NPASS Compound

Natural Product: NPC25906

Natural Product ID	NPC25906
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(4As,6As,6Br,8R,10S,12Ar,14Bs)-8,10-Dihydroxy-2,2,6A,6B,9,9,12A-Heptamethyl-1,3,4,5,6,6A,7,8,8A,10,11,12,13,14B-Tetradecahydropicene-4A-Carboxylic Acid
IUPAC Name	(4aS,6aS,6bR,8R,10S,12aR,14bS)-8,10-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1698617
PubChem CID	23723041
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0001553] Triterpenoids

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 82 86 0 0 0 0 0 0 0 0999 V2000 -4.6636 -0.7538 2.4457 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8314 -1.1673 1.0053 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3642 -2.5947 0.9184 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6896 -0.2836 0.1939 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0969 0.7242 -0.6791 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6354 1.0474 -0.5458 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9677 1.2916 -1.8426 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4954 1.1910 -1.9799 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8512 0.1283 -1.1317 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3357 -1.2038 -1.7090 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4669 0.3440 0.1998 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7418 0.7984 1.1709 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7072 1.1518 1.1041 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3082 1.0954 -0.2430 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7978 0.9428 -0.1303 C 0 0 1 0 0 0 0 0 0 0 0 0 3.4762 1.4467 -1.3830 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3378 1.8510 0.9640 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0547 1.1162 2.0659 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1706 0.2495 1.5802 C 0 0 1 0 0 0 0 0 0 0 0 0 4.5716 -0.7441 0.5911 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4959 -1.0222 -0.5373 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5362 -2.0851 1.3686 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1601 -0.4410 0.2820 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5328 -1.5213 -0.5402 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0734 -1.2714 -0.5862 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6442 0.0597 -1.1591 C 0 0 1 0 0 0 0 0 0 0 0 0 1.0385 0.2184 -2.5996 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1785 -1.8357 -1.6966 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2085 0.9762 0.9975 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9057 0.1164 0.3840 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4591 -1.2388 0.2934 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6045 2.3816 0.1751 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0890 3.4086 -0.3151 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1601 2.5308 1.4437 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0337 0.2459 2.6794 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3116 -1.4584 3.0485 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6291 -0.9598 2.8200 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4393 -2.6568 1.1547 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7614 -3.2778 1.5505 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2402 -2.9107 -0.1384 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3811 -0.9392 -0.4281 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4206 0.2010 0.9118 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7395 1.6551 -0.6433 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2177 0.4047 -1.7594 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4195 0.5640 -2.5840 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2627 2.2889 -2.3006 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0839 2.1845 -1.6400 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2574 1.1341 -3.0496 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2246 -1.0631 -2.3885 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6061 -1.6321 -2.4629 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4439 -1.9903 -0.9688 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1984 0.9520 2.1523 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1942 0.6546 1.9271 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6807 2.2548 1.4009 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1459 2.0726 -0.7921 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6217 0.7500 -2.1798 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9433 2.4050 -1.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5146 1.8409 -1.1357 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6202 2.5222 1.4158 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1376 2.5607 0.5758 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5404 1.9266 2.6891 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4357 0.5619 2.7602 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6170 -0.2425 2.4705 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5819 -0.2962 -1.3281 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5310 -1.0788 -0.0765 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3726 -2.0647 -0.9571 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5625 -2.9283 0.6633 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6070 -2.1162 1.9955 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4276 -2.1569 2.0112 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6330 -0.5657 1.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6426 -2.4591 0.1059 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7496 -1.2107 0.5020 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5850 -2.1578 -0.9557 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2181 -0.0488 -3.3375 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8216 -0.5127 -2.9408 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2711 1.2655 -2.8908 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8316 -2.6821 -2.0449 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1178 1.9022 1.3008 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1643 0.4644 1.4418 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9139 -1.9922 0.8954 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7769 -1.5948 -0.7079 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8125 3.2766 2.0583 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 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 1 6 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 6 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 20 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 6 24 28 1 0 19 29 1 0 11 30 1 0 30 31 1 0 6 32 1 1 32 33 2 0 32 34 1 0 31 2 1 0 30 6 1 0 26 9 1 0 26 14 1 0 23 15 1 0 1 35 1 0 1 36 1 0 1 37 1 0 3 38 1 0 3 39 1 0 3 40 1 0 4 41 1 0 4 42 1 0 5 43 1 0 5 44 1 0 7 45 1 0 7 46 1 0 8 47 1 0 8 48 1 0 10 49 1 0 10 50 1 0 10 51 1 0 12 52 1 0 13 53 1 0 13 54 1 0 14 55 1 0 16 56 1 0 16 57 1 0 16 58 1 0 17 59 1 0 17 60 1 0 18 61 1 0 18 62 1 0 19 63 1 1 21 64 1 0 21 65 1 0 21 66 1 0 22 67 1 0 22 68 1 0 22 69 1 0 23 70 1 0 24 71 1 1 25 72 1 0 25 73 1 0 27 74 1 0 27 75 1 0 27 76 1 0 28 77 1 0 29 78 1 0 30 79 1 1 31 80 1 0 31 81 1 0 34 82 1 0 M END

