NPASS Compound

Natural Product: NPC476404

Natural Product ID	NPC476404
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	8-Hydroxy-2-[(1R)-1-Hydroxyethyl]-Naphtho[2,3-B]Furan-4,9-Dione
IUPAC Name	8-hydroxy-2-[(1R)-1-hydroxyethyl]benzo[f][1]benzofuran-4,9-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL596002
PubChem CID	14159820
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001634] Naphthofurans

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 29 31 0 0 0 0 0 0 0 0999 V2000 4.5915 -0.7163 -0.1773 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9072 0.6193 -0.0487 C 0 0 2 0 0 0 0 0 0 0 0 0 2.4486 0.3824 -0.0236 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6925 0.3589 1.1274 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3690 0.1136 0.8011 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3846 -0.0047 -0.5849 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6149 0.1599 -1.0088 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8964 -0.2715 -1.2382 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8987 -0.3810 -2.4897 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1081 -0.4019 -0.4563 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1174 -0.2835 0.9195 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8577 -0.0193 1.5819 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8423 0.0928 2.8392 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2686 -0.4067 1.6696 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4730 -0.6583 1.0478 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4582 -0.7763 -0.3336 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3035 -0.6516 -1.0742 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3807 -0.7850 -2.4585 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2740 1.5153 -1.0457 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4505 -0.5867 -0.8660 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9155 -1.5097 -0.5463 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0150 -1.0507 0.8051 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2363 1.0686 0.9095 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0163 0.5006 2.1438 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2357 -0.3089 2.7295 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3913 -0.7590 1.6181 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4142 -0.9769 -0.8389 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5959 -0.0136 -3.0728 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3258 1.1115 -1.9289 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 8 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 2 19 1 0 7 3 1 0 17 10 1 0 12 5 1 0 1 20 1 0 1 21 1 0 1 22 1 0 2 23 1 1 4 24 1 0 14 25 1 0 15 26 1 0 16 27 1 0 18 28 1 0 19 29 1 0 M END

Standard InCHIKey	CKCXAMWUYPZVFL-ZCFIWIBFSA-N
Standard InCHI	InChI=1S/C14H10O5/c1-6(15)10-5-8-12(17)7-3-2-4-9(16)11(7)13(18)14(8)19-10/h2-6,15-16H,1H3/t6-/m1/s1
SMILES	C[C@H](c1cc2c(o1)C(=O)c1c(C2=O)cccc1O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	258.05	Volume:	250.527 ? Van der Waals volume.
Dense:	1.03	LogP:	2.169 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.372 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.056 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	87.74 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.695	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.14	Fsp³:	0.143
MCE-18:	54.0 ? 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:	0	PAINS Alert:	1
Colloidal aggregators:	0.152	Fluc inhibitor:	0.569 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.551 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.465 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.366	Promiscuous compounds:	0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.759	MDCK Permeability:	-4.711
Pgp-inhibitor:	0.923	Pgp-substrate:	0.02
PAMPA:	0.754 ? 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):	0.121
20% Bioavailability (F20%):	0.06	30% Bioavailability (F30%):	0.939
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.58
Plasma Protein Binding (PPB):	87.824%	Volume Distribution (VD):	0.352
Fu:	12.735% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.354
BSEP inhibitor:	0.961

ADMET: Metabolism

CYP1A2-inhibitor:	0.603	CYP1A2-substrate:	0.239
CYP2C19-inhibitor:	0.105	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.002
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.024	CYP3A4-substrate:	0.21
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.991
HLM stability:	0.094 ? 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):

4.93

Half-life (T1/2):

1.33

ADMET: Toxicity

hERG Blockers:	0.031	hERG Blockers (10um):	0.254
Human Hepatotoxicity (H-HT):	0.649	Drug-induced Liver Injury (DILI):	0.954
AMES Toxicity:	0.873	Rat Oral Acute Toxicity:	0.479
Maximum Recommended Daily Dose:	0.821	Skin Sensitization:	0.584
Carcinogencity:	0.915	Eye Corrosion:	0.0
Eye Irritation:	0.868	Respiratory Toxicity:	0.786
Drug-induced Neurotoxicity:	0.12	Ototoxicity:	0.309
Hematotoxicity:	0.282	Drug-induced Nephrotoxicity:	0.38
Genotoxicity:	0.987	RPMI-8226 Immunitoxicity:	0.261
A549 Cytotoxicity:	0.267	Hek293 Cytotoxicity:	0.388
BCF:	1.429 ? 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:	3.788 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.855 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.315 ? 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
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17950604]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	bark	n.a.	PMID[17950604]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	Brazilian	n.a.	PMID[19674905]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32044231]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	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
MIC	12
Activity	5
IC50	1

Activity Type	# Activity
Cell line	1
Organism	12
Others	5

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
NPT80	Cell line	Raji	Homo sapiens	Activity	=	60.0	%	PMID[16499318]
NPT3658	Organism	Bacillus mycoides	Bacillus mycoides	MIC	=	1.56	ug.mL-1	PubChem BioAssay data set
NPT3656	Organism	Paecilomyces variotii	Paecilomyces variotii	MIC	=	50.0	ug.mL-1	PMID[23987662]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	1.56	ug.mL-1	PubChem BioAssay data set
NPT312	Organism	Saccharomyces cerevisiae	Saccharomyces cerevisiae	MIC	=	3.13	ug.mL-1	PMID[20537903]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	25.0	ug.mL-1	PMID[24099364]
NPT3657	Organism	Cryptococcus albidus	Cryptococcus albidus	MIC	=	1.56	ug.mL-1	PMID[24087924]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	6.25	ug.mL-1	PMID[20403645]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MIC	=	25.0	ug.mL-1	PMID[24099364]
NPT3086	Organism	Penicillium expansum	Penicillium expansum	MIC	=	50.0	ug.mL-1	PMID[23987662]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	100.0	ug.mL-1	PMID[25856683]
NPT18	Organism	Pseudomonas aeruginosa	Pseudomonas aeruginosa	MIC	>	100.0	ug.mL-1	PMID[25856683]
NPT3608	Organism	Salmonella enteritidis	Salmonella enterica subsp. enterica serovar Enteritidis	MIC	>	100.0	ug.mL-1	PMID[25856683]
NPT2	Others	Unspecified	n.a.	Activity	=	4.2	%	PMID[12880308]
NPT2	Others	Unspecified	n.a.	Activity	=	20.4	%	PMID[18729518]
NPT2	Others	Unspecified	n.a.	Activity	=	52.5	%	PMID[16499318]
NPT2	Others	Unspecified	n.a.	Activity	=	76.3	%	PMID[16499318]
NPT2	Others	Unspecified	n.a.	IC50	=	201100.0	nM	PMID[16499318]

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 NPC476404 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	21009
0.1-0.2	27026
0.2-0.3	1693
0.3-0.4	106
0.4-0.5	15
0.5-0.6	0
0.6-0.7	3
0.7-0.8	0
0.8-0.85	3
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	NPC294300
1.0	High Similarity	NPC317900
0.8222	Intermediate Similarity	NPC473282
0.8222	Intermediate Similarity	NPC104380
0.8222	Intermediate Similarity	NPC217602
0.7391	Intermediate Similarity	NPC252208
0.6889	Remote Similarity	NPC471613
0.6889	Remote Similarity	NPC289955
0.6	Remote Similarity	NPC226578

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476404 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3069
0.1-0.2	5906
0.2-0.3	172
0.3-0.4	1
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