NPASS Compound

Natural Product: NPC86847

Natural Product ID	NPC86847
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2E)-2-[(3,4-Dihydroxyphenyl)Methylidene]-6-Hydroxy-1-Benzofuran-3-One
IUPAC Name	(2E)-2-[(3,4-dihydroxyphenyl)methylidene]-6-hydroxy-1-benzofuran-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL513487
PubChem CID	5321560
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0001631] Aurone flavonoids

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 30 32 0 0 0 0 0 0 0 0999 V2000 -2.1718 0.1004 -1.3392 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2983 0.8971 -1.3978 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3114 0.7716 -0.4778 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1637 -0.1837 0.5134 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0351 -0.9726 0.5633 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9977 -0.8608 -0.3594 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8343 -1.6951 -0.2252 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3835 -1.1977 -0.1157 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7627 0.2054 -0.1019 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0499 1.2190 -0.1805 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2318 0.3083 0.0320 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0991 1.3756 0.0951 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4556 1.1862 0.2234 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8984 -0.1155 0.2851 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0299 -1.1903 0.2221 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6650 -1.0007 0.0928 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5932 -1.8775 0.0075 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2708 -0.3236 0.4151 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1886 -0.3087 1.4407 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4214 1.5938 -0.5785 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4145 0.2135 -2.0989 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4130 1.6444 -2.1733 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9279 -1.7196 1.3436 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9574 -2.7929 -0.2128 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7543 2.3934 0.0480 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1846 1.9958 0.2777 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4124 -2.2106 0.2733 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8070 -0.0160 1.2079 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9934 0.0560 2.3673 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4698 2.5047 -0.1473 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 14 18 1 0 4 19 1 0 3 20 1 0 6 1 1 0 17 8 1 0 16 11 1 0 1 21 1 0 2 22 1 0 5 23 1 0 7 24 1 0 12 25 1 0 13 26 1 0 15 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	RGNXWPVNPFAADO-MKMNVTDBSA-N
Standard InCHI	InChI=1S/C15H10O5/c16-9-2-3-10-13(7-9)20-14(15(10)19)6-8-1-4-11(17)12(18)5-8/h1-7,16-18H/b14-6+
SMILES	c1cc(c(cc1/C=C/1C(=O)c2ccc(cc2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	270.05	Volume:	265.186 ? Van der Waals volume.
Dense:	1.018	LogP:	2.141 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.195 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.133 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.547	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.352	Fsp³:	0.0
MCE-18:	34.0 ? 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:	0.84	Fluc inhibitor:	0.995 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.644 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.611 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.767	Promiscuous compounds:	0.594

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.916	MDCK Permeability:	-4.793
Pgp-inhibitor:	0.033	Pgp-substrate:	0.005
PAMPA:	0.613 ? 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):	0.143
20% Bioavailability (F20%):	0.898	30% Bioavailability (F30%):	0.976
50% Bioavailability (F50%):	0.992

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.12
Plasma Protein Binding (PPB):	93.059%	Volume Distribution (VD):	-0.391
Fu:	6.447% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.984
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.372
BSEP inhibitor:	0.362

ADMET: Metabolism

CYP1A2-inhibitor:	0.511	CYP1A2-substrate:	0.987
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.071
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.082	CYP2D6-substrate:	0.917
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.931
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.48 ? 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):

10.404

Half-life (T1/2):

