NPASS Compound

Natural Product: NPC64081

Natural Product ID	NPC64081
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(20S,24S)-Epoxydammarane-3,12,25-Triol
IUPAC Name	(3S,5R,8R,9R,10R,12R,13R,14R,17S)-17-[(2S,5S)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,12-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL466363
PubChem CID	12314836
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

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 86 90 0 0 0 0 0 0 0 0999 V2000 6.2163 0.0565 0.4712 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2344 1.0451 -0.0952 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5348 2.3819 0.6044 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8146 0.7315 0.1850 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5265 0.4864 1.6372 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0593 0.5167 1.8743 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2499 -0.3249 0.9278 C 0 0 2 0 0 0 0 0 0 0 0 0 1.2266 -1.7286 1.4667 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7408 -0.2706 -0.4942 C 0 0 2 0 0 0 0 0 0 0 0 0 0.9594 -1.1982 -1.3508 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5092 -1.0785 -1.1950 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.0177 -0.8171 0.1711 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3157 -0.1355 0.3091 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3004 0.2873 1.7811 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8342 0.3659 2.1794 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1336 0.2147 0.8960 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2375 1.5343 0.1416 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5648 -0.9045 0.0901 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7168 -2.0865 1.0215 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8374 -1.3421 -1.3111 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2717 -0.8157 -1.5126 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1063 0.4944 -0.7284 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.4264 1.1681 -0.4977 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0072 1.7782 -1.7292 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3689 0.1875 0.1678 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2081 2.1976 0.4244 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6148 -0.0244 0.4666 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0511 -2.3226 -1.6066 O 0 0 0 0 0 0 0 0 0 0 0 0 3.2249 -0.3868 -0.6529 C 0 0 2 0 0 0 0 0 0 0 0 0 3.8011 -1.7203 -0.3500 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5126 -0.0968 -2.1324 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9568 0.1549 -2.3964 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4561 1.2765 -1.5536 C 0 0 2 0 0 0 0 0 0 0 0 0 6.7932 1.5808 -1.7952 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4116 -0.7560 -0.2261 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1928 0.6162 0.5740 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9474 -0.2429 1.4928 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7906 2.1603 1.6665 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3724 2.8999 0.1343 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6465 3.0451 0.5850 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2157 1.6504 -0.0953 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9948 -0.3964 2.0627 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9650 1.3673 2.1936 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8822 0.0998 2.9092 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7331 1.5680 1.9301 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9609 -2.4985 0.7461 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2693 -1.9782 1.8209 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5839 -1.8438 2.3448 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4933 0.7751 -0.8548 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2198 -0.9491 -2.4241 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2802 -2.2691 -1.2537 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8943 -0.3466 -1.9530 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9262 -1.7390 0.7807 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3339 0.7490 -0.3558 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7223 -0.5675 2.3485 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8406 1.2201 1.9456 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5626 -0.2894 2.9935 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6765 1.4224 2.5450 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6352 2.1933 0.3297 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1196 2.1200 0.5393 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4479 1.3938 -0.9296 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3143 -2.8741 0.5128 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2729 -1.8260 1.9439 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7514 -2.5345 1.3086 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7903 -2.4210 -1.4831 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2510 -0.7593 -2.0810 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9979 -1.4667 -1.0231 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4525 -0.6331 -2.5709 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3782 1.1300 -1.2539 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2057 2.8670 -1.6415 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0019 1.2914 -1.9033 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3841 1.6450 -2.6397 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7755 -0.2761 1.0080 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1573 0.7863 0.6735 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7806 -0.5589 -0.5193 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1132 1.8900 1.3416 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2253 -2.8926 -0.8002 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3372 -1.7904 0.6179 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0834 -2.5636 -0.3591 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5768 -2.0160 -1.1186 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9160 0.7304 -2.5160 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2379 -1.0345 -2.6912 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6071 -0.7352 -2.3215 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0307 0.4858 -3.4644 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8732 2.1947 -1.8436 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3339 0.7519 -1.7961 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 1 7 9 1 0 9 10 1 0 10 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 6 13 18 1 0 18 19 1 1 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 23 25 1 0 23 26 1 0 22 27 1 0 11 28 1 0 9 29 1 0 29 30 1 1 29 31 1 0 31 32 1 0 32 33 1 0 33 34 1 0 33 2 1 0 29 4 1 0 16 7 1 0 27 18 1 0 16 12 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 6 5 42 1 0 5 43 1 0 6 44 1 0 6 45 1 0 8 46 1 0 8 47 1 0 8 48 1 0 9 49 1 6 10 50 1 0 10 51 1 0 11 52 1 6 12 53 1 1 13 54 1 6 14 55 1 0 14 56 1 0 15 57 1 0 15 58 1 0 17 59 1 0 17 60 1 0 17 61 1 0 19 62 1 0 19 63 1 0 19 64 1 0 20 65 1 0 20 66 1 0 21 67 1 0 21 68 1 0 22 69 1 6 24 70 1 0 24 71 1 0 24 72 1 0 25 73 1 0 25 74 1 0 25 75 1 0 26 76 1 0 28 77 1 0 30 78 1 0 30 79 1 0 30 80 1 0 31 81 1 0 31 82 1 0 32 83 1 0 32 84 1 0 33 85 1 6 34 86 1 0 M END

