NPASS Compound

Natural Product: NPC40919

Natural Product ID	NPC40919
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2Alpha,3Beta,5Alpha,7Beta,15Beta-Pentaacetoxy-9Alpha-Nicotinoyloxyjatropha-6(17),11-Dien-14-One
IUPAC Name	[(1R,2R,3aR,5R,6E,9R,11R,13R,13aS)-1,2,3a,11,13-pentaacetyloxy-2,5,8,8-tetramethyl-12-methylidene-4-oxo-1,3,5,9,10,11,13,13a-octahydrocyclopenta[12]annulen-9-yl] pyridine-3-carboxylate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1812479
PubChem CID	10122831
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001551] Diterpenoids [CHEMONTID:0002877] Jatrophane and cyclojatrophane diterpenoids

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 95 97 0 0 0 0 0 0 0 0999 V2000 3.1088 1.1046 5.2722 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1895 0.4617 4.2767 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5445 -0.5737 4.5896 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0243 0.9747 3.0088 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1428 0.3778 2.0220 C 0 0 2 0 0 0 0 0 0 0 0 0 1.9338 -0.3331 0.9894 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9553 0.4450 0.2282 C 0 0 1 0 0 0 0 0 0 0 0 0 3.7613 -0.6412 -0.3910 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0257 -0.9236 0.0083 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5137 -0.2319 0.9427 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7690 -1.9943 -0.6372 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0508 -2.3513 -0.2353 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7474 -3.3598 -0.8632 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1732 -4.0506 -1.9270 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9419 -3.7012 -2.3065 N 0 0 0 0 0 0 0 0 0 0 0 0 5.2479 -2.7057 -1.6908 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6512 1.3036 -0.8771 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9025 2.0561 -1.3095 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4208 0.3624 -2.1166 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5346 2.2283 -0.9841 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4300 2.0802 -1.6692 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7149 3.0141 -1.7829 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8211 2.4878 -0.9742 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3920 3.3366 -0.2559 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3570 1.1513 -0.8648 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.5011 0.2630 0.0751 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.3011 0.8808 1.3621 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0601 1.2769 1.7995 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1957 2.5789 2.0104 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7433 0.0185 2.4455 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7407 0.4535 3.3286 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2268 1.5863 3.1393 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1518 -0.4532 4.4279 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3342 -0.9724 0.0496 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5362 -0.9676 0.7517 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8531 -2.0886 1.5438 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0645 -3.0656 1.6179 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1460 -2.1234 2.3074 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6851 -1.1022 -1.4645 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5427 0.2918 -2.0334 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0801 -1.6645 -1.6036 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7761 -2.0304 -1.9983 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7551 -2.4306 -3.3036 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5885 -1.9690 -4.1330 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7180 -3.4235 -3.7045 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6405 1.1961 -0.1989 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6487 1.9282 -0.7705 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4267 2.5375 -1.8438 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0212 2.0288 -0.1593 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0324 3.4332 -3.1867 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9071 1.5944 4.7161 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5408 0.2997 5.8905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5495 1.7698 5.9449 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7333 -0.5393 2.6584 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5258 -1.1134 1.6000 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3576 -1.0412 0.3553 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6665 0.8533 0.9499 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4591 -1.7956 0.5903 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7621 -3.6372 -0.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7377 -4.8450 -2.4124 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2425 -2.4655 -2.0503 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7637 1.3785 -1.4220 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7492 2.5953 -2.2627 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1489 2.8274 -0.5430 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3576 -0.1880 -2.3176 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6534 -0.3854 -1.8494 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1292 0.9180 -2.9940 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6546 3.1414 -0.4196 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2557 1.1758 -2.2940 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4180 4.0246 -1.3035 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5653 -0.0009 -0.4729 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9908 1.7969 1.4197 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1461 2.9533 2.3562 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6012 3.2884 1.8537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2611 -0.4469 4.5292 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6626 -0.1474 5.3865 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8514 -1.5047 4.2129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7574 -1.8849 0.3290 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5727 -1.1128 2.4172 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9676 -2.6219 3.2776 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8696 -2.7435 1.7660 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5372 0.4727 -2.5434 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7392 0.2120 -2.7718 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0664 -2.7718 -1.5686 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7086 -1.3433 -0.7295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5853 -1.3649 -2.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6046 -3.5143 -4.7899 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2449 -3.1050 -3.2205 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0060 -4.3877 -3.2054 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4109 3.0247 -0.4408 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9737 1.9675 0.9299 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7060 1.2954 -0.6343 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7143 2.6327 -3.9212 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4507 4.3320 -3.5204 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0907 3.7067 -3.3336 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 7 17 1 0 17 18 1 0 17 19 1 0 17 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 27 30 1 0 30 31 1 0 31 32 2 0 31 33 1 0 26 34 1 0 34 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 34 39 1 0 39 40 1 0 39 41 1 0 39 42 1 6 42 43 1 0 43 44 2 0 43 45 1 0 25 46 1 1 46 47 1 0 47 48 2 0 47 49 1 0 22 50 1 0 28 5 1 0 16 11 1 0 40 25 1 0 1 51 1 0 1 52 1 0 1 53 1 0 5 54 1 1 6 55 1 0 6 56 1 0 7 57 1 1 12 58 1 0 13 59 1 0 14 60 1 0 16 61 1 0 18 62 1 0 18 63 1 0 18 64 1 0 19 65 1 0 19 66 1 0 19 67 1 0 20 68 1 0 21 69 1 0 22 70 1 1 26 71 1 6 27 72 1 6 29 73 1 0 29 74 1 0 33 75 1 0 33 76 1 0 33 77 1 0 34 78 1 1 38 79 1 0 38 80 1 0 38 81 1 0 40 82 1 0 40 83 1 0 41 84 1 0 41 85 1 0 41 86 1 0 45 87 1 0 45 88 1 0 45 89 1 0 49 90 1 0 49 91 1 0 49 92 1 0 50 93 1 0 50 94 1 0 50 95 1 0 M END

