NPASS Compound

Natural Product: NPC473330

Natural Product ID	NPC473330
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Elephantopin
IUPAC Name	n.a.
Synonyms	Elephantopin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL400927
PubChem CID	442206
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001986] Tricarboxylic acids and derivatives

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 46 49 0 0 0 0 0 0 0 0999 V2000 4.9002 -0.4819 -0.6730 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3767 -0.4986 0.5277 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2251 -0.8065 1.6939 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9701 -0.2152 0.7019 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4628 -0.2300 1.8527 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1178 0.0806 -0.3472 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7288 0.3528 -0.1107 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3993 1.7543 -0.5432 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9859 2.1559 -0.2046 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9516 1.9967 -1.0680 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2637 2.2993 -0.4816 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1277 1.0796 -0.2290 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3082 -0.0745 0.2992 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.2043 -0.1626 1.7947 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5112 -0.7853 -0.5601 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2024 -1.2206 0.0112 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1043 -0.6838 -0.8425 C 0 0 2 0 0 0 0 0 0 0 0 0 0.7288 -1.8729 -1.2011 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7134 -2.0012 -2.0624 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2186 -2.9482 -0.3650 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8805 -4.0045 -0.0817 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0645 -2.6269 0.0492 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7139 -1.4013 -0.2285 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9153 2.9416 0.7291 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5750 2.7727 0.9907 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9098 3.0617 2.0211 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9480 -0.6942 -0.7939 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3134 -0.2623 -1.5394 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9594 0.0045 1.8978 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7850 -1.7529 1.4406 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5739 -1.0417 2.5481 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5677 0.2711 0.9717 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5060 1.7980 -1.6507 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0613 2.5074 -0.0523 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8306 1.6865 -2.0949 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8440 3.0274 -1.0841 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9219 1.3912 0.4818 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6386 0.8161 -1.1778 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3692 -1.1844 2.2092 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2695 0.2584 2.2134 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0339 0.4551 2.2499 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4725 -0.5800 -1.6683 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0273 -0.8390 1.0429 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4745 -0.2382 -1.7904 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0683 -1.1707 -2.6732 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2145 -2.9334 -2.2032 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 2 0 4 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 1 13 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 2 0 20 22 1 0 15 23 1 0 11 24 1 0 24 25 1 0 25 26 2 0 17 7 1 0 25 9 1 0 23 13 1 0 22 16 1 0 1 27 1 0 1 28 1 0 3 29 1 0 3 30 1 0 3 31 1 0 7 32 1 1 8 33 1 0 8 34 1 0 10 35 1 0 11 36 1 6 12 37 1 0 12 38 1 0 14 39 1 0 14 40 1 0 14 41 1 0 15 42 1 6 16 43 1 1 17 44 1 6 19 45 1 0 19 46 1 0 M END

Standard InCHIKey	WIQOUTANBFOBPB-KIVXNUBRSA-N
Standard InCHI	InChI=1S/C19H20O7/c1-8(2)16(20)24-12-6-10-5-11(23-18(10)22)7-19(4)15(26-19)14-13(12)9(3)17(21)25-14/h5,11-15H,1,3,6-7H2,2,4H3/t11-,12-,13+,14-,15+,19+/m0/s1
SMILES	C=C(C)C(=O)O[C@H]1CC2=C[C@@H](C[C@]3(C)[C@@H]([C@@H]4[C@@H]1C(=C)C(=O)O4)O3)OC2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	360.12	Volume:	348.667 ? Van der Waals volume.
Dense:	1.033	LogP:	1.615 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.907 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.522 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	91.43 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.318	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.181	Fsp³:	0.526
MCE-18:	66.345 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.758	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.038 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.414	Promiscuous compounds:	0.441

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.815	MDCK Permeability:	-4.672
Pgp-inhibitor:	0.474	Pgp-substrate:	0.661
PAMPA:	0.814 ? 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):	0.079
20% Bioavailability (F20%):	0.99	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.321	MRP1:	0.678
Plasma Protein Binding (PPB):	50.171%	Volume Distribution (VD):	0.17
Fu:	51.502% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.079
BSEP inhibitor:	0.983

ADMET: Metabolism

CYP1A2-inhibitor:	0.041	CYP1A2-substrate:	0.069
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.127
CYP2C9-inhibitor:	0.058	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.141
CYP3A4-inhibitor:	0.147	CYP3A4-substrate:	0.136
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.617
HLM stability:	0.705 ? 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):

5.988

Half-life (T1/2):