Standard InCHIKey	DOAJFZJEGHSYOI-BVGXOPESSA-N
Standard InCHI	InChI=1S/C30H52O4/c1-25(2)20-10-15-28(6)21(27(20,5)13-11-22(25)32)17-19(31)24-18(9-14-29(24,28)7)30(8)16-12-23(34-30)26(3,4)33/h18-24,31-33H,9-17H2,1-8H3/t18-,19+,20-,21+,22-,23-,24-,27-,28+,29+,30-/m0/s1
SMILES	CC1(C)[C@@H]2CC[C@]3(C)[C@H](C[C@H]([C@@H]4[C@H](CC[C@@]34C)[C@]3(C)CC[C@@H](C(C)(C)O)O3)O)[C@@]2(C)CC[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	476.39	Volume:	519.815 ? Van der Waals volume.
Dense:	0.916	LogP:	3.734 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.777 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.82 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	25.0
TPSA:	69.92 ? 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:	0.477	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.959	Fsp³:	1.0
MCE-18:	108.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.864	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:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.263	Promiscuous compounds:	0.368

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.493	MDCK Permeability:	-5.084
Pgp-inhibitor:	0.131	Pgp-substrate:	0.186
PAMPA:	0.874 ? 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%):	0.352	30% Bioavailability (F30%):	0.04
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.916	MRP1:	0.944
Plasma Protein Binding (PPB):	94.672%	Volume Distribution (VD):	-0.26
Fu:	5.465% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.989	BCRP inhibitor:	0.213
BSEP inhibitor:	0.859

ADMET: Metabolism

CYP1A2-inhibitor:	0.357	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	0.12	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.052	CYP2D6-substrate:	0.02
CYP3A4-inhibitor:	0.255	CYP3A4-substrate:	0.24
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.702
HLM stability:	0.615 ? 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):

11.189

Half-life (T1/2):

0.94

ADMET: Toxicity

hERG Blockers:	0.092	hERG Blockers (10um):	0.295
Human Hepatotoxicity (H-HT):	0.547	Drug-induced Liver Injury (DILI):	0.176
AMES Toxicity:	0.659	Rat Oral Acute Toxicity:	0.579
Maximum Recommended Daily Dose:	0.593	Skin Sensitization:	0.99
Carcinogencity:	0.855	Eye Corrosion:	0.089
Eye Irritation:	0.756	Respiratory Toxicity:	0.822
Drug-induced Neurotoxicity:	0.139	Ototoxicity:	0.564
Hematotoxicity:	0.512	Drug-induced Nephrotoxicity:	0.739
Genotoxicity:	0.752	RPMI-8226 Immunitoxicity:	0.088
A549 Cytotoxicity:	0.709	Hek293 Cytotoxicity:	0.667
BCF:	1.467 ? 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:	3.496 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.918 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.277 ? 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
NPO22221	Ibicella lutea	Species	Martyniaceae	Eukaryota	n.a.	El Volcan, Dpto. La Capital, Province of San Luis, Argentina	2001-MAR	PMID[14695802]
NPO22221	Ibicella lutea	Species	Martyniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22484	Aplidium cyaneum	Species	Polyclinidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23888	Chrysothamnus viscidiflorus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15834	Bonellia viridis	Species	Bonelliidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15834	Bonellia viridis	Species	Bonelliidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22484	Aplidium cyaneum	Species	Polyclinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23888	Chrysothamnus viscidiflorus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22221	Ibicella lutea	Species	Martyniaceae	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
Survival	5
IC50	4
MIC	6
FICI	2
Retention_time	1