Standard InCHIKey	KLHSKTMVSOWVLD-FADATJPDSA-N
Standard InCHI	InChI=1S/C30H48O4/c1-25(2)12-14-30(24(33)34)15-13-28(6)18(19(30)16-25)8-9-21-27(5)11-10-22(32)26(3,4)23(27)20(31)17-29(21,28)7/h8,19-23,31-32H,9-17H2,1-7H3,(H,33,34)/t19-,20+,21?,22-,23?,27+,28+,29+,30-/m0/s1
SMILES	CC1(C)CC[C@@]2(CC[C@]3(C)C(=CCC4[C@@]5(C)CC[C@@H](C(C)(C)C5[C@@H](C[C@@]34C)O)O)[C@@H]2C1)C(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	472.36	Volume:	514.542 ? Van der Waals volume.
Dense:	0.918	LogP:	2.941 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.831 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.435 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	27.0
TPSA:	77.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	5.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.397	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.831	Fsp³:	0.9
MCE-18:	108.07 ? 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:	0.653	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.03 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.271	Promiscuous compounds:	0.062

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.308	MDCK Permeability:	-4.971
Pgp-inhibitor:	0.0	Pgp-substrate:	0.201
PAMPA:	1.0 ? 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):	0.001
20% Bioavailability (F20%):	0.628	30% Bioavailability (F30%):	0.035
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.559	MRP1:	0.996
Plasma Protein Binding (PPB):	89.221%	Volume Distribution (VD):	-0.377
Fu:	9.088% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.941	BCRP inhibitor:	0.001
BSEP inhibitor:	0.294

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.014
CYP2C19-inhibitor:	0.905	CYP2C19-substrate:	0.758
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.262
CYP3A4-inhibitor:	0.906	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.274
HLM stability:	0.679 ? 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):

5.489

Half-life (T1/2):

0.837

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.11
Human Hepatotoxicity (H-HT):	0.748	Drug-induced Liver Injury (DILI):	0.223
AMES Toxicity:	0.323	Rat Oral Acute Toxicity:	0.696
Maximum Recommended Daily Dose:	0.656	Skin Sensitization:	0.93
Carcinogencity:	0.873	Eye Corrosion:	0.001
Eye Irritation:	0.219	Respiratory Toxicity:	0.846
Drug-induced Neurotoxicity:	0.098	Ototoxicity:	0.799
Hematotoxicity:	0.271	Drug-induced Nephrotoxicity:	0.681
Genotoxicity:	0.737	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.349	Hek293 Cytotoxicity:	0.262
BCF:	1.57 ? 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:	4.066 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.64 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.964 ? 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
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	Whole plant	n.a.	n.a.	PMID[11141121]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11291	Styrax benzoin	Species	Styracaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20828	Swertia leducii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11291	Styrax benzoin	Species	Styracaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11291	Styrax benzoin	Species	Styracaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20828	Swertia leducii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11291	Styrax benzoin	Species	Styracaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO11291	Styrax benzoin	Species	Styracaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO20828	Swertia leducii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20828	Swertia leducii	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11291	Styrax benzoin	Species	Styracaceae	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
Potency	12

Activity Type	# Activity
Individual protein	10
Others	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT152	Individual protein	Nuclear factor erythroid 2-related factor 2	Homo sapiens	Potency	n.a.	23109.3	nM	PubChem BioAssay data set
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	29092.9	nM	PubChem BioAssay data set
NPT10	Individual protein	Geminin	Homo sapiens	Potency	n.a.	6513.1	nM	PubChem BioAssay data set
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	10000.0	nM	PubChem BioAssay data set
NPT159	Individual protein	Aberrant vpr protein	Human immunodeficiency virus 1	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT446	Individual protein	Rap guanine nucleotide exchange factor 3	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT446	Individual protein	Rap guanine nucleotide exchange factor 3	Homo sapiens	Potency	n.a.	100000.0	nM	PubChem BioAssay data set
NPT478	Individual protein	Ataxin-2	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT535	Individual protein	Parathyroid hormone receptor	Homo sapiens	Potency	n.a.	17782.8	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	39810.7	nM	PubChem BioAssay data set

