NPASS Compound

Natural Product: NPC196277

Natural Product ID	NPC196277
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1,3,5,6-Tetrahydroxyxanthen-9-One
IUPAC Name	1,3,5,6-tetrahydroxyxanthen-9-one
Synonyms	1,3,5,6-Tetrahydroxyxanthone; 1,3,5,6-Tetrahydroxyxantone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448040
PubChem CID	5479774
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000123] Benzopyrans [CHEMONTID:0003410] 1-benzopyrans [CHEMONTID:0002817] Dibenzopyrans [CHEMONTID:0000200] Xanthenes [CHEMONTID:0000204] Xanthones

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 27 29 0 0 0 0 0 0 0 0999 V2000 -4.6614 1.5620 0.5883 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5138 0.8199 0.3751 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6108 -0.5129 0.1201 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4829 -1.2595 -0.0928 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5672 -2.6246 -0.3549 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2146 -0.6967 -0.0578 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1357 0.6549 0.2021 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2914 1.4147 0.4192 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0486 1.2126 0.2411 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1548 0.5392 0.0438 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1289 -0.8116 -0.2190 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0799 -1.4652 -0.2753 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2098 -2.6919 -0.5077 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2973 -1.5246 -0.4277 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5356 -0.9002 -0.3789 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5887 0.4482 -0.1181 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4147 1.1375 0.0863 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4647 2.4951 0.3490 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8008 1.1515 -0.0523 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9375 1.9644 1.4647 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5791 -0.9935 0.0834 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3916 -2.9337 -1.3190 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1331 2.4547 0.6133 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2563 -2.5817 -0.6322 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4600 -1.4278 -0.5368 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4631 3.1317 -0.4578 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1954 1.4374 0.8442 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 4 6 2 0 6 7 1 0 7 8 2 0 7 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 11 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 16 19 1 0 8 2 1 0 17 10 1 0 12 6 1 0 1 20 1 0 3 21 1 0 5 22 1 0 8 23 1 0 14 24 1 0 15 25 1 0 18 26 1 0 19 27 1 0 M END

Standard InCHIKey	CCEBJWKUMKKCDF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H8O6/c14-5-3-8(16)10-9(4-5)19-13-6(11(10)17)1-2-7(15)12(13)18/h1-4,14-16,18H
SMILES	Oc1cc(O)c2c(c1)oc1c(c2=O)ccc(c1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	260.03	Volume:	242.021 ? Van der Waals volume.
Dense:	1.074	LogP:	1.438 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.7 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.995 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	17.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.362	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.511	Fsp³:	0.0
MCE-18:	18.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.829	Fluc inhibitor:	0.534 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.939 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.204 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.753	Promiscuous compounds:	0.874

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.763	MDCK Permeability:	-4.887
Pgp-inhibitor:	0.02	Pgp-substrate:	0.435
PAMPA:	0.451 ? 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):	0.057
20% Bioavailability (F20%):	0.642	30% Bioavailability (F30%):	0.945
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.03	MRP1:	0.73
Plasma Protein Binding (PPB):	96.101%	Volume Distribution (VD):	-0.723
Fu:	3.659% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.728
OATP1B3 inhibitor:	0.933	BCRP inhibitor:	0.956
BSEP inhibitor:	0.295

ADMET: Metabolism

CYP1A2-inhibitor:	0.419	CYP1A2-substrate:	0.175
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.332
CYP2C9-inhibitor:	0.554	CYP2C9-substrate:	0.425
CYP2D6-inhibitor:	0.93	CYP2D6-substrate:	0.988
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.019
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.937 ? 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):

7.209

Half-life (T1/2):

