NPASS Compound

Natural Product: NPC142731

Natural Product ID	NPC142731
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Ddd01025617
IUPAC Name	(2S,3S)-3,5,7-trihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one
Synonyms	(2S,3S)-3,4',5,7-Tetrahydroxyflavanone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1933859
PubChem CID	9838882
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0001632] Flavanones [CHEMONTID:0001362] Flavanonols

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 33 35 0 0 0 0 0 0 0 0999 V2000 -5.9485 0.9389 -0.4492 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6065 0.5897 -0.3101 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6785 1.4549 0.2310 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3489 1.0765 0.3558 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9008 -0.1663 -0.0506 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8162 -1.0311 -0.5890 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1488 -0.6480 -0.7125 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4717 -0.4740 0.1230 C 0 0 2 0 0 0 0 0 0 0 0 0 0.2548 0.6636 -0.3274 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6453 0.6718 -0.1738 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3797 1.7944 0.0674 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7545 1.7919 0.2178 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4231 2.9771 0.4607 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3924 0.5730 0.1133 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6778 -0.5889 -0.1313 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3069 -0.5417 -0.2749 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4883 -1.7203 -0.5333 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1220 -2.8168 -0.6893 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0017 -1.6773 -0.6155 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4915 -2.8567 -0.0494 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3368 -1.8143 -0.2344 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2359 1.8671 -0.7254 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0217 2.4381 0.5549 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6435 1.7777 0.7847 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4891 -2.0149 -0.9167 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8693 -1.3300 -1.1368 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2955 -0.6240 1.2076 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8357 2.7462 0.1440 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1581 3.6558 1.1558 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4474 0.5170 0.2209 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2737 -1.6145 -1.7020 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6423 -3.5435 -0.7453 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6581 -2.0715 -1.1480 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 2 0 5 6 1 0 6 7 2 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 17 19 1 0 19 20 1 0 15 21 1 0 7 2 1 0 19 8 1 0 16 10 1 0 1 22 1 0 3 23 1 0 4 24 1 0 6 25 1 0 7 26 1 0 8 27 1 1 11 28 1 0 13 29 1 0 14 30 1 0 19 31 1 6 20 32 1 0 21 33 1 0 M END

Standard InCHIKey	PADQINQHPQKXNL-CABCVRRESA-N
Standard InCHI	InChI=1S/C15H12O6/c16-8-3-1-7(2-4-8)15-14(20)13(19)12-10(18)5-9(17)6-11(12)21-15/h1-6,14-18,20H/t14-,15+/m1/s1
SMILES	Oc1ccc(cc1)[C@@H]1Oc2cc(O)cc(c2C(=O)[C@H]1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	288.06	Volume:	276.613 ? Van der Waals volume.
Dense:	1.041	LogP:	1.163 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.422 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.614 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	107.22 ? 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:	0.633	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.206	Fsp³:	0.133
MCE-18:	58.235 ? 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:	0.486	Fluc inhibitor:	0.544 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.105 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.195 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.553	Promiscuous compounds:	0.279

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.26	MDCK Permeability:	-4.902
Pgp-inhibitor:	0.314	Pgp-substrate:	0.4
PAMPA:	0.415 ? 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):	0.002
20% Bioavailability (F20%):	0.03	30% Bioavailability (F30%):	0.958
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.703
Plasma Protein Binding (PPB):	94.685%	Volume Distribution (VD):	-0.068
Fu:	7.531% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.935
BSEP inhibitor:	0.59

ADMET: Metabolism

CYP1A2-inhibitor:	0.564	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.022
CYP2C9-inhibitor:	0.482	CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.956
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.458
HLM stability:	0.57 ? 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):

8.534

Half-life (T1/2):