Standard InCHIKey	MBIDOILZBVMYQI-ALCXGGQDSA-N
Standard InCHI	InChI=1S/C36H45NO13/c1-19-13-14-34(8,9)28(48-33(44)26-12-11-15-37-17-26)16-27(45-21(3)38)20(2)30(46-22(4)39)29-32(47-23(5)40)35(10,49-24(6)41)18-36(29,31(19)43)50-25(7)42/h11-15,17,19,27-30,32H,2,16,18H2,1,3-10H3/b14-13+/t19-,27-,28-,29+,30+,32-,35-,36-/m1/s1
SMILES	CC(=O)O[C@@H]1C[C@@H](OC(=O)c2cccnc2)C(C)(C)/C=C/[C@H](C(=O)[C@@]2([C@@H]([C@H](C1=C)OC(=O)C)[C@@H](OC(=O)C)[C@](C2)(C)OC(=O)C)OC(=O)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	699.29	Volume:	699.175 ? Van der Waals volume.
Dense:	1.0	LogP:	2.317 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.575 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.051 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	13.0	Rigid Bonds:	30.0
TPSA:	187.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.227	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.734	Fsp³:	0.556
MCE-18:	111.964 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.656	Fluc inhibitor:	0.006 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.012 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.025	Promiscuous compounds:	0.09

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.098	MDCK Permeability:	-4.763
Pgp-inhibitor:	1.0	Pgp-substrate:	0.003
PAMPA:	0.419 ? 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):	0.0
20% Bioavailability (F20%):	0.963	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	1.0
Plasma Protein Binding (PPB):	84.1%	Volume Distribution (VD):	-0.215
Fu:	14.845% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.945	BCRP inhibitor:	0.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.001
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:	0.001	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

3.765

Half-life (T1/2):

0.544

ADMET: Toxicity

hERG Blockers:	0.002	hERG Blockers (10um):	0.019
Human Hepatotoxicity (H-HT):	0.4	Drug-induced Liver Injury (DILI):	0.99
AMES Toxicity:	0.595	Rat Oral Acute Toxicity:	0.167
Maximum Recommended Daily Dose:	0.253	Skin Sensitization:	0.996
Carcinogencity:	0.718	Eye Corrosion:	0.0
Eye Irritation:	0.027	Respiratory Toxicity:	0.021
Drug-induced Neurotoxicity:	0.263	Ototoxicity:	0.33
Hematotoxicity:	0.333	Drug-induced Nephrotoxicity:	0.941
Genotoxicity:	0.999	RPMI-8226 Immunitoxicity:	0.124
A549 Cytotoxicity:	0.335	Hek293 Cytotoxicity:	0.248
BCF:	0.651 ? 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:	3.477 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.221 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.889 ? 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
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21612217]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21612217]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27203291]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27447736]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32233482]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28219	Euphorbia peplus	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3099	Euphorbia esula	Species	Euphorbiaceae	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
Ratio	2
GI	6

Activity Type	# Activity
Cell line	6
Individual protein	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	1.7	n.a.	PMID[21612217]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	2.3	n.a.	PMID[21612217]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT165	Cell line	HeLa	Homo sapiens	GI	=	13.9	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	8.1	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	20.3	%	PMID[21612217]
NPT165	Cell line	HeLa	Homo sapiens	GI	=	17.9	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	13.9	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	36.3	%	PMID[21612217]

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 NPC40919 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	15389
0.1-0.2	32907
0.2-0.3	1349
0.3-0.4	160
0.4-0.5	32
0.5-0.6	14
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9324	High Similarity	NPC319556
0.8846	High Similarity	NPC470189
0.7262	Intermediate Similarity	NPC207531
0.7229	Intermediate Similarity	NPC317191
0.6941	Remote Similarity	NPC470190
0.6849	Remote Similarity	NPC78127
0.5909	Remote Similarity	NPC482263
0.5862	Remote Similarity	NPC285221
0.5844	Remote Similarity	NPC49393
0.5698	Remote Similarity	NPC325805
0.5506	Remote Similarity	NPC482254
0.55	Remote Similarity	NPC482404
0.5495	Remote Similarity	NPC482253
0.5474	Remote Similarity	NPC482258
0.5444	Remote Similarity	NPC475660
0.5393	Remote Similarity	NPC194769
0.5393	Remote Similarity	NPC272523
0.5176	Remote Similarity	NPC471757
0.5119	Remote Similarity	NPC482403
0.5062	Remote Similarity	NPC470192

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC40919 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4334
0.1-0.2	4777
0.2-0.3	38
0.3-0.4	1
0.4-0.5	0
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	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
		NPD

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