1.361

ADMET: Toxicity

hERG Blockers:	0.039	hERG Blockers (10um):	0.446
Human Hepatotoxicity (H-HT):	0.393	Drug-induced Liver Injury (DILI):	0.872
AMES Toxicity:	0.757	Rat Oral Acute Toxicity:	0.533
Maximum Recommended Daily Dose:	0.749	Skin Sensitization:	0.841
Carcinogencity:	0.699	Eye Corrosion:	0.397
Eye Irritation:	0.998	Respiratory Toxicity:	0.688
Drug-induced Neurotoxicity:	0.005	Ototoxicity:	0.104
Hematotoxicity:	0.045	Drug-induced Nephrotoxicity:	0.012
Genotoxicity:	0.976	RPMI-8226 Immunitoxicity:	0.028
A549 Cytotoxicity:	0.404	Hek293 Cytotoxicity:	0.525
BCF:	1.126 ? 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:	3.688 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.461 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.999 ? 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
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1007/s11240-015-0798-z]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.fitote.2006.01.011]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.plaphy.2005.07.013]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1078/0176-1617-00195]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1155/2014/609649]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10757735]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14735439]
NPO25854	Tripterospermum lanceolatum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[1517742]
NPO11713	Hypericum scabrum	Species	Hypericaceae	Eukaryota	n.a.	Uzbekistan	n.a.	PMID[15568778]
NPO11713	Hypericum scabrum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15568778]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	callus	n.a.	PMID[15715262]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18220354]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19191562]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21682262]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	whole plants	Zhejiang Province, China	2008-AUG	PMID[21682262]
NPO11713	Hypericum scabrum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27280968]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28445039]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	Roots	n.a.	n.a.	PMID[30024167]
NPO40853	Garcinia tetrandra	Species	Clusiaceae	Eukaryota	Stem Bark	n.a.	n.a.	PMID[30978023]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32560389]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36336219]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38217369]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7189773]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25854	Tripterospermum lanceolatum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO10519	Angylocalyx vermeulenii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15613	Clerodendrum uncinatum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13912	Delphinium gracile	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4475	Erythrina costaricensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15236	Leucetta avocado	Species	Leucettidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26692	Lophium arboricola	Species	Mytilinidiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11713	Hypericum scabrum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7544	Squalus wakiyae	Species	Squalidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO1645	Sticta pulmonaria	Species	Lobariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO40853	Garcinia tetrandra	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO9680	Ajuga ciliata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10519	Angylocalyx vermeulenii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15613	Clerodendrum uncinatum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4475	Erythrina costaricensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4391	Hypericum perforatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11713	Hypericum scabrum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1645	Sticta pulmonaria	Species	Lobariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25854	Tripterospermum lanceolatum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7544	Squalus wakiyae	Species	Squalidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12096	Psorospermum febrifugum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15236	Leucetta avocado	Species	Leucettidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13912	Delphinium gracile	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26692	Lophium arboricola	Species	Mytilinidiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9680	Ajuga ciliata	Species	Lamiaceae	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	11
Inhibition	4
Ki	1

Activity Type	# Activity
Individual protein	5
Cell line	9
Protein complex	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	IC50	=	69200.0	nM	PMID[1517742]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Inhibition	=	56.4	%	PMID[1517742]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Inhibition	=	67.66	%	PMID[1517742]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Inhibition	=	75.32	%	PMID[1517742]
NPT1166	Individual protein	Angiotensin-converting enzyme	Homo sapiens	Ki	=	34200.0	nM	PMID[1517742]
NPT2890	Protein complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	=	60000	nM	Patent: US9114126 B2
NPT2890	Protein complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	=	60000.0	nM	Patent: US9114126 B2

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	=	10000.0	ug.mL-1	PMID[15568778]
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	9300.0	ug.mL-1	PMID[15568778]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	18600.0	nM	PMID[30684866]
NPT91	Cell line	KB	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT65	Cell line	HepG2	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT139	Cell line	HT-29	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	=	78.9	%	PMID[31255927]
NPT20987	Cell line	HeLa S3	Homo sapiens	IC50	>	10000.0	nM	PMID[30978023]

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 NPC196277 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	36971
0.1-0.2	10919
0.2-0.3	1538
0.3-0.4	351
0.4-0.5	59
0.5-0.6	9
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
0.7021	Intermediate Similarity	NPC272721
0.6809	Remote Similarity	NPC601929
0.6383	Remote Similarity	NPC194856
0.625	Remote Similarity	NPC169479
0.619	Remote Similarity	NPC77378
0.617	Remote Similarity	NPC248102
0.6078	Remote Similarity	NPC151473
0.6042	Remote Similarity	NPC61620
0.5918	Remote Similarity	NPC239495
0.5714	Remote Similarity	NPC600210
0.5614	Remote Similarity	NPC115853
0.56	Remote Similarity	NPC276930
0.537	Remote Similarity	NPC179183
0.5306	Remote Similarity	NPC43669
0.5094	Remote Similarity	NPC202157
0.5091	Remote Similarity	NPC101996
0.5082	Remote Similarity	NPC608857

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC196277 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7365
0.1-0.2	1753
0.2-0.3	27
0.3-0.4	3
0.4-0.5	2
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