1.634

ADMET: Toxicity

hERG Blockers:	0.099	hERG Blockers (10um):	0.493
Human Hepatotoxicity (H-HT):	0.914	Drug-induced Liver Injury (DILI):	0.518
AMES Toxicity:	0.672	Rat Oral Acute Toxicity:	0.648
Maximum Recommended Daily Dose:	0.607	Skin Sensitization:	0.995
Carcinogencity:	0.434	Eye Corrosion:	0.006
Eye Irritation:	0.993	Respiratory Toxicity:	0.486
Drug-induced Neurotoxicity:	0.602	Ototoxicity:	0.273
Hematotoxicity:	0.196	Drug-induced Nephrotoxicity:	0.793
Genotoxicity:	0.983	RPMI-8226 Immunitoxicity:	0.163
A549 Cytotoxicity:	0.837	Hek293 Cytotoxicity:	0.852
BCF:	1.23 ? 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:	3.53 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.404 ? 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
NPO19123	Polygonatum zanlanscianense	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15620239]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	stems	n.a.	n.a.	PMID[16252910]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	anomalous fruits	n.a.	n.a.	PMID[25442304]
NPO7631	Gleditsia japonica	Species	Fabaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[7494144]
NPO3010	Nidorella hottentotica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19123	Polygonatum zanlanscianense	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26259	Streptomyces rimofaciens	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7631	Gleditsia japonica	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19123	Polygonatum zanlanscianense	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19123	Polygonatum zanlanscianense	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7631	Gleditsia japonica	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO3010	Nidorella hottentotica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5452	Curcuma parviflora	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7132	Smilax glabra	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20608	Gleditsia sinensis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16448	Corydalis pseudoadunca	Species	Papaveraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7631	Gleditsia japonica	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19123	Polygonatum zanlanscianense	Species	Asparagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25611	Smilax china	Species	Smilacaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26259	Streptomyces rimofaciens	Species	Streptomycetaceae	Bacteria	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
Inhibition	7
Percent Effect	13
IC50	2

Activity Type	# Activity
Individual protein	1
Cell line	2
Single protein	9
Organism	8
Others	1
Protein complex	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT21964	Single protein	Histidine--tRNA ligase	Trypanosoma cruzi (strain CL Brener)	Percent Effect	=	4.95	%	DOI[10.6019/CHEMBL3988442]
NPT21965	Single protein	Tryptophan--tRNA ligase	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Percent Effect	=	-0.8283	%	DOI[10.6019/CHEMBL3988442]
NPT21962	Single protein	Methionyl-tRNA synthetase, putative	Leishmania donovani (strain BPK282A1)	Inhibition	=	4.945	%	DOI[10.6019/CHEMBL3988442]
NPT21966	Single protein	Polyketide synthase Pks13	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Percent Effect	=	3.919	%	DOI[10.6019/CHEMBL3988442]
NPT21968	Single protein	Histidine--tRNA ligase	Leishmania infantum	Percent Effect	=	2.778	%	DOI[10.6019/CHEMBL3988442]
NPT21963	Single protein	Coenzyme A biosynthesis bifunctional protein CoaBC	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Percent Effect	=	-3.175	%	DOI[10.6019/CHEMBL3988442]
NPT21963	Single protein	Coenzyme A biosynthesis bifunctional protein CoaBC	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Percent Effect	=	26.41	%	DOI[10.6019/CHEMBL3988442]
NPT3565	Individual protein	Lysine--tRNA ligase	Plasmodium falciparum (isolate 3D7)	Percent Effect	=	1.676	%	DOI[10.6019/CHEMBL3988442]
NPT21963	Single protein	Coenzyme A biosynthesis bifunctional protein CoaBC	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	IC50	>	30199.52	nM	DOI[10.6019/CHEMBL3988442]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT113	Cell line	RAW264.7	Mus musculus	Inhibition	<	10.0	%	PMID[26481151]
NPT65	Cell line	HepG2	Homo sapiens	INHIBITION	=	-0.639	%	PMID[32078764]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	INHIBITION	=	1.17	%	PMID[32078764]
NPT21970	Organism	Wolbachia pipientis	Wolbachia pipientis	Percent Effect	=	0.6664	%	DOI[10.6019/CHEMBL3988442]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	Percent Effect	=	-202.53	%	DOI[10.6019/CHEMBL3988442]
NPT633	Organism	Leishmania donovani	Leishmania donovani	Percent Effect	=	5.908	%	DOI[10.6019/CHEMBL3988442]
NPT21967	Protein complex	ClpP1P2	Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)	Percent Effect	=	-2.15	%	DOI[10.6019/CHEMBL3988442]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	Percent Effect	=	53.66	%	DOI[10.6019/CHEMBL3988442]
NPT474	Organism	Plasmodium berghei	Plasmodium berghei	INHIBITION	=	19.98	%	PMID[32078764]
NPT474	Organism	Plasmodium berghei	Plasmodium berghei	INHIBITION	=	70.8	%	PMID[32078764]
NPT1018	Organism	Trypanosoma brucei	Trypanosoma brucei	Percent Effect	=	-10.78	%	DOI[10.6019/CHEMBL3988442]
NPT2	Others	Unspecified	n.a.	Inhibition	=	-7.811	%	DOI[10.6019/CHEMBL3507680]

