NPASS Compound

Natural Product: NPC252208

Natural Product ID	NPC252208
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Acetyl-8-Hydroxynaphtho-[2,3-B]Furan-4,9-Dione
IUPAC Name	2-acetyl-8-hydroxybenzo[f][1]benzofuran-4,9-dione
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL493650
PubChem CID	9881541
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 27 29 0 0 0 0 0 0 0 0999 V2000 5.0765 0.1364 0.0318 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1115 -0.9583 -0.1353 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5148 -2.1319 -0.3155 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6884 -0.6779 -0.0912 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1361 0.5696 0.1005 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7617 0.4293 0.0800 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5273 -0.9133 -0.1256 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6936 -1.5258 -0.2204 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8399 -1.3990 -0.1990 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1205 -2.6076 -0.3841 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9444 -0.4271 -0.0492 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7081 0.9129 0.1561 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3192 1.3934 0.2287 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1309 2.6070 0.4146 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7669 1.8011 0.2930 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0618 1.3406 0.2234 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3123 0.0047 0.0188 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2638 -0.8751 -0.1169 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4783 -2.2243 -0.3236 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4092 0.5694 -0.9338 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6130 0.9603 0.6215 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9981 -0.1525 0.5737 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6431 1.5214 0.2460 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5314 2.8616 0.4554 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8913 2.0159 0.3276 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3345 -0.3916 -0.0412 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4701 -2.8392 0.4592 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 7 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 12 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 8 4 1 0 18 11 1 0 13 6 1 0 1 20 1 0 1 21 1 0 1 22 1 0 5 23 1 0 15 24 1 0 16 25 1 0 17 26 1 0 19 27 1 0 M END

Standard InCHIKey	MYDAXHYLQBNETF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H8O5/c1-6(15)10-5-8-12(17)7-3-2-4-9(16)11(7)13(18)14(8)19-10/h2-5,16H,1H3
SMILES	CC(=O)c1cc2c(o1)C(=O)c1c(C2=O)cccc1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	256.04	Volume:	247.89 ? Van der Waals volume.
Dense:	1.033	LogP:	2.475 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.572 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.438 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	84.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.673	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.573	Fsp³:	0.071
MCE-18:	36.0 ? 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:	0.141	Fluc inhibitor:	0.557 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.806 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.472 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.573	Promiscuous compounds:	0.119

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.695	MDCK Permeability:	-4.638
Pgp-inhibitor:	0.857	Pgp-substrate:	0.048
PAMPA:	0.423 ? 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):	0.31
20% Bioavailability (F20%):	0.244	30% Bioavailability (F30%):	0.833
50% Bioavailability (F50%):	0.909

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014	MRP1:	0.396
Plasma Protein Binding (PPB):	95.34%	Volume Distribution (VD):	0.269
Fu:	5.15% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.906
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.386
BSEP inhibitor:	0.816

ADMET: Metabolism

CYP1A2-inhibitor:	0.805	CYP1A2-substrate:	0.434
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.018	CYP2D6-substrate:	0.008
CYP3A4-inhibitor:	0.013	CYP3A4-substrate:	0.033
CYP2B6-substrate:	0.004	CYP2C8-inhibitor:	0.995
HLM stability:	0.612 ? 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):

4.648

Half-life (T1/2):

0.882

ADMET: Toxicity

hERG Blockers:	0.045	hERG Blockers (10um):	0.351
Human Hepatotoxicity (H-HT):	0.703	Drug-induced Liver Injury (DILI):	0.97
AMES Toxicity:	0.927	Rat Oral Acute Toxicity:	0.478
Maximum Recommended Daily Dose:	0.281	Skin Sensitization:	0.582
Carcinogencity:	0.94	Eye Corrosion:	0.002
Eye Irritation:	0.918	Respiratory Toxicity:	0.733
Drug-induced Neurotoxicity:	0.137	Ototoxicity:	0.248
Hematotoxicity:	0.774	Drug-induced Nephrotoxicity:	0.328
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.268
A549 Cytotoxicity:	0.311	Hek293 Cytotoxicity:	0.397
BCF:	1.495 ? 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:	3.89 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.83 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.399 ? 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]
NPO3751	Orthantha lutea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12083	Hydnellum zonatum	Species	Thelephoraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO487	Tabebuia avellanedae	Species	Bignoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3751	Orthantha lutea	n.a.	n.a.	n.a.	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	2
Activity	6
EC50	3

Activity Type	# Activity
Cell line	6
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
NPT941	Cell line	HaCaT	Homo sapiens	IC50	=	300.0	nM	PMID[10479319]
NPT941	Cell line	HaCaT	Homo sapiens	Activity	=	346.0	mU	PMID[10479319]
NPT83	Cell line	MCF7	Homo sapiens	EC50	=	2610.0	nM	PMID[19674905]
NPT306	Cell line	PC-3	Homo sapiens	EC50	=	3000.0	nM	PMID[19674905]
NPT81	Cell line	A549	Homo sapiens	EC50	=	4310.0	nM	PMID[19674905]
NPT80	Cell line	Raji	Homo sapiens	Activity	=	70.0	%	PMID[19674905]
NPT2	Others	Unspecified	n.a.	Activity	=	0.0	%	PMID[19674905]
NPT2	Others	Unspecified	n.a.	Activity	=	8.3	%	PMID[19674905]
NPT2	Others	Unspecified	n.a.	Activity	=	27.5	%	PMID[19674905]
NPT2	Others	Unspecified	n.a.	Activity	=	60.3	%	PMID[19674905]
NPT2	Others	Unspecified	n.a.	IC50	=	40100.0	nM	PMID[19674905]

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 NPC252208 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	24374
0.1-0.2	23553
0.2-0.3	1794
0.3-0.4	105
0.4-0.5	22
0.5-0.6	1
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	0

Similarity Score	Similarity Level	Natural Product ID
0.814	Intermediate Similarity	NPC226578
0.7391	Intermediate Similarity	NPC476404
0.7391	Intermediate Similarity	NPC294300
0.7391	Intermediate Similarity	NPC317900
0.6512	Remote Similarity	NPC265181
0.6	Remote Similarity	NPC473282
0.6	Remote Similarity	NPC104380
0.6	Remote Similarity	NPC217602
0.5122	Remote Similarity	NPC375356

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC252208 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3196
0.1-0.2	5810
0.2-0.3	140
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6512	Remote Similarity	NPD1471	Phase 3

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