Activity Type	# Activity
Cell line	3
Organism	8
Unchecked	4
Individual protein	1
Non-molecular	1
Tissue	1

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	Survival	=	104.0	%	PMID[30347326]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell line	A549	Homo sapiens	IC50	=	5.0	ug.mL-1	PMID[14695802]
NPT71	Cell line	HEK293	Homo sapiens	IC50	=	154.26	ug.mL-1	PMID[23994872]
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	47.64	ug.mL-1	PMID[23994872]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	5.0	ug.mL-1	PMID[14695802]
NPT2709	Organism	Bacillus subtilis subsp. subtilis str. 168	Bacillus subtilis subsp. subtilis str. 168	MIC	=	8.0	ug.mL-1	PMID[23994872]
NPT626	Tissue	Liver microsome	Homo sapiens	Retention_time	=	19.2	min	PMID[21139039]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	128.0	ug.mL-1	PMID[23994872]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	128.0	ug.mL-1	PMID[23994872]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	FICI	=	1.5	n.a.	PMID[23994872]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	FICI	=	0.14	n.a.	PMID[23994872]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	8.0	ug.mL-1	PMID[23994872]
NPT747	Organism	Acinetobacter baumannii	Acinetobacter baumannii	MIC	>	128.0	ug.mL-1	PMID[23994872]
NPT1101	Organism	Staphylococcus aureus subsp. aureus RN4220	Staphylococcus aureus subsp. aureus RN4220	MIC	=	8.0	ug.mL-1	PMID[23994872]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT28438	Unchecked	Unchecked	n.a.	Survival	=	86.45	%	PMID[36167009]
NPT28438	Unchecked	Unchecked	n.a.	Survival	n.a.	n.a.	n.a.	PMID[36167009]

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 NPC64081 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	23381
0.1-0.2	23282
0.2-0.3	2696
0.3-0.4	398
0.4-0.5	62
0.5-0.6	18
0.6-0.7	7
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
0.7857	Intermediate Similarity	NPC474574
0.7455	Intermediate Similarity	NPC91387
0.7455	Intermediate Similarity	NPC231680
0.7455	Intermediate Similarity	NPC270306
0.7143	Intermediate Similarity	NPC81074
0.7143	Intermediate Similarity	NPC477282
0.6949	Remote Similarity	NPC477285
0.6786	Remote Similarity	NPC282454
0.6613	Remote Similarity	NPC111582
0.6286	Remote Similarity	NPC82955
0.623	Remote Similarity	NPC133596
0.623	Remote Similarity	NPC11907
0.6094	Remote Similarity	NPC215968
0.5938	Remote Similarity	NPC155531
0.5806	Remote Similarity	NPC470071
0.5667	Remote Similarity	NPC301707
0.5645	Remote Similarity	NPC252182
0.5641	Remote Similarity	NPC229801
0.5593	Remote Similarity	NPC66407
0.5574	Remote Similarity	NPC1340
0.5432	Remote Similarity	NPC307167
0.5417	Remote Similarity	NPC66654
0.5323	Remote Similarity	NPC80530
0.5323	Remote Similarity	NPC3403
0.5323	Remote Similarity	NPC273410
0.5312	Remote Similarity	NPC157422
0.5312	Remote Similarity	NPC100586
0.5312	Remote Similarity	NPC109457
0.5301	Remote Similarity	NPC210759
0.5077	Remote Similarity	NPC245029
0.5077	Remote Similarity	NPC31302

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC64081 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7517
0.1-0.2	1593
0.2-0.3	37
0.3-0.4	2
0.4-0.5	1
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