1.35

ADMET: Toxicity

hERG Blockers:	0.092	hERG Blockers (10um):	0.567
Human Hepatotoxicity (H-HT):	0.604	Drug-induced Liver Injury (DILI):	0.424
AMES Toxicity:	0.641	Rat Oral Acute Toxicity:	0.43
Maximum Recommended Daily Dose:	0.804	Skin Sensitization:	0.989
Carcinogencity:	0.735	Eye Corrosion:	0.161
Eye Irritation:	0.99	Respiratory Toxicity:	0.277
Drug-induced Neurotoxicity:	0.101	Ototoxicity:	0.442
Hematotoxicity:	0.119	Drug-induced Nephrotoxicity:	0.107
Genotoxicity:	0.976	RPMI-8226 Immunitoxicity:	0.047
A549 Cytotoxicity:	0.74	Hek293 Cytotoxicity:	0.738
BCF:	1.185 ? 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:	4.275 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.061 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.773 ? 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]
NPO5220	Knema globularia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[35876169]
NPO5220	Knema globularia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30029	Rhus verniciflua	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22420	Lignum dalbergiae odoriferae rosewood	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15266	Cotinus sp.	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3354	Fomes officinalis	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3354	Fomes officinalis	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30029	Rhus verniciflua	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30476	Cotinus sp	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5220	Knema globularia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3354	Fomes officinalis	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5220	Knema globularia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15266	Cotinus sp.	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22420	Lignum dalbergiae odoriferae rosewood	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4916	Toxicodendron vernicifluum	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5220	Knema globularia	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3354	Fomes officinalis	Species	Coriolaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24559	Cotinus coggygria	Species	Anacardiaceae	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	15

Activity Type	# Activity
Individual protein	11
Protein-protein interaction	3
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT198	Individual protein	Vitamin D receptor	Homo sapiens	Potency	n.a.	79432.8	nM	PubChem BioAssay data set
NPT199	Individual protein	DNA polymerase kappa	Homo sapiens	Potency	n.a.	4744.4	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	8912.5	nM	PubChem BioAssay data set
NPT533	Protein-protein interaction	Runt-related transcription factor 1/Core-binding factor subunit beta	Homo sapiens	Potency	n.a.	31622.8	nM	PubChem BioAssay data set
NPT888	Individual protein	78 kDa glucose-regulated protein	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT46	Individual protein	Thyroid hormone receptor beta-1	Homo sapiens	Potency	=	50118.7	nM	PubChem BioAssay data set
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	25118.9	nM	PubChem BioAssay data set
NPT47	Individual protein	ATP-dependent DNA helicase Q1	Homo sapiens	Potency	=	19952.6	nM	PubChem BioAssay data set
NPT53	Individual protein	4'-phosphopantetheinyl transferase ffp	Bacillus subtilis	Potency	=	63095.7	nM	PubChem BioAssay data set
NPT442	Individual protein	Ferritin light chain	Equus caballus	Potency	=	39810.7	nM	PubChem BioAssay data set
NPT197	Protein-protein interaction	Menin/Histone-lysine N-methyltransferase MLL	Homo sapiens	Potency	=	22387.2	nM	PubChem BioAssay data set
NPT443	Individual protein	Histone acetyltransferase GCN5	Homo sapiens	Potency	n.a.	14125.4	nM	PubChem BioAssay data set
NPT47	Individual protein	ATP-dependent DNA helicase Q1	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT49	Individual protein	DNA-(apurinic or apyrimidinic site) lyase	Homo sapiens	Potency	n.a.	14125.4	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.	2818.4	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 NPC86847 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	25269
0.1-0.2	20015
0.2-0.3	4190
0.3-0.4	339
0.4-0.5	32
0.5-0.6	6
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC140840
0.814	Intermediate Similarity	NPC254841
0.7	Intermediate Similarity	NPC19545
0.6863	Remote Similarity	NPC304954
0.6735	Remote Similarity	NPC260582
0.6346	Remote Similarity	NPC233724
0.625	Remote Similarity	NPC189130
0.5962	Remote Similarity	NPC231758
0.5926	Remote Similarity	NPC195832
0.5769	Remote Similarity	NPC301178
0.5357	Remote Similarity	NPC95864
0.5323	Remote Similarity	NPC472582
0.5147	Remote Similarity	NPC48640

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC86847 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4242
0.1-0.2	4749
0.2-0.3	153
0.3-0.4	6
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