NPASS Compound

Natural Product: NPC319556

Natural Product ID	NPC319556
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Esulatin K
IUPAC Name	[(1R,2R,3aR,5R,6E,9R,11R,13R,13aS)-1,3a,11,13-tetraacetyloxy-2,5,8,8-tetramethyl-12-methylidene-4-oxo-2-(pyridine-3-carbonyloxy)-1,3,5,9,10,11,13,13a-octahydrocyclopenta[12]annulen-9-yl] pyridine-3-carboxylate
Synonyms	Esulatin K
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1811926
PubChem CID	53359849
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 101104 0 0 0 0 0 0 0 0999 V2000 0.1730 -3.0329 3.1437 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4348 -2.5749 1.7007 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8687 -2.2572 1.1194 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0008 -2.3114 1.7580 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3114 -1.9568 1.0887 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5884 -0.4949 1.3283 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4965 0.4633 1.1190 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9848 0.8198 -0.1836 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8139 1.7768 -0.1350 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9855 2.7935 -0.9644 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3968 1.7190 0.6349 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5410 0.8995 0.6040 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4904 1.3379 -0.5589 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3583 0.2170 -1.5326 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6304 -0.9304 -0.8337 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7806 -0.5448 0.5803 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2642 -1.3659 1.6436 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6008 -0.9536 2.7954 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2535 -0.5437 0.8630 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9745 -1.6851 0.9181 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3573 -2.7319 0.7196 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4601 -1.6997 1.2055 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6221 0.6235 -2.7968 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6395 -0.1903 -1.9531 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5252 0.5944 -2.6252 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2299 1.7755 -2.9346 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8640 0.1266 -3.0276 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7581 0.9172 -3.7087 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9779 0.5066 -4.0733 N 0 0 0 0 0 0 0 0 0 0 0 0 8.4126 -0.7539 -3.7807 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5353 -1.5702 -3.0973 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2745 -1.1641 -2.7136 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7787 1.3781 -0.0019 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5436 2.5193 0.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0895 3.6076 -0.2406 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8845 2.4010 0.7532 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0826 1.7503 2.0249 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0490 2.8011 2.8684 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6234 3.8499 2.4607 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4763 2.7306 4.2690 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8178 -0.0438 -1.2334 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4747 0.0168 -2.4468 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3177 0.9045 -2.7048 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1904 -0.9852 -3.4871 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7267 -0.0625 0.5637 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9399 0.2766 1.1337 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0107 0.1876 2.3877 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0928 0.7158 0.3614 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1066 0.8487 -1.0048 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2171 1.2638 -1.6678 N 0 0 0 0 0 0 0 0 0 0 0 0 -9.3661 1.5679 -1.0230 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3900 1.4465 0.3458 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2606 1.0238 1.0261 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4622 -2.3977 -0.3070 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4243 -2.7703 1.8483 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2613 -2.2173 3.7468 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4861 -3.9000 3.1934 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1513 -3.3900 3.5869 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8410 -3.4449 1.1181 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9278 -1.9947 0.1129 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9791 -2.6130 2.7558 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9648 -0.4634 2.4068 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8300 1.4076 1.6965 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6421 0.1204 1.8378 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8459 1.5379 -0.6041 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2251 3.5586 -1.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8416 2.9053 -1.5743 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8525 2.8182 0.6343 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1859 1.2791 1.5325 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1338 2.3254 -0.9214 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6303 -1.0607 -1.1743 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1797 -1.8491 -1.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8630 -0.8173 0.6682 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5703 -1.5188 2.2780 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9045 -2.6519 0.8469 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0451 0.1162 -3.7011 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6623 1.7206 -2.9062 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5570 0.3098 -2.7640 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4270 1.9282 -3.9491 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4014 -1.0855 -4.0760 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8966 -2.5805 -2.8685 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6102 -1.8374 -2.1750 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6166 2.5444 -0.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0485 1.4770 1.3069 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0878 3.2324 1.4717 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0183 3.6691 4.4608 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4204 2.7114 4.9342 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0484 1.8177 4.4418 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6150 -0.5255 -4.3313 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5942 -1.8412 -3.1497 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1540 -1.3109 -3.9729 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1916 0.6075 -1.5340 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2523 1.9017 -1.5828 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.3076 1.6871 0.8888 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3299 0.9432 2.1147 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1086 -1.6918 -0.9116 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5489 -2.5684 -0.8941 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0144 -3.3826 -0.4044 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4203 -2.4293 2.8841 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3740 -2.4581 1.3735 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2212 -3.8260 1.6772 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 3 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 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 16 19 1 0 19 20 1 0 20 21 2 0 20 22 1 0 14 23 1 0 14 24 1 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 13 33 1 0 33 34 1 0 34 35 2 0 34 36 1 0 11 37 1 0 37 38 1 0 38 39 2 0 38 40 1 0 8 41 1 0 41 42 1 0 42 43 2 0 42 44 1 0 6 45 1 0 45 46 1 0 46 47 2 0 46 48 1 0 48 49 2 0 49 50 1 0 50 51 2 0 51 52 1 0 52 53 2 0 5 54 1 0 5 55 1 0 17 2 1 0 16 12 1 0 32 27 1 0 53 48 1 0 1 56 1 0 1 57 1 0 1 58 1 0 2 59 1 0 3 60 1 0 4 61 1 0 6 62 1 0 7 63 1 0 7 64 1 0 8 65 1 0 10 66 1 0 10 67 1 0 11 68 1 0 12 69 1 0 13 70 1 0 15 71 1 0 15 72 1 0 22 73 1 0 22 74 1 0 22 75 1 0 23 76 1 0 23 77 1 0 23 78 1 0 28 79 1 0 30 80 1 0 31 81 1 0 32 82 1 0 36 83 1 0 36 84 1 0 36 85 1 0 40 86 1 0 40 87 1 0 40 88 1 0 44 89 1 0 44 90 1 0 44 91 1 0 49 92 1 0 51 93 1 0 52 94 1 0 53 95 1 0 54 96 1 0 54 97 1 0 54 98 1 0 55 99 1 0 55100 1 0 55101 1 0 M END