1.692

ADMET: Toxicity

hERG Blockers:	0.03	hERG Blockers (10um):	0.221
Human Hepatotoxicity (H-HT):	0.764	Drug-induced Liver Injury (DILI):	0.988
AMES Toxicity:	0.819	Rat Oral Acute Toxicity:	0.268
Maximum Recommended Daily Dose:	0.575	Skin Sensitization:	0.999
Carcinogencity:	0.825	Eye Corrosion:	0.072
Eye Irritation:	0.759	Respiratory Toxicity:	0.117
Drug-induced Neurotoxicity:	0.773	Ototoxicity:	0.682
Hematotoxicity:	0.438	Drug-induced Nephrotoxicity:	0.941
Genotoxicity:	0.823	RPMI-8226 Immunitoxicity:	0.123
A549 Cytotoxicity:	0.216	Hek293 Cytotoxicity:	0.214
BCF:	1.051 ? 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:	3.663 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.415 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.881 ? 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
NPO33469	Asteraceae	Family	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18329753]
NPO2053	Elephantopus nudatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[3839258]
NPO33469	Asteraceae	Family	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2053	Elephantopus nudatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2053	Elephantopus nudatus	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
pED50	1
ED50	4
T/C	2
GI50	58

Activity Type	# Activity
Cell line	65

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
NPT91	Cell line	KB	Homo sapiens	pED50	=	5.6	n.a.	PMID[17336532]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.94	ug ml-1	PMID[15730238]
NPT91	Cell line	KB	Homo sapiens	ED50	=	0.32	ug	PMID[24239390]
NPT168	Cell line	P388	Mus musculus	T/C	=	160.0	%	PMID[3839258]
NPT168	Cell line	P388	Mus musculus	T/C	=	171.0	%	PMID[3839258]
NPT91	Cell line	KB	Homo sapiens	ED50	=	2.51	umol/L	PMID[19654408]
NPT368	Cell line	SN12C	Homo sapiens	GI50	n.a.	4027.17	nM	PMID[17844994]
NPT370	Cell line	NCI-H23	Homo sapiens	GI50	n.a.	1870.68	nM	PMID[9514015]
NPT371	Cell line	UO-31	Homo sapiens	GI50	n.a.	6067.36	nM	PMID[9644083]
NPT116	Cell line	HL-60	Homo sapiens	GI50	n.a.	486.41	nM	PMID[16872133]
NPT372	Cell line	HOP-92	Homo sapiens	GI50	n.a.	1129.8	nM	DOI[10.6019/CHEMBL1201861]
NPT374	Cell line	SF-539	Homo sapiens	GI50	n.a.	3572.73	nM	PMID[21036050]
NPT373	Cell line	SK-MEL-5	Homo sapiens	GI50	n.a.	4285.49	nM	PMID[18077363]
NPT375	Cell line	Malme-3M	Homo sapiens	GI50	n.a.	2118.36	nM	PubChem BioAssay data set
NPT376	Cell line	A498	Homo sapiens	GI50	n.a.	5128.61	nM	PubChem BioAssay data set
NPT111	Cell line	K562	Homo sapiens	GI50	n.a.	1006.93	nM	PubChem BioAssay data set
NPT377	Cell line	OVCAR-3	Homo sapiens	GI50	n.a.	1202.26	nM	PMID[11277765]
NPT112	Cell line	MOLT-4	Homo sapiens	GI50	n.a.	412.1	nM	PubChem BioAssay data set
NPT379	Cell line	HOP-62	Homo sapiens	GI50	n.a.	52480.75	nM	DrugMatrix in vivo data: Biochemistry
NPT380	Cell line	U-251	Homo sapiens	GI50	n.a.	6486.34	nM	DOI[10.6019/CHEMBL1201861]
NPT378	Cell line	NCI/ADR-RES	Homo sapiens	GI50	n.a.	1140.25	nM	DrugMatrix in vivo data: Biochemistry
NPT382	Cell line	OVCAR-5	Homo sapiens	GI50	n.a.	6546.36	nM	PMID[24268596]
NPT381	Cell line	OVCAR-8	Homo sapiens	GI50	n.a.	504.66	nM	PMID[12517096]
NPT383	Cell line	SNB-19	Homo sapiens	GI50	n.a.	13335.21	nM	PMID[16933872]
NPT572	Cell line	DMS-273	Homo sapiens	GI50	n.a.	2786.12	nM	PMID[24571273]
NPT323	Cell line	SW-620	Homo sapiens	GI50	n.a.	695.02	nM	PMID[21658941]
NPT573	Cell line	M19-MEL	Homo sapiens	GI50	n.a.	2494.59	nM	PMID[27161176]
NPT455	Cell line	NCI-H522	Homo sapiens	GI50	n.a.	592.93	nM	PMID[22537362]
NPT386	Cell line	KM12	Homo sapiens	GI50	n.a.	3311.31	nM	PMID[24012119]
