0.2109 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9125 -4.0853 -0.1449 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8163 -4.4275 -1.1096 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3205 -1.5946 0.0612 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7805 -1.5845 1.4709 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.6574 -1.3607 2.4669 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3349 -1.4601 1.7425 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2638 -2.6368 0.8393 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0900 -2.5733 0.1632 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2796 -3.7777 1.6407 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8386 -0.5607 1.8071 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3963 0.8679 1.6309 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7433 1.6147 1.6327 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7643 0.6289 1.1557 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.9429 0.4957 2.0504 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.1715 0.8003 1.6615 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.1154 0.5760 2.7412 C 0 0 0 0 0 0 0 0 0 0 0 0 -11.3784 0.7492 2.7584 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.3931 0.1217 3.8044 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0439 0.0331 3.4458 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0092 -0.6497 0.9004 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.8045 -1.8941 1.1725 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5413 -0.5750 -0.5346 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4667 -1.5088 -0.9140 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9652 -0.9967 -2.1372 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1662 -0.7959 3.1454 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0120 -0.6790 0.6853 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9101 -1.3275 -1.4153 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5621 1.3344 -0.5831 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6295 2.1300 -0.9314 C 0 0 1 0 0 0 0 0 0 0 0 0 6.4144 3.5142 -0.3623 C 0 0 1 0 0 0 0 0 0 0 0 0 7.7129 4.0721 0.1149 C 0 0 1 0 0 0 0 0 0 0 0 0 8.9053 3.6624 -0.7381 C 0 0 1 0 0 0 0 0 0 0 0 0 8.9339 2.1540 -0.8939 C 0 0 1 0 0 0 0 0 0 0 0 0 10.1063 1.5425 -0.1730 C 0 0 0 0 0 0 0 0 0 0 0 0 10.1621 0.1611 -0.2992 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7681 1.5988 -0.3539 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9184 4.2866 -1.9682 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6924 5.4719 0.1163 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7501 4.3718 -1.2410 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8971 3.4577 -2.3227 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2943 2.6769 -3.2732 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6097 2.2447 -3.5680 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0586 1.7886 -0.7252 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3195 1.1562 -2.5709 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2971 -1.0199 -2.5971 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6687 -2.1984 -0.6078 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8970 0.0405 -0.1755 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3198 -0.4919 -0.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4439 -1.3986 -2.7708 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3735 -0.4153 -1.5850 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0298 -3.4756 -1.6904 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4642 -2.7183 -2.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2320 -4.3695 0.8839 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0113 -4.7565 -0.3137 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5887 -4.8591 -0.7050 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7411 -0.6267 -0.1015 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2408 -2.5723 1.7652 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6940 -0.3378 2.8847 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7165 -2.0435 3.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5290 -1.5412 2.4782 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2081 -0.5017 1.2051 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8143 -2.4019 1.0314 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3609 -3.5455 -0.2286 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9533 -3.5460 2.5713 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8295 1.2304 2.5015 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8221 1.0784 0.7350 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9600 2.0462 2.6104 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6293 2.4777 0.9262 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0979 1.0009 0.1340 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4391 1.1708 0.6595 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3842 0.6193 4.1321 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8018 -1.0728 3.5609 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5432 -2.6122 0.3617 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4230 -2.3526 2.1067 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8770 -1.7356 1.2759 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1772 0.4840 -0.6907 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4185 -0.6802 -1.1890 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9300 -2.4729 -1.1709 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7780 -0.0309 -1.9577 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1042 0.0163 3.6989 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8561 -1.0124 1.0222 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8559 -2.2517 -1.8184 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7337 2.2438 -2.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7867 3.3556 0.5686 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9121 3.7787 1.1759 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8142 3.9598 -0.1845 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9678 1.9037 -1.9597 H 0 0 0 0 0 0 0 0 0 0 0 0 11.0637 1.9930 -0.5337 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9753 1.7400 0.9277 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0587 -0.1693 -1.2172 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7420 5.2595 -1.8869 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0063 5.7655 0.7646 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9096 4.6558 -0.7858 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 6 13 14 1 0 12 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 19 21 1 1 16 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 28 30 1 0 30 31 1 0 25 32 1 0 32 33 1 6 32 34 1 0 34 35 1 0 35 36 1 0 22 37 1 1 5 38 1 0 4 39 1 0 3 40 1 0 40 41 1 0 41 42 1 0 42 43 1 0 43 44 1 0 44 45 1 0 45 46 1 0 46 47 1 0 45 48 1 0 44 49 1 0 43 50 1 0 42 51 1 0 7 2 1 0 20 9 1 0 32 22 1 0 48 41 1 0 19 12 1 0 31 26 1 0 35 15 1 0 1 52 1 0 1 53 1 0 1 54 1 0 2 55 1 1 3 56 1 6 4 57 1 6 5 58 1 1 6 59 1 1 9 60 1 1 10 61 1 0 10 62 1 0 11 63 1 0 11 64 1 0 13 65 1 0 13 66 1 0 14 67 1 0 15 68 1 1 16 69 1 1 17 70 1 0 17 71 1 0 18 72 1 0 18 73 1 0 20 74 1 0 20 75 1 0 21 76 1 0 23 77 1 0 23 78 1 0 24 79 1 0 24 80 1 0 25 81 1 6 27 82 1 0 31 83 1 0 31 84 1 0 33 85 1 0 33 86 1 0 33 87 1 0 34 88 1 0 34 89 1 0 35 90 1 6 36 91 1 0 37 92 1 0 38 93 1 0 39 94 1 0 41 95 1 6 42 96 1 1 43 97 1 1 44 98 1 1 45 99 1 6 46100 1 0 46101 1 0 47102 1 0 49103 1 0 50104 1 0 51105 1 0 M END