Standard InCHIKey	JNESAYNUYICKCH-WVMGMPMTSA-N
Standard InCHI	InChI=1S/C40H46N2O13/c1-22-14-15-38(7,8)31(53-36(48)28-12-10-16-41-19-28)18-30(50-24(3)43)23(2)33(51-25(4)44)32-35(52-26(5)45)39(9,21-40(32,34(22)47)54-27(6)46)55-37(49)29-13-11-17-42-20-29/h10-17,19-20,22,30-33,35H,2,18,21H2,1,3-9H3/b15-14+/t22-,30-,31-,32+,33+,35-,39-,40-/m1/s1
SMILES	CC1C=CC(C(CC(C(=C)C(C2C(C(CC2(C1=O)OC(=O)C)(C)OC(=O)C3=CN=CC=C3)OC(=O)C)OC(=O)C)OC(=O)C)OC(=O)C4=CN=CC=C4)(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	762.3	Volume:	762.89 ? Van der Waals volume.
Dense:	0.999	LogP:	3.364 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.082 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.028 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	36.0
TPSA:	200.65 ? Topological Polar Surface Area.	H-Bond Acceptor:	15.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	15.0

MedChem Properties

QED Drug-Likeness Score:	0.207	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.8	Fsp³:	0.475
MCE-18:	124.797 ? 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:	0.138	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.081 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.023	Promiscuous compounds:	0.002

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.011	MDCK Permeability:	-4.755
Pgp-inhibitor:	0.696	Pgp-substrate:	0.0
PAMPA:	0.966 ? 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%):	0.001	30% Bioavailability (F30%):	0.016
50% Bioavailability (F50%):	0.097

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	1.0
Plasma Protein Binding (PPB):	91.628%	Volume Distribution (VD):	0.097
Fu:	10.112% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.057
OATP1B3 inhibitor:	0.907	BCRP inhibitor:	0.0
BSEP inhibitor:	0.987

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.992
CYP3A4-inhibitor:	0.223	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

1.365

Half-life (T1/2):

0.925

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.142
Human Hepatotoxicity (H-HT):	0.104	Drug-induced Liver Injury (DILI):	0.989
AMES Toxicity:	0.053	Rat Oral Acute Toxicity:	0.255
Maximum Recommended Daily Dose:	0.576	Skin Sensitization:	0.597
Carcinogencity:	0.695	Eye Corrosion:	0.0
Eye Irritation:	0.004	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.761	Ototoxicity:	0.458
Hematotoxicity:	0.015	Drug-induced Nephrotoxicity:	0.454
Genotoxicity:	0.884	RPMI-8226 Immunitoxicity:	0.064
A549 Cytotoxicity:	0.01	Hek293 Cytotoxicity:	0.15
BCF:	0.857 ? 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:	3.497 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.24 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.798 ? 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]
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]
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]
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	=	7.2	n.a.	PMID[21612217]
NPT668	Individual protein	P-glycoprotein 1	Homo sapiens	Ratio	=	19.8	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	=	0.5	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	7.5	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	1.3	%	PMID[21612217]
NPT165	Cell line	HeLa	Homo sapiens	GI	=	0.6	%	PMID[21612217]
NPT2738	Cell line	Ishikawa	Homo sapiens	GI	=	0.1	%	PMID[21612217]
NPT83	Cell line	MCF7	Homo sapiens	GI	=	21.3	%	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 NPC319556 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	15795
0.1-0.2	32519
0.2-0.3	1338
0.3-0.4	157
0.4-0.5	32
0.5-0.6	10
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9324	High Similarity	NPC40919
0.8272	Intermediate Similarity	NPC470189
0.759	Intermediate Similarity	NPC207531
0.7143	Intermediate Similarity	NPC317191
0.686	Remote Similarity	NPC470190
0.6316	Remote Similarity	NPC78127
0.6	Remote Similarity	NPC325805
0.5843	Remote Similarity	NPC482263
0.573	Remote Similarity	NPC475660
0.5682	Remote Similarity	NPC194769
0.5682	Remote Similarity	NPC272523
0.5444	Remote Similarity	NPC285221
0.5417	Remote Similarity	NPC482258
0.5375	Remote Similarity	NPC49393
0.5269	Remote Similarity	NPC482253
0.5109	Remote Similarity	NPC482254
0.506	Remote Similarity	NPC482404

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC319556 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4434
0.1-0.2	4669
0.2-0.3	46
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