NPASS Compound

Natural Product: NPC184624

Natural Product ID	NPC184624
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Tuberculatin
IUPAC Name	9-(1,3-benzodioxol-5-yl)-4-[(2S,3R,4R)-3,4-dihydroxy-4-(hydroxymethyl)oxolan-2-yl]oxy-6,7-dimethoxy-3H-benzo[f][2]benzofuran-1-one
Synonyms	Tuberculatin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL471889
PubChem CID	10391676
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001511] Lignan glycosides

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 61 66 0 0 0 0 0 0 0 0999 V2000 -3.9364 3.4930 -0.6242 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5498 3.6976 -0.8015 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6432 2.6595 -0.5858 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1122 1.4274 -0.1967 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2088 0.4041 0.0152 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1624 0.5644 -0.1482 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6034 1.7907 -0.5334 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2941 2.8293 -0.7501 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1704 4.0793 -1.1438 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5530 4.3316 -1.3342 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0434 -0.4678 0.0666 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4972 -1.6766 0.4538 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1352 -2.9637 0.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1189 -3.8498 1.0980 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1003 -3.2175 1.0251 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2159 -3.7051 1.2584 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8527 -1.8497 0.6188 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7462 -0.8038 0.4015 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1717 -1.0067 0.5811 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7634 -0.7865 1.7979 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1292 -0.9975 1.9081 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9123 -1.4168 0.8528 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3153 -1.6385 -0.3730 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9428 -1.4239 -0.4742 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2666 -2.0529 -1.2988 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4223 -2.3539 -0.5433 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2635 -1.6985 0.6882 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3983 -0.3488 -0.0827 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3187 0.0194 0.9163 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3272 -1.0829 1.1110 C 0 0 1 0 0 0 0 0 0 0 0 0 5.5730 -0.4802 0.5152 C 0 0 1 0 0 0 0 0 0 0 0 0 5.6613 -0.6808 -0.9817 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5126 -0.2385 -1.6276 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3204 0.9874 0.7744 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9630 1.1639 0.5430 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7269 -0.9220 1.1576 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5231 -1.2406 2.4822 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4523 4.4671 -0.8124 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3378 2.6902 -1.2559 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1083 3.2299 0.4591 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1722 1.2790 -0.0635 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6526 1.9514 -0.6713 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9459 3.5214 -1.9722 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1053 4.4040 -0.3850 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6529 5.3174 -1.8376 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6868 -3.3177 -0.1527 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8987 -2.8487 1.5732 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2066 -0.4544 2.6756 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6056 -0.8268 2.8633 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5127 -1.6135 -1.4691 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5289 -3.4277 -0.3613 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3503 -2.0061 -1.0596 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7849 0.2481 1.8882 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0294 -2.0279 0.6184 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7809 -1.7571 -1.2451 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5090 -0.0904 -1.3671 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7199 0.3959 -2.3803 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5081 1.1771 1.8452 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9558 1.6458 0.1741 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9858 -1.7674 0.7441 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2969 -0.7343 2.8250 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 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 23 25 1 0 25 26 1 0 26 27 1 0 11 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 31 34 1 0 34 35 1 0 31 36 1 1 30 37 1 0 8 3 1 0 17 12 1 0 24 19 1 0 35 29 1 0 18 5 1 0 27 22 1 0 1 38 1 0 1 39 1 0 1 40 1 0 4 41 1 0 7 42 1 0 10 43 1 0 10 44 1 0 10 45 1 0 13 46 1 0 13 47 1 0 20 48 1 0 21 49 1 0 24 50 1 0 26 51 1 0 26 52 1 0 29 53 1 1 30 54 1 6 32 55 1 0 32 56 1 0 33 57 1 0 34 58 1 0 34 59 1 0 36 60 1 0 37 61 1 0 M END

Standard InCHIKey	XIARCTMJGANPJU-AYRHNUGRSA-N
Standard InCHI	InChI=1S/C26H24O11/c1-31-17-6-13-14(7-18(17)32-2)22(37-25-23(28)26(30,9-27)10-34-25)15-8-33-24(29)21(15)20(13)12-3-4-16-19(5-12)36-11-35-16/h3-7,23,25,27-28,30H,8-11H2,1-2H3/t23-,25-,26+/m0/s1
SMILES	COc1cc2c(cc1OC)c(c1COC(=O)c1c2c1ccc2c(c1)OCO2)O[C@H]1[C@@H]([C@@](CO)(CO1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	512.13	Volume:	479.878 ? Van der Waals volume.
Dense:	1.067	LogP:	2.215 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.386 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.85 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	31.0
TPSA:	142.37 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	3.0	Rings:	6.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.416	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.022	Fsp³:	0.346
MCE-18:	117.0 ? 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:	0.602	Fluc inhibitor:	0.213 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.744 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.389 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.023	Promiscuous compounds:	0.689

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.201	MDCK Permeability:	-4.659
Pgp-inhibitor:	0.003	Pgp-substrate:	0.069
PAMPA:	0.895 ? 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):	0.05
20% Bioavailability (F20%):	0.308	30% Bioavailability (F30%):	0.012
50% Bioavailability (F50%):	0.969

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.118	MRP1:	0.733
Plasma Protein Binding (PPB):	97.238%	Volume Distribution (VD):	-0.008
Fu:	3.157% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.996
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.41
BSEP inhibitor:	0.982