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 NPC25906 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	24615
0.1-0.2	21881
0.2-0.3	2663
0.3-0.4	416
0.4-0.5	186
0.5-0.6	53
0.6-0.7	28
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC64872
0.8525	High Similarity	NPC130278
0.7778	Intermediate Similarity	NPC290972
0.7619	Intermediate Similarity	NPC480946
0.7619	Intermediate Similarity	NPC130577
0.7619	Intermediate Similarity	NPC142415
0.7619	Intermediate Similarity	NPC102683
0.7273	Intermediate Similarity	NPC139570
0.7273	Intermediate Similarity	NPC291028
0.7231	Intermediate Similarity	NPC307282
0.7164	Intermediate Similarity	NPC118519
0.697	Remote Similarity	NPC270768
0.697	Remote Similarity	NPC59263
0.697	Remote Similarity	NPC210106
0.6765	Remote Similarity	NPC298554
0.6618	Remote Similarity	NPC73489
0.6567	Remote Similarity	NPC198664
0.6471	Remote Similarity	NPC182797
0.6471	Remote Similarity	NPC282616
0.6471	Remote Similarity	NPC275809
0.6471	Remote Similarity	NPC84319
0.6471	Remote Similarity	NPC52021
0.6471	Remote Similarity	NPC52169
0.6471	Remote Similarity	NPC488562
0.6471	Remote Similarity	NPC599947
0.6377	Remote Similarity	NPC110308
0.6301	Remote Similarity	NPC474727
0.6176	Remote Similarity	NPC43686
0.6143	Remote Similarity	NPC106112
0.6143	Remote Similarity	NPC261935
0.6143	Remote Similarity	NPC231063
0.6143	Remote Similarity	NPC282395
0.6143	Remote Similarity	NPC481360
0.6111	Remote Similarity	NPC137072
0.6056	Remote Similarity	NPC228784
0.6056	Remote Similarity	NPC324341
0.6056	Remote Similarity	NPC601810
0.6	Remote Similarity	NPC121798
0.6	Remote Similarity	NPC234346
0.5857	Remote Similarity	NPC474806
0.5857	Remote Similarity	NPC187722
0.5857	Remote Similarity	NPC133579
0.5775	Remote Similarity	NPC37038
0.5775	Remote Similarity	NPC32118
0.5753	Remote Similarity	NPC91010
0.5735	Remote Similarity	NPC604575
0.5694	Remote Similarity	NPC158141
0.5647	Remote Similarity	NPC266365
0.5616	Remote Similarity	NPC202728
0.5616	Remote Similarity	NPC158059
0.5571	Remote Similarity	NPC280654
0.5556	Remote Similarity	NPC51700
0.5556	Remote Similarity	NPC88716
0.5556	Remote Similarity	NPC68160
0.5556	Remote Similarity	NPC606443
0.5479	Remote Similarity	NPC472149
0.5467	Remote Similarity	NPC130520
0.5417	Remote Similarity	NPC473240
0.5405	Remote Similarity	NPC293564
0.5405	Remote Similarity	NPC29765
0.5395	Remote Similarity	NPC222047
0.5352	Remote Similarity	NPC161751
0.5352	Remote Similarity	NPC474972
0.5352	Remote Similarity	NPC600543
0.5342	Remote Similarity	NPC229281
0.5342	Remote Similarity	NPC156981
0.5333	Remote Similarity	NPC474963
0.5281	Remote Similarity	NPC198621
0.5281	Remote Similarity	NPC216940
0.527	Remote Similarity	NPC271614
0.527	Remote Similarity	NPC609452
0.52	Remote Similarity	NPC305464
0.52	Remote Similarity	NPC200752
0.52	Remote Similarity	NPC19376
0.52	Remote Similarity	NPC120840
0.52	Remote Similarity	NPC136697
0.52	Remote Similarity	NPC25848
0.5195	Remote Similarity	NPC296164
0.5185	Remote Similarity	NPC603645
0.5181	Remote Similarity	NPC204407
0.5132	Remote Similarity	NPC191412
0.5132	Remote Similarity	NPC114159
0.5132	Remote Similarity	NPC6818
0.5119	Remote Similarity	NPC283849
0.5119	Remote Similarity	NPC28198
0.5119	Remote Similarity	NPC476123
0.5119	Remote Similarity	NPC606107
0.5067	Remote Similarity	NPC61543
0.5067	Remote Similarity	NPC293048
0.5067	Remote Similarity	NPC225585
0.5067	Remote Similarity	NPC88116
0.5067	Remote Similarity	NPC481314

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC25906 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6743
0.1-0.2	2366
0.2-0.3	36
0.3-0.4	5
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