NPT574	Cell line	XF498	Homo sapiens	GI50	n.a.	1909.85	nM	DrugMatrix in vitro pharmacology data
NPT388	Cell line	NCI-H322M	Homo sapiens	GI50	n.a.	1909.85	nM	PMID[19721074]
NPT389	Cell line	RPMI-8226	Homo sapiens	GI50	n.a.	345.94	nM	PMID[22364566]
NPT456	Cell line	OVCAR-4	Homo sapiens	GI50	n.a.	2606.15	nM	PubChem BioAssay data set
NPT390	Cell line	LOX IMVI	Homo sapiens	GI50	n.a.	310.46	nM	PMID[16499318]
NPT168	Cell line	P388	Mus musculus	GI50	n.a.	123.88	nM	PubChem BioAssay data set
NPT147	Cell line	SK-MEL-2	Homo sapiens	GI50	n.a.	4335.11	nM	PMID[18426901]
NPT575	Cell line	KM-20L2	Homo sapiens	GI50	n.a.	4688.13	nM	PMID[22440015]
NPT81	Cell line	A549	Homo sapiens	GI50	n.a.	7328.25	nM	DOI[10.6019/CHEMBL1201861]
NPT391	Cell line	HCC 2998	Homo sapiens	GI50	n.a.	5105.05	nM	PMID[19902967]
NPT392	Cell line	SNB-75	Homo sapiens	GI50	n.a.	7979.95	nM	PMID[19097894]
NPT148	Cell line	HCT-15	Homo sapiens	GI50	n.a.	926.83	nM	PMID[23398362]
NPT393	Cell line	HCT-116	Homo sapiens	GI50	n.a.	1158.78	nM	PMID[7783146]
NPT395	Cell line	SF-268	Homo sapiens	GI50	n.a.	818.46	nM	PubChem BioAssay data set
NPT83	Cell line	MCF7	Homo sapiens	GI50	n.a.	1142.88	nM	PMID[19654408]
NPT394	Cell line	EKVX	Homo sapiens	GI50	n.a.	2084.49	nM	PMID[18591277]
NPT576	Cell line	DMS-114	Homo sapiens	GI50	n.a.	4466.84	nM	PMID[22503207]
NPT146	Cell line	SK-OV-3	Homo sapiens	GI50	n.a.	11534.53	nM	PMID[19581457]
NPT397	Cell line	NCI-H460	Homo sapiens	GI50	n.a.	4864.07	nM	PubChem BioAssay data set
NPT398	Cell line	UACC-62	Homo sapiens	GI50	n.a.	3499.45	nM	PMID[2045816]
NPT552	Cell line	P388/ADR	Mus musculus	GI50	n.a.	165.58	nM	PMID[22939698]
NPT308	Cell line	CAKI-1	Homo sapiens	GI50	n.a.	1857.8	nM	PMID[3302260]
NPT458	Cell line	IGROV-1	Homo sapiens	GI50	n.a.	4645.15	nM	PubChem BioAssay data set
NPT399	Cell line	SF-295	Homo sapiens	GI50	n.a.	5571.86	nM	PMID[24195447]
NPT403	Cell line	UACC-257	Homo sapiens	GI50	n.a.	1849.27	nM	PMID[26287401]
NPT578	Cell line	SNB-78	Homo sapiens	GI50	n.a.	2094.11	nM	PMID[17844995]
NPT579	Cell line	DLD-1	Homo sapiens	GI50	n.a.	897.43	nM	DOI[10.1007/s00044-012-0230-8]
NPT404	Cell line	CCRF-CEM	Homo sapiens	GI50	n.a.	516.42	nM	PMID[20805391]
NPT405	Cell line	NCI-H226	Homo sapiens	GI50	n.a.	10232.93	nM	PMID[21924800]
NPT170	Cell line	SK-MEL-28	Homo sapiens	GI50	n.a.	1706.08	nM	PMID[2157014]
NPT139	Cell line	HT-29	Homo sapiens	GI50	n.a.	2477.42	nM	PMID[18458131]
NPT407	Cell line	COLO 205	Homo sapiens	GI50	n.a.	885.12	nM	PMID[20541427]
NPT406	Cell line	RXF 393	Homo sapiens	GI50	n.a.	368.98	nM	PMID[17190458]
NPT732	Cell line	HOP-18	Homo sapiens	GI50	n.a.	4325.14	nM	PMID[23398362]
NPT738	Cell line	SN12K1	Homo sapiens	GI50	n.a.	4731.51	nM	PMID[21517059]
NPT91	Cell line	KB	Homo sapiens	ED50	=	1.0	ug ml-1	PMID[20476748]

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 NPC473330 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	26243
0.1-0.2	21752
0.2-0.3	1533
0.3-0.4	264
0.4-0.5	48
0.5-0.6	11
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8269	Intermediate Similarity	NPC473316
0.6724	Remote Similarity	NPC279561
0.5862	Remote Similarity	NPC473326
0.5862	Remote Similarity	NPC481994
0.5818	Remote Similarity	NPC610417
0.5763	Remote Similarity	NPC481908
0.5763	Remote Similarity	NPC481993
0.5345	Remote Similarity	NPC151770
0.5263	Remote Similarity	NPC609300
0.5238	Remote Similarity	NPC483718
0.5172	Remote Similarity	NPC600792
0.5172	Remote Similarity	NPC610427
0.5085	Remote Similarity	NPC609663

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC473330 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7439
0.1-0.2	1699
0.2-0.3	11
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