NPASS Compound

Natural Product: NPC278787

Natural Product ID	NPC278787
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Hydroxyxanthen-9-One
IUPAC Name	2-hydroxyxanthen-9-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL185960
PubChem CID	74708
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 24 26 0 0 0 0 0 0 0 0999 V2000 -4.6675 -0.0122 0.6531 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3745 -0.2206 0.2166 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1839 -1.0704 -0.8588 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8925 -1.2703 -1.2847 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7848 -0.6643 -0.6903 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0201 0.1735 0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3075 0.3994 0.8338 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0748 0.7869 0.9816 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0944 1.5607 1.9601 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3134 0.4944 0.4487 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4966 -0.3589 -0.6299 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4255 -0.9021 -1.1518 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7590 -0.6291 -1.1385 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8610 -0.0424 -0.5673 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7071 0.8093 0.5053 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4474 1.0723 1.0048 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1931 0.7926 0.3278 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0238 -1.5539 -1.3392 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6766 -1.9343 -2.1342 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4559 1.0641 1.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8737 -1.2961 -1.9777 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8739 -0.2169 -0.9231 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5623 1.2822 0.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2800 1.7359 1.8470 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 6 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 7 2 1 0 16 10 1 0 12 5 1 0 1 17 1 0 3 18 1 0 4 19 1 0 7 20 1 0 13 21 1 0 14 22 1 0 15 23 1 0 16 24 1 0 M END

Standard InCHIKey	WSACHQJPCNOREV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H8O3/c14-8-5-6-12-10(7-8)13(15)9-3-1-2-4-11(9)16-12/h1-7,14H
SMILES	Oc1ccc2c(c1)c(=O)c1c(o2)cccc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	212.05	Volume:	215.65 ? Van der Waals volume.
Dense:	0.983	LogP:	2.667 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.808 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.357 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	17.0
TPSA:	50.44 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.583	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.854	Fsp³:	0.0
MCE-18:	15.0 ? 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:	0.274	Fluc inhibitor:	0.989 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.811 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.336 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.808	Promiscuous compounds:	0.809

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.836	MDCK Permeability:	-4.738
Pgp-inhibitor:	0.289	Pgp-substrate:	0.115
PAMPA:	0.674 ? 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):	0.042
20% Bioavailability (F20%):	0.197	30% Bioavailability (F30%):	0.461
50% Bioavailability (F50%):	0.829

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.191	MRP1:	0.539
Plasma Protein Binding (PPB):	86.835%	Volume Distribution (VD):	0.049
Fu:	12.373% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.659
OATP1B3 inhibitor:	0.941	BCRP inhibitor:	0.737
BSEP inhibitor:	0.926

ADMET: Metabolism

CYP1A2-inhibitor:	0.911	CYP1A2-substrate:	0.3
CYP2C19-inhibitor:	0.096	CYP2C19-substrate:	0.305
CYP2C9-inhibitor:	0.822	CYP2C9-substrate:	0.872
CYP2D6-inhibitor:	0.716	CYP2D6-substrate:	0.1
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	0.707
CYP2B6-substrate:	0.093	CYP2C8-inhibitor:	0.936
HLM stability:	0.513 ? 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):

7.092

Half-life (T1/2):

1.166

ADMET: Toxicity

hERG Blockers:	0.115	hERG Blockers (10um):	0.486
Human Hepatotoxicity (H-HT):	0.524	Drug-induced Liver Injury (DILI):	0.711
AMES Toxicity:	0.672	Rat Oral Acute Toxicity:	0.5
Maximum Recommended Daily Dose:	0.54	Skin Sensitization:	0.507
Carcinogencity:	0.823	Eye Corrosion:	0.594
Eye Irritation:	0.994	Respiratory Toxicity:	0.72
Drug-induced Neurotoxicity:	0.243	Ototoxicity:	0.119
Hematotoxicity:	0.195	Drug-induced Nephrotoxicity:	0.098
Genotoxicity:	0.72	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.121	Hek293 Cytotoxicity:	0.334
BCF:	1.333 ? 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:	4.147 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.905 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.607 ? 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
NPO18656	Iphigenia indica	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18656	Iphigenia indica	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO18656	Iphigenia indica	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO18656	Iphigenia indica	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO18656	Iphigenia indica	Species	Colchicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19688	Mangifera odorata	Species	Anacardiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27687	Peliosanthes sinica	Species	Asparagaceae	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
IC50	2
Inhibition	1
Activity	3
EC50	1

Activity Type	# Activity
Individual protein	3
Cell line	2
Organism	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT261	Individual protein	Monoamine oxidase A	Homo sapiens	IC50	=	3800.0	nM	PMID[15482934]
NPT741	Individual protein	Tyrosinase	Homo sapiens	IC50	=	5600.0	nM	PMID[33242700]
NPT741	Individual protein	Tyrosinase	Homo sapiens	Inhibition	=	89.32	%	PMID[33242700]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT520	Cell line	3T3-L1	Mus musculus	Activity	=	0.0	%	PMID[29626799]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT617	Organism	Danio rerio	Danio rerio	EC50	=	760.0	nM	PMID[29626799]
NPT617	Organism	Danio rerio	Danio rerio	Activity	=	0.0	%	PMID[29626799]

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 NPC278787 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	36738
0.1-0.2	11484
0.2-0.3	1460
0.3-0.4	119
0.4-0.5	34
0.5-0.6	11
0.6-0.7	7
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
0.8	Intermediate Similarity	NPC141549
0.7317	Intermediate Similarity	NPC159855
0.7073	Intermediate Similarity	NPC601623
0.6857	Remote Similarity	NPC475269
0.6857	Remote Similarity	NPC35744
0.6744	Remote Similarity	NPC18457
0.6667	Remote Similarity	NPC606736
0.6364	Remote Similarity	NPC600210
0.6279	Remote Similarity	NPC602252
0.617	Remote Similarity	NPC145673
0.587	Remote Similarity	NPC239495
0.587	Remote Similarity	NPC169479
0.5833	Remote Similarity	NPC200221
0.551	Remote Similarity	NPC292214
0.551	Remote Similarity	NPC17055
0.54	Remote Similarity	NPC206238
0.54	Remote Similarity	NPC608745
0.5294	Remote Similarity	NPC271779
0.5294	Remote Similarity	NPC88645
0.52	Remote Similarity	NPC610896
0.5192	Remote Similarity	NPC188167

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC278787 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6637
0.1-0.2	2407
0.2-0.3	96
0.3-0.4	10
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