NPASS Compound

Natural Product: NPC254433

Natural Product ID	NPC254433
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LUXDHEOYGQPBDS-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	87579315
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002650] Diarylheptanoids [CHEMONTID:0002651] Linear diarylheptanoids [CHEMONTID:0000356] Curcuminoids

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 65 68 0 0 0 0 0 0 0 0999 V2000 6.9548 0.1627 -1.8363 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5570 -0.0963 -1.9605 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6764 0.7260 -1.3189 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1266 1.7936 -0.5671 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2233 2.6163 0.0762 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8729 2.3786 -0.0272 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4074 1.3300 -0.7641 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9550 1.0257 -0.8806 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5212 0.0603 0.1981 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8748 -0.3598 0.1777 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2741 -1.3482 -0.7196 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3190 -2.1498 -1.4711 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0042 -3.4684 -0.8665 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7751 -3.6141 0.2389 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0924 -4.8703 0.7873 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5985 -5.9944 0.1748 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1799 -5.8349 -0.9429 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4942 -4.6163 -1.4855 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8961 -7.2444 0.6966 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6184 -1.7488 -0.8303 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5571 -1.1688 -0.0443 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2293 -0.1940 0.8595 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8629 0.1980 0.9522 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6134 1.2930 1.8954 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7794 2.6400 1.2558 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6911 3.7301 2.0906 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8980 5.0128 1.5523 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1835 5.1935 0.2282 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2618 4.0919 -0.5653 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0618 2.8246 -0.0613 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3888 6.4948 -0.2675 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1338 0.3702 1.6222 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2983 0.6342 2.1458 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0062 -2.7258 -1.7280 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3127 0.4897 -1.4214 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3160 -0.0382 -0.8135 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4526 -0.4763 -2.6096 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0979 1.2202 -2.1108 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1964 2.0118 -0.4604 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5387 3.4728 0.6827 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1238 3.0087 0.4649 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7889 0.5743 -1.8612 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4047 1.9846 -0.8964 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7435 0.4692 1.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2716 -0.7733 0.1065 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6668 -1.6826 -1.6670 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7767 -2.3161 -2.4899 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2000 -2.7942 0.7939 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7148 -4.9112 1.6734 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5638 -6.7308 -1.4202 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1072 -4.5374 -2.3795 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2554 -7.9884 0.8415 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6037 -1.5068 -0.1523 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3629 1.2579 2.7442 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6448 1.3018 2.3869 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4676 3.6457 3.1494 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8196 5.8437 2.2483 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4868 4.2285 -1.6195 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1279 1.9483 -0.7337 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3363 6.6567 -0.6408 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2208 0.4746 1.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5245 0.1508 3.1534 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3715 1.7492 2.4101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5958 -3.5213 -1.4497 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9911 -0.3540 -2.0163 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 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 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 16 19 1 0 11 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 28 31 1 0 22 32 1 0 32 33 1 0 20 34 1 0 7 35 2 0 35 3 1 0 23 10 2 0 30 25 1 0 18 13 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 5 40 1 0 6 41 1 0 8 42 1 0 8 43 1 0 9 44 1 0 9 45 1 0 12 46 1 0 12 47 1 0 14 48 1 0 15 49 1 0 17 50 1 0 18 51 1 0 19 52 1 0 21 53 1 0 24 54 1 0 24 55 1 0 26 56 1 0 27 57 1 0 29 58 1 0 30 59 1 0 31 60 1 0 33 61 1 0 33 62 1 0 33 63 1 0 34 64 1 0 35 65 1 0 M END

Standard InCHIKey	LUXDHEOYGQPBDS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C30H30O5/c1-34-25-5-3-4-20(16-25)10-15-26-27(17-21-6-11-23(31)12-7-21)29(33)19-30(35-2)28(26)18-22-8-13-24(32)14-9-22/h3-9,11-14,16,19,31-33H,10,15,17-18H2,1-2H3
SMILES	COc1cccc(CCc2c(Cc3ccc(cc3)O)c(cc(c2Cc2ccc(cc2)O)OC)O)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	470.21	Volume:	505.524 ? Van der Waals volume.
Dense:	0.93	LogP:	4.334 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.729 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.378 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	24.0
TPSA:	79.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.289	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.491	Fsp³:	0.2
MCE-18:	23.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.079 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.611 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.62 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.344	Promiscuous compounds:	0.099

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.962	MDCK Permeability:	-4.77
Pgp-inhibitor:	0.077	Pgp-substrate:	0.089
PAMPA:	0.124 ? 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):	0.098
20% Bioavailability (F20%):	0.656	30% Bioavailability (F30%):	0.781
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.312
Plasma Protein Binding (PPB):	98.021%	Volume Distribution (VD):	0.585
Fu:	2.169% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.965
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.211
BSEP inhibitor:	0.997

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.688
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.998
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.131
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.188	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.002	CYP2C8-inhibitor:	1.0
HLM stability:	0.997 ? 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):

8.354

Half-life (T1/2):

1.237

ADMET: Toxicity

hERG Blockers:	0.761	hERG Blockers (10um):	0.956
Human Hepatotoxicity (H-HT):	0.582	Drug-induced Liver Injury (DILI):	0.063
AMES Toxicity:	0.397	Rat Oral Acute Toxicity:	0.072
Maximum Recommended Daily Dose:	0.84	Skin Sensitization:	0.944
Carcinogencity:	0.225	Eye Corrosion:	0.003
Eye Irritation:	0.745	Respiratory Toxicity:	0.873
Drug-induced Neurotoxicity:	0.514	Ototoxicity:	0.292
Hematotoxicity:	0.064	Drug-induced Nephrotoxicity:	0.176
Genotoxicity:	0.464	RPMI-8226 Immunitoxicity:	0.07
A549 Cytotoxicity:	0.691	Hek293 Cytotoxicity:	0.968
BCF:	1.695 ? 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:	5.521 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.2 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.927 ? 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
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1402962]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15686910]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921416]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	subtidal zone (0-2 m) off the southwestern shore of Jeju Island, Korea	2003-Apr	PMID[18817444]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19006667]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21377877]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	Fibrous Roots	n.a.	n.a.	PMID[25760525]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Flower Buds	n.a.	n.a.	PMID[26977531]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	Rhizomes	n.a.	n.a.	PMID[27525452]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28720331]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31415170]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34770801]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36985392]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37836118]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39684253]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39699537]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8904847]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Stem	n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Bark	n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	Essential Oil	n.a.	n.a.	Database[FooDB]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO10780	Bletilla striata	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8787	Ariocarpus scapharostrus	Species	Cactaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24091	Pleione formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7428	Bletilla formosana	Species	Orchidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3987	Syzygium aromaticum	Species	Myrtaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15591	Tolpis webbii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11479	Sargassum siliquastrum	Species	Sargassaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10780	Bletilla striata	Species	Orchidaceae	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
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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6300.0	nM	PMID[27525452]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4200.0	nM	PMID[27525452]

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 NPC254433 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	25315
0.1-0.2	20634
0.2-0.3	3701
0.3-0.4	181
0.4-0.5	20
0.5-0.6	6
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	Natural Product ID
0.7679	Intermediate Similarity	NPC254000
0.5849	Remote Similarity	NPC75440
0.5556	Remote Similarity	NPC215588
0.5238	Remote Similarity	NPC113495
0.5161	Remote Similarity	NPC210881
0.5088	Remote Similarity	NPC53906
0.5077	Remote Similarity	NPC673

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC254433 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4503
0.1-0.2	4473
0.2-0.3	172
0.3-0.4	2
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