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 NPC142731 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	24968
0.1-0.2	20370
0.2-0.3	3690
0.3-0.4	595
0.4-0.5	140
0.5-0.6	51
0.6-0.7	11
0.7-0.8	0
0.8-0.85	7
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC62290
1.0	High Similarity	NPC326506
0.8261	Intermediate Similarity	NPC4152
0.8125	Intermediate Similarity	NPC36835
0.8125	Intermediate Similarity	NPC246162
0.8125	Intermediate Similarity	NPC9743
0.8125	Intermediate Similarity	NPC260491
0.8125	Intermediate Similarity	NPC61506
0.8125	Intermediate Similarity	NPC240476
0.7917	Intermediate Similarity	NPC44721
0.7917	Intermediate Similarity	NPC211466
0.7917	Intermediate Similarity	NPC605332
0.7872	Intermediate Similarity	NPC279417
0.7872	Intermediate Similarity	NPC49130
0.766	Intermediate Similarity	NPC21835
0.75	Intermediate Similarity	NPC326037
0.75	Intermediate Similarity	NPC13858
0.7347	Intermediate Similarity	NPC19721
0.7234	Intermediate Similarity	NPC1940
0.72	Intermediate Similarity	NPC176869
0.72	Intermediate Similarity	NPC306607
0.72	Intermediate Similarity	NPC3779
0.7143	Intermediate Similarity	NPC208176
0.7115	Intermediate Similarity	NPC320825
0.7059	Intermediate Similarity	NPC250922
0.7	Intermediate Similarity	NPC201837
0.6863	Remote Similarity	NPC606962
0.6667	Remote Similarity	NPC63438
0.6545	Remote Similarity	NPC20907
0.6275	Remote Similarity	NPC148011
0.6182	Remote Similarity	NPC244250
0.6078	Remote Similarity	NPC207179
0.6078	Remote Similarity	NPC167571
0.6078	Remote Similarity	NPC278552
0.6038	Remote Similarity	NPC246328
0.6038	Remote Similarity	NPC27532
0.6	Remote Similarity	NPC186847
0.5962	Remote Similarity	NPC201227
0.5962	Remote Similarity	NPC32441
0.5962	Remote Similarity	NPC258474
0.5962	Remote Similarity	NPC79943
0.5821	Remote Similarity	NPC36916
0.5821	Remote Similarity	NPC36
0.5821	Remote Similarity	NPC7154
0.5821	Remote Similarity	NPC125039
0.5821	Remote Similarity	NPC7688
0.5763	Remote Similarity	NPC262038
0.5763	Remote Similarity	NPC319910
0.5758	Remote Similarity	NPC606364
0.5741	Remote Similarity	NPC325028
0.5741	Remote Similarity	NPC256346
0.5741	Remote Similarity	NPC122828
0.5741	Remote Similarity	NPC606550
0.5735	Remote Similarity	NPC138688
0.5735	Remote Similarity	NPC72787
0.5735	Remote Similarity	NPC217795
0.5735	Remote Similarity	NPC58223
0.5714	Remote Similarity	NPC611035
0.5652	Remote Similarity	NPC279209
0.5652	Remote Similarity	NPC102277
0.5652	Remote Similarity	NPC479117
0.5625	Remote Similarity	NPC153342
0.5614	Remote Similarity	NPC52530
0.5574	Remote Similarity	NPC217706
0.5571	Remote Similarity	NPC75827
0.5556	Remote Similarity	NPC610035
0.5536	Remote Similarity	NPC609065
0.5373	Remote Similarity	NPC262039
0.537	Remote Similarity	NPC476182
0.5357	Remote Similarity	NPC263449
0.5345	Remote Similarity	NPC471744
0.5303	Remote Similarity	NPC160156
0.5303	Remote Similarity	NPC92565
0.5254	Remote Similarity	NPC123544
0.5254	Remote Similarity	NPC484335
0.5224	Remote Similarity	NPC603037
0.5091	Remote Similarity	NPC295261
0.5091	Remote Similarity	NPC296490
0.5088	Remote Similarity	NPC321011
0.5088	Remote Similarity	NPC294852
0.5088	Remote Similarity	NPC481903
0.5088	Remote Similarity	NPC188679
0.5075	Remote Similarity	NPC270578
0.5075	Remote Similarity	NPC250963
0.5075	Remote Similarity	NPC274256
0.5075	Remote Similarity	NPC109582
0.5075	Remote Similarity	NPC291220
0.5075	Remote Similarity	NPC52382

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC142731 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4867
0.1-0.2	4156
0.2-0.3	115
0.3-0.4	3
0.4-0.5	3
0.5-0.6	4
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
0.5962	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5821	Remote Similarity	NPD6166	Phase 2
0.5821	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5821	Remote Similarity	NPD6168	Clinical (unspecified phase)

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