NPASS Compound

Natural Product: NPC470616

Natural Product ID	NPC470616
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Leonurusoleanolide A
IUPAC Name	[(1R,2R,3R,4aR,4bS,7S,8R,10aS,10bR,12aR)-3,7-dihydroxy-1-(hydroxymethyl)-1,1',1',4a,10b-pentamethylspiro[2,3,4,4b,5,7,9,10,10a,11,12,12a-dodecahydrochrysene-8,3'-cyclopentane]-2-yl] (E)-3-(4-hydroxyphenyl)prop-2-enoate
Synonyms	leonurusoleanolide A
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2088294
PubChem CID	70693291
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001295] Hydroxysteroids [CHEMONTID:0003241] 12-hydroxysteroids [CHEMONTID:0003243] 12-beta-hydroxysteroids

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 95100 0 0 0 0 0 0 0 0999 V2000 4.1079 2.3638 -1.2258 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7149 2.2064 -1.0855 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5396 0.8473 -0.4035 C 0 0 2 0 0 0 0 0 0 0 0 0 3.2517 0.9619 0.9105 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2024 -0.1272 -1.3449 C 0 0 1 0 0 0 0 0 0 0 0 0 4.6036 -0.1255 -1.2417 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4631 0.1495 -2.2963 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9834 0.4155 -3.4307 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9183 0.1242 -2.0649 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3754 -0.1566 -0.8709 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7807 -0.1970 -0.5824 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1940 -0.5028 0.7125 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5423 -0.5532 1.0370 C 0 0 0 0 0 0 0 0 0 0 0 0 11.4888 -0.2976 0.0661 C 0 0 0 0 0 0 0 0 0 0 0 0 11.0778 0.0020 -1.2029 C 0 0 0 0 0 0 0 0 0 0 0 0 9.7210 0.0560 -1.5426 C 0 0 0 0 0 0 0 0 0 0 0 0 12.8485 -0.3308 0.3205 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7351 -1.5543 -1.1967 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0912 -2.1972 -2.4116 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2489 -1.6712 -1.1039 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6906 -0.8096 0.0461 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0783 0.5933 -0.3370 C 0 0 1 0 0 0 0 0 0 0 0 0 0.2846 1.6308 0.3939 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1574 1.4623 -0.1181 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6480 0.1398 0.4454 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.7662 -1.0052 0.0852 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1766 -2.1517 1.0203 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6501 -2.2856 1.0451 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5047 -1.4198 0.5392 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0144 -0.1932 -0.1214 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9761 0.9553 -0.0450 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3042 0.4319 -0.5589 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8522 -0.5790 0.4115 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.9631 -1.7346 0.6638 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.2518 -2.2285 1.9512 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3601 0.1172 1.6321 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6347 0.8283 1.1673 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2424 -0.2090 0.2678 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1530 -1.1187 -0.1974 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.2977 -0.9502 1.0930 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9376 0.3761 -0.9271 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8609 0.3678 1.9127 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3374 -1.3506 1.2769 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3376 3.2961 -1.4623 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4405 3.0410 -0.3739 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1918 2.2746 -2.0349 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1242 0.2490 1.0007 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7609 1.9634 1.0580 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5664 0.9048 1.7850 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9323 0.1543 -2.3934 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5373 0.3431 -2.9108 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6377 -0.3642 -0.0820 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4705 -0.7059 1.4863 H 0 0 0 0 0 0 0 0 0 0 0 0 10.9027 -0.7842 2.0191 H 0 0 0 0 0 0 0 0 0 0 0 0 11.7947 0.2071 -1.9855 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4737 0.3003 -2.5705 H 0 0 0 0 0 0 0 0 0 0 0 0 13.2316 0.4726 0.8267 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2993 -2.1267 -0.4320 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5382 -1.8749 -3.1528 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9956 -2.7353 -0.9498 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8181 -1.3547 -2.0762 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7272 0.6835 -1.4173 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3380 1.5467 1.4874 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5946 2.6245 0.0868 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8079 2.2545 0.2441 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0621 1.4245 -1.2279 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1068 -1.3719 -0.9314 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7725 -3.0941 0.6093 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8040 -1.9154 2.0402 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0353 -3.1939 1.5329 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8833 -0.4054 -1.2251 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6372 1.7225 -0.7806 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0623 1.4237 0.9322 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0630 -0.1268 -1.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0469 1.2101 -0.7186 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1510 -2.5842 -0.0269 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8826 -1.6341 2.6497 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6970 0.8858 2.0276 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6211 -0.5645 2.4580 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3048 1.0474 2.0382 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4246 1.7811 0.6824 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3597 -2.1448 0.1720 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0733 -1.1618 -1.3070 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0886 -1.3148 0.3938 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8442 -1.7580 1.6903 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7941 -0.1925 1.7344 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7601 -0.2283 -1.8418 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5904 1.4112 -1.1725 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.0568 0.3784 -0.7950 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9506 0.3524 2.5229 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2487 1.4271 2.0201 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6207 -0.2515 2.3885 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4371 -1.4158 1.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0175 -2.4366 1.3253 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0541 -0.9064 2.2220 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 3 2 1 6 3 4 1 0 3 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 14 17 1 0 5 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 1 0 31 32 1 0 33 32 1 6 33 34 1 0 34 35 1 0 33 36 1 0 36 37 1 0 37 38 1 0 38 39 1 0 38 40 1 0 38 41 1 0 25 42 1 1 21 43 1 1 22 3 1 0 30 25 1 0 39 33 1 0 16 11 1 0 26 21 1 0 34 29 1 0 1 44 1 0 2 45 1 0 2 46 1 0 4 47 1 0 4 48 1 0 4 49 1 0 5 50 1 6 9 51 1 0 10 52 1 0 12 53 1 0 13 54 1 0 15 55 1 0 16 56 1 0 17 57 1 0 18 58 1 1 19 59 1 0 20 60 1 0 20 61 1 0 22 62 1 6 23 63 1 0 23 64 1 0 24 65 1 0 24 66 1 0 26 67 1 6 27 68 1 0 27 69 1 0 28 70 1 0 30 71 1 6 31 72 1 0 31 73 1 0 32 74 1 0 32 75 1 0 34 76 1 6 35 77 1 0 36 78 1 0 36 79 1 0 37 80 1 0 37 81 1 0 39 82 1 0 39 83 1 0 40 84 1 0 40 85 1 0 40 86 1 0 41 87 1 0 41 88 1 0 41 89 1 0 42 90 1 0 42 91 1 0 42 92 1 0 43 93 1 0 43 94 1 0 43 95 1 0 M END