ADMET: Metabolism

CYP1A2-inhibitor:	0.289	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.438	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.397	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.885
CYP3A4-inhibitor:	0.433	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.022
HLM stability:	0.002 ? 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):

2.847

Half-life (T1/2):

1.711

ADMET: Toxicity

hERG Blockers:	0.107	hERG Blockers (10um):	0.338
Human Hepatotoxicity (H-HT):	0.976	Drug-induced Liver Injury (DILI):	0.992
AMES Toxicity:	0.982	Rat Oral Acute Toxicity:	0.337
Maximum Recommended Daily Dose:	0.844	Skin Sensitization:	1.0
Carcinogencity:	0.979	Eye Corrosion:	0.0
Eye Irritation:	0.021	Respiratory Toxicity:	0.067
Drug-induced Neurotoxicity:	0.842	Ototoxicity:	0.912
Hematotoxicity:	0.941	Drug-induced Nephrotoxicity:	0.992
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.474
A549 Cytotoxicity:	0.852	Hek293 Cytotoxicity:	0.874
BCF:	1.308 ? 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:	3.725 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.173 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.794 ? 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
NPO13775	Polygala amarella	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10395523]
NPO16045	Justicia procumbens	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11908984]
NPO18042	Geranium nepalense	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23006989]
NPO16045	Justicia procumbens	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3734816]
NPO16045	Justicia procumbens	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8988600]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO24192	Piptoporus australiensis	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22728	Haplophyllum patavinum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO169	Ruta tuberculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24094	Pelargonium reniforme	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16045	Justicia procumbens	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23659	Rostellularia procumbens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13775	Polygala amarella	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24448	Haplopappus ciliatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18042	Geranium nepalense	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23325	Doris verrucosa	Species	Dorididae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18042	Geranium nepalense	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23659	Rostellularia procumbens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO22728	Haplophyllum patavinum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO169	Ruta tuberculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18042	Geranium nepalense	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22728	Haplophyllum patavinum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23659	Rostellularia procumbens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO13775	Polygala amarella	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24094	Pelargonium reniforme	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23659	Rostellularia procumbens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO169	Ruta tuberculata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23659	Rostellularia procumbens	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO16045	Justicia procumbens	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13775	Polygala amarella	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23835	Swertia angustifolia	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24448	Haplopappus ciliatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24192	Piptoporus australiensis	Species	Fomitopsidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18042	Geranium nepalense	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO796	Diphasiastrum alpinum	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24094	Pelargonium reniforme	Species	Geraniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20023	Uncaria gambier	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23369	Hertia intermedia	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25670	Aspergillus foveolatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19177	Euphorbia franckiana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23325	Doris verrucosa	Species	Dorididae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22467	Kippistia suaedifolia	Species	Asteraceae	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
ED50	7
Inhibition	2

Activity Type	# Activity
Cell line	7
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
NPT2245	Cell line	SiHa	Homo sapiens	ED50	=	1.2	10'-1 ug/ml	PMID[11908984]
NPT65	Cell line	HepG2	Homo sapiens	ED50	=	4.0	10'-2 ug/ml	PMID[11908984]
NPT83	Cell line	MCF7	Homo sapiens	ED50	=	9.7	10'-1 ug/ml	PMID[11908984]
NPT139	Cell line	HT-29	Homo sapiens	ED50	=	2.9	10'-1 ug/ml	PMID[11908984]
NPT393	Cell line	HCT-116	Homo sapiens	ED50	=	2.8	10'-1 ug/ml	PMID[11908984]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	16.9	%	PMID[11908984]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	-225.8	%	PMID[11908984]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	1.4	10'-2 ug/ml	PMID[11908984]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	=	9.0	10'-2 ug/ml	PMID[11908984]

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 NPC184624 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	20910
0.1-0.2	28036
0.2-0.3	858
0.3-0.4	11
0.4-0.5	12
0.5-0.6	7
0.6-0.7	16
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
0.7821	Intermediate Similarity	NPC474075
0.7821	Intermediate Similarity	NPC483381
0.7317	Intermediate Similarity	NPC20114
0.7143	Intermediate Similarity	NPC471921
0.7108	Intermediate Similarity	NPC129930
0.7059	Intermediate Similarity	NPC471922
0.7042	Intermediate Similarity	NPC239113
0.6988	Remote Similarity	NPC114550
0.6988	Remote Similarity	NPC312006
0.6988	Remote Similarity	NPC602979
0.6977	Remote Similarity	NPC471920
0.686	Remote Similarity	NPC292712
0.6813	Remote Similarity	NPC35266
0.6806	Remote Similarity	NPC19600
0.6452	Remote Similarity	NPC167045
0.6452	Remote Similarity	NPC114120
0.6395	Remote Similarity	NPC473531
0.6373	Remote Similarity	NPC286301
0.6373	Remote Similarity	NPC313063
0.6364	Remote Similarity	NPC471923
0.6351	Remote Similarity	NPC115123
0.6162	Remote Similarity	NPC161609
0.6146	Remote Similarity	NPC275690
0.5895	Remote Similarity	NPC473697
0.5844	Remote Similarity	NPC78944
0.5641	Remote Similarity	NPC15212
0.5185	Remote Similarity	NPC22130
0.5125	Remote Similarity	NPC299820
0.5062	Remote Similarity	NPC143328
0.5059	Remote Similarity	NPC196771

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC184624 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5022
0.1-0.2	4106
0.2-0.3	21
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