NPASS Compound

Natural Product: NPC263166

Natural Product ID	NPC263166
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	NJTOSCMFMNLPNQ-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	86168207
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 28 30 0 0 0 0 0 0 0 0999 V2000 -4.2115 1.2859 0.4653 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8160 1.1094 0.5958 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1523 0.2407 -0.2833 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8136 -0.4516 -1.2759 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1648 -1.3114 -2.1479 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7986 -1.4508 -1.9800 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1055 -0.7737 -0.9979 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2613 -0.9130 -0.8298 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9237 -1.6734 -1.5793 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9485 -0.2319 0.1558 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3096 -0.3817 0.3100 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9404 0.3271 1.3147 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2032 1.1592 2.1320 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8440 1.2956 1.9622 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2035 0.5976 0.9679 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1110 0.7231 0.7961 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7692 0.0785 -0.1385 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0500 -1.2293 -0.5251 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8010 0.4979 0.9638 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4523 2.2356 1.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5026 1.4648 -0.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8960 -0.3148 -1.3772 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7282 -1.8311 -2.9095 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2621 -2.1077 -2.6364 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0205 0.2192 1.4503 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7251 1.7142 2.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2578 1.9414 2.5930 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8970 -2.2199 -0.3783 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 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 11 18 1 0 17 3 1 0 17 7 2 0 15 10 1 0 1 19 1 0 1 20 1 0 1 21 1 0 4 22 1 0 5 23 1 0 6 24 1 0 12 25 1 0 13 26 1 0 14 27 1 0 18 28 1 0 M END

Standard InCHIKey	NJTOSCMFMNLPNQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O4/c1-17-11-7-2-4-8-13(16)12-9(15)5-3-6-10(12)18-14(8)11/h2-7,15H,1H3
SMILES	COc1cccc2c(=O)c3c(cccc3oc12)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	242.06	Volume:	241.737 ? Van der Waals volume.
Dense:	1.001	LogP:	2.5 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.54 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.078 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	59.67 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.666	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.068	Fsp³:	0.071
MCE-18:	16.0 ? 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:	0
Colloidal aggregators:	0.144	Fluc inhibitor:	0.655 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.793 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.391 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.673	Promiscuous compounds:	0.485

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.79	MDCK Permeability:	-4.684
Pgp-inhibitor:	0.78	Pgp-substrate:	0.42
PAMPA:	0.224 ? 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):	0.027
20% Bioavailability (F20%):	0.173	30% Bioavailability (F30%):	0.448
50% Bioavailability (F50%):	0.842

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.151	MRP1:	0.56
Plasma Protein Binding (PPB):	98.455%	Volume Distribution (VD):	-0.502
Fu:	1.657% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.65
OATP1B3 inhibitor:	0.921	BCRP inhibitor:	0.909
BSEP inhibitor:	0.981

ADMET: Metabolism

CYP1A2-inhibitor:	0.476	CYP1A2-substrate:	0.578
CYP2C19-inhibitor:	0.013	CYP2C19-substrate:	0.168
CYP2C9-inhibitor:	0.978	CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.88	CYP2D6-substrate:	0.706
CYP3A4-inhibitor:	0.046	CYP3A4-substrate:	0.947
CYP2B6-substrate:	0.02	CYP2C8-inhibitor:	0.849
HLM stability:	0.493 ? 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):

4.719

Half-life (T1/2):

0.815

ADMET: Toxicity

hERG Blockers:	0.069	hERG Blockers (10um):	0.422
Human Hepatotoxicity (H-HT):	0.47	Drug-induced Liver Injury (DILI):	0.87
AMES Toxicity:	0.697	Rat Oral Acute Toxicity:	0.555
Maximum Recommended Daily Dose:	0.503	Skin Sensitization:	0.494
Carcinogencity:	0.826	Eye Corrosion:	0.517
Eye Irritation:	0.99	Respiratory Toxicity:	0.777
Drug-induced Neurotoxicity:	0.122	Ototoxicity:	0.115
Hematotoxicity:	0.234	Drug-induced Nephrotoxicity:	0.126
Genotoxicity:	0.696	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.123	Hek293 Cytotoxicity:	0.264
BCF:	1.159 ? 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:	3.913 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.721 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.435 ? 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
NPO18760	Euphorbia parviflora	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9895	Bupleurum tenue	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2261	Chromodoris petechialis	Species	Chromodorididae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8667	Azara microphylla	Species	Salicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9762	Lenzites sepiaria	Species	Coriolaceae	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
Activity	2
PC50	2

Activity Type	# Activity
Cell line	4

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
NPT461	Cell line	PANC-1	Homo sapiens	Activity	n.a.	n.a.	n.a.	PMID[34008971]
NPT461	Cell line	PANC-1	Homo sapiens	PC50	=	61.0	uM	PMID[34008971]

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 NPC263166 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	27508
0.1-0.2	18610
0.2-0.3	3193
0.3-0.4	466
0.4-0.5	66
0.5-0.6	12
0.6-0.7	2
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
0.6731	Remote Similarity	NPC603670
0.6122	Remote Similarity	NPC602252
0.5893	Remote Similarity	NPC271232
0.5769	Remote Similarity	NPC59551
0.5741	Remote Similarity	NPC603894
0.5714	Remote Similarity	NPC149614
0.5714	Remote Similarity	NPC46941
0.5472	Remote Similarity	NPC9985
0.5469	Remote Similarity	NPC57674
0.5455	Remote Similarity	NPC610896
0.537	Remote Similarity	NPC601929
0.5357	Remote Similarity	NPC608745
0.5283	Remote Similarity	NPC18457
0.5088	Remote Similarity	NPC209278

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC263166 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4271
0.1-0.2	4691
0.2-0.3	184
0.3-0.4	4
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