Standard InCHIKey	INOPWOULITWYGE-IBNAELPZSA-N
Standard InCHI	InChI=1S/C37H52O6/c1-33(2)18-19-37(21-33)17-14-26-25(31(37)42)11-12-28-34(26,3)16-15-29-35(28,4)20-27(40)32(36(29,5)22-38)43-30(41)13-8-23-6-9-24(39)10-7-23/h6-11,13,26-29,31-32,38-40,42H,12,14-22H2,1-5H3/b13-8+/t26-,27-,28+,29-,31-,32+,34+,35-,36+,37-/m1/s1
SMILES	OC[C@]1(C)[C@@H](OC(=O)/C=C/c2ccc(cc2)O)[C@H](O)C[C@]2([C@H]1CC[C@@]1([C@@H]2CC=C2[C@H]1CC[C@@]1([C@@H]2O)CCC(C1)(C)C)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	592.38	Volume:	634.092 ? Van der Waals volume.
Dense:	0.934	LogP:	4.603 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.0 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.559 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	34.0
TPSA:	107.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	6.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.183	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.631	Fsp³:	0.703
MCE-18:	199.302 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.932	Fluc inhibitor:	0.989 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.09 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.041 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.158	Promiscuous compounds:	0.138

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.662	MDCK Permeability:	-5.087
Pgp-inhibitor:	0.982	Pgp-substrate:	0.005
PAMPA:	0.984 ? 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%):	0.536	30% Bioavailability (F30%):	0.41
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.036	MRP1:	0.181
Plasma Protein Binding (PPB):	95.135%	Volume Distribution (VD):	0.372
Fu:	5.846% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.927	BCRP inhibitor:	0.044
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.479
CYP2C19-inhibitor:	0.013	CYP2C19-substrate:	0.992
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.006
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.012
CYP3A4-inhibitor:	0.004	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.546 ? 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):

7.619

Half-life (T1/2):

1.169

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.137
Human Hepatotoxicity (H-HT):	0.553	Drug-induced Liver Injury (DILI):	0.343
AMES Toxicity:	0.259	Rat Oral Acute Toxicity:	0.105
Maximum Recommended Daily Dose:	0.52	Skin Sensitization:	0.928
Carcinogencity:	0.642	Eye Corrosion:	0.001
Eye Irritation:	0.226	Respiratory Toxicity:	0.327
Drug-induced Neurotoxicity:	0.062	Ototoxicity:	0.718
Hematotoxicity:	0.174	Drug-induced Nephrotoxicity:	0.822
Genotoxicity:	0.446	RPMI-8226 Immunitoxicity:	0.044
A549 Cytotoxicity:	0.133	Hek293 Cytotoxicity:	0.498
BCF:	1.033 ? 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:	4.102 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.859 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.106 ? 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
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[22703163]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[24328283]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	aerial part	n.a.	PMID[24704554]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32935986]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23548	Leonurus heterophyllus	Species	Lamiaceae	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
Activity	3
IC50	5

Activity Type	# Activity
Cell line	6
Non-molecular	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
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	41.9	um	PMID[7699697]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	33.5	um	PMID[26814680]
NPT681	Cell line	PC-12	Rattus norvegicus	Activity	=	27.6	um	PMID[26689485]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[15497938]
NPT15	Cell line	Jurkat	Homo sapiens	IC50	>	10000.0	nM	PMID[15497938]
NPT1229	Cell line	Huh-7	Homo sapiens	IC50	>	10000.0	nM	DOI[10.6019/CHEMBL1201861]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[24328283]

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 NPC470616 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	7196
0.1-0.2	37129
0.2-0.3	5178
0.3-0.4	311
0.4-0.5	28
0.5-0.6	11
0.6-0.7	1
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC470617
0.8313	Intermediate Similarity	NPC470618
0.8313	Intermediate Similarity	NPC470619
0.6742	Remote Similarity	NPC26045
0.5657	Remote Similarity	NPC178093
0.56	Remote Similarity	NPC324798
0.56	Remote Similarity	NPC479742
0.53	Remote Similarity	NPC605663
0.5098	Remote Similarity	NPC304110
0.5098	Remote Similarity	NPC25491
0.5098	Remote Similarity	NPC27518
0.5098	Remote Similarity	NPC611516
0.5096	Remote Similarity	NPC479745
0.5052	Remote Similarity	NPC139243
0.5052	Remote Similarity	NPC116742

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC470616 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4195
0.1-0.2	4880
0.2-0.3	74
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