Standard InCHIKey	YPZVRDVFGRFZHP-PCUDRXQQSA-N
Standard InCHI	InChI=1S/C35H54O16/c1-15-29(51-31-27(43)25(41)24(40)21(12-36)50-31)26(42)28(44)30(48-15)49-17-3-6-33(14-37)23-19(4-7-34(33,45)10-17)35(46)8-5-18(16-9-22(39)47-13-16)32(35,2)11-20(23)38/h9,15,17-21,23-31,36-38,40-46H,3-8,10-14H2,1-2H3/t15-,17+,18-,19-,20-,21-,23-,24-,25-,26+,27-,28-,29-,30+,31+,32-,33+,34+,35+/m1/s1
SMILES	C[C@@H]1[C@H]([C@H]([C@H]([C@@H](O1)O[C@H]1CC[C@]2(CO)[C@@H]3[C@@H](CC[C@@]2(C1)O)[C@]1(CC[C@H](C2=CC(=O)OC2)[C@@]1(C)C[C@H]3O)O)O)O)O[C@H]1[C@@H]([C@@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	730.34	Volume:	689.391 ? Van der Waals volume.
Dense:	1.059	LogP:	-2.168 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.965 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-0.449 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	38.0
TPSA:	265.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	16.0
H-Bond Donor:	10.0	Rings:	7.0
Heavy Atoms:	16.0

MedChem Properties

QED Drug-Likeness Score:	0.095	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.936	Fsp³:	0.914
MCE-18:	141.791 ? 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:	0.556	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.115	Promiscuous compounds:	0.51

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-7.08	MDCK Permeability:	-5.102
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):	0.622
20% Bioavailability (F20%):	0.872	30% Bioavailability (F30%):	0.981
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.534
Plasma Protein Binding (PPB):	27.674%	Volume Distribution (VD):	-0.642
Fu:	72.455% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.828
OATP1B3 inhibitor:	0.127	BCRP inhibitor:	0.0
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.107
HLM stability:	0.0 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

0.065

Half-life (T1/2):

4.605

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.242
Human Hepatotoxicity (H-HT):	0.727	Drug-induced Liver Injury (DILI):	0.559
AMES Toxicity:	0.941	Rat Oral Acute Toxicity:	0.748
Maximum Recommended Daily Dose:	0.995	Skin Sensitization:	1.0
Carcinogencity:	0.594	Eye Corrosion:	0.0
Eye Irritation:	0.0	Respiratory Toxicity:	0.855
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.985
Hematotoxicity:	0.61	Drug-induced Nephrotoxicity:	0.99
Genotoxicity:	0.994	RPMI-8226 Immunitoxicity:	0.907
A549 Cytotoxicity:	0.939	Hek293 Cytotoxicity:	0.988
BCF:	0.534 ? 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:	3.092 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.441 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.556 ? 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
NPO9392	Elaeodendron alluaudianum	Species	Celastraceae	Eukaryota	n.a.	Madagascar Rainforest	n.a.	PMID[19058971]
NPO9392	Elaeodendron alluaudianum	Species	Celastraceae	Eukaryota	n.a.	stem	n.a.	PMID[19058971]
NPO9392	Elaeodendron alluaudianum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9392	Elaeodendron alluaudianum	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21057	Lumbriconereis heteropoda	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO24545	Arctostaphylos columbiana	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23724	Holodiscus discolor	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2497	Pityogenes chalcographus	Species	Curculionidae	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
IC50	2

Activity Type	# Activity
Cell line	2

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
NPT179	Cell line	A2780	Homo sapiens	IC50	=	120.0	nM	PMID[19058971]
NPT466	Cell line	U-937	Homo sapiens	IC50	=	150.0	nM	PMID[19058971]

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 NPC264336 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	16838
0.1-0.2	28064
0.2-0.3	4109
0.3-0.4	669
0.4-0.5	71
0.5-0.6	73
0.6-0.7	23
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8488	Intermediate Similarity	NPC59288
0.764	Intermediate Similarity	NPC32793
0.764	Intermediate Similarity	NPC116075
0.7143	Intermediate Similarity	NPC32177
0.7143	Intermediate Similarity	NPC469756
0.7143	Intermediate Similarity	NPC275901
0.6957	Remote Similarity	NPC236973
0.6897	Remote Similarity	NPC84987
0.6882	Remote Similarity	NPC188234
0.6818	Remote Similarity	NPC157376
0.6818	Remote Similarity	NPC142066
0.6818	Remote Similarity	NPC603972
0.6702	Remote Similarity	NPC475556
0.6702	Remote Similarity	NPC311706
0.6632	Remote Similarity	NPC475629
0.6304	Remote Similarity	NPC83287
0.6264	Remote Similarity	NPC77299
0.6264	Remote Similarity	NPC480906
0.6087	Remote Similarity	NPC5311
0.6061	Remote Similarity	NPC486135
0.6061	Remote Similarity	NPC486137
0.6044	Remote Similarity	NPC99728
0.6044	Remote Similarity	NPC87250
0.6044	Remote Similarity	NPC244402
0.6044	Remote Similarity	NPC50305
0.6022	Remote Similarity	NPC480914
0.6	Remote Similarity	NPC469749
0.6	Remote Similarity	NPC471354
0.6	Remote Similarity	NPC27507
0.5941	Remote Similarity	NPC146857
0.5938	Remote Similarity	NPC480907
0.5914	Remote Similarity	NPC17896
0.5914	Remote Similarity	NPC469755
0.5914	Remote Similarity	NPC284406
0.5914	Remote Similarity	NPC197707
0.5914	Remote Similarity	NPC251866
0.59	Remote Similarity	NPC486143
0.59	Remote Similarity	NPC125077
0.59	Remote Similarity	NPC486142
0.59	Remote Similarity	NPC486149
0.5859	Remote Similarity	NPC486130
0.5849	Remote Similarity	NPC329675
0.5842	Remote Similarity	NPC232785
0.5842	Remote Similarity	NPC486139
0.58	Remote Similarity	NPC486127
0.5784	Remote Similarity	NPC247190
0.5758	Remote Similarity	NPC40749
0.5714	Remote Similarity	NPC486136
0.57	Remote Similarity	NPC480910
0.57	Remote Similarity	NPC480909
0.5684	Remote Similarity	NPC76572
0.5684	Remote Similarity	NPC193382
0.5657	Remote Similarity	NPC30483
0.5657	Remote Similarity	NPC470897
0.5607	Remote Similarity	NPC120390
0.5591	Remote Similarity	NPC158344
0.5566	Remote Similarity	NPC486144
0.5566	Remote Similarity	NPC486145
0.5566	Remote Similarity	NPC486147
0.5566	Remote Similarity	NPC475590
0.5566	Remote Similarity	NPC486148
0.5556	Remote Similarity	NPC194716
0.5545	Remote Similarity	NPC240070
0.5524	Remote Similarity	NPC486132
0.5524	Remote Similarity	NPC486131
0.5521	Remote Similarity	NPC243196
0.5474	Remote Similarity	NPC219085
0.5472	Remote Similarity	NPC486128
0.5464	Remote Similarity	NPC77319
0.5464	Remote Similarity	NPC471351
0.5464	Remote Similarity	NPC471355
0.5463	Remote Similarity	NPC74259
0.5446	Remote Similarity	NPC292467
0.5437	Remote Similarity	NPC208193
0.5392	Remote Similarity	NPC608063
0.5368	Remote Similarity	NPC99620
0.5333	Remote Similarity	NPC329986
0.5333	Remote Similarity	NPC140092
0.5333	Remote Similarity	NPC486146
0.5312	Remote Similarity	NPC309034
0.5306	Remote Similarity	NPC146456
0.5283	Remote Similarity	NPC486138
0.5283	Remote Similarity	NPC276838
0.5273	Remote Similarity	NPC486140
0.5258	Remote Similarity	NPC469750
0.5253	Remote Similarity	NPC9499
0.5253	Remote Similarity	NPC471360
0.5253	Remote Similarity	NPC469751
0.5253	Remote Similarity	NPC471361
0.5253	Remote Similarity	NPC86159
0.5253	Remote Similarity	NPC469752
0.5253	Remote Similarity	NPC469754
0.5253	Remote Similarity	NPC70542
0.5225	Remote Similarity	NPC486133
0.5192	Remote Similarity	NPC610296
0.5135	Remote Similarity	NPC474908
0.5133	Remote Similarity	NPC474423
0.5104	Remote Similarity	NPC474418
0.51	Remote Similarity	NPC471353
0.5048	Remote Similarity	NPC231518
0.5048	Remote Similarity	NPC488944
0.5045	Remote Similarity	NPC475419

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC264336 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6371
0.1-0.2	2681
0.2-0.3	74
0.3-0.4	13
0.4-0.5	7
0.5-0.6	2
0.6-0.7	2
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
0.6304	Remote Similarity	NPD7327	Approved
0.6304	Remote Similarity	NPD7328	Phase 4
0.5914	Remote Similarity	NPD7319	Approved
0.5048	Remote Similarity	NPD8033	Approved

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