NPASS Compound

Natural Product: NPC200221

Natural Product ID	NPC200221
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Hydroxy-1-Methoxyxanthone
IUPAC Name	2-hydroxy-1-methoxyxanthen-9-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1923834
PubChem CID	10399460
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 -2.6314 -2.2135 -0.5968 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4277 -1.2862 0.4567 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9954 0.0022 0.2674 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8539 1.0556 0.0623 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3345 2.3309 -0.1213 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9874 2.5951 -0.1079 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1214 1.5228 0.1006 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6469 0.2601 0.2820 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2191 -0.7875 0.4868 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1773 -1.9767 0.6619 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5694 -0.4946 0.4959 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4809 -1.5289 0.7004 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8239 -1.2486 0.7111 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2951 0.0330 0.5244 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4221 1.0767 0.3200 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0643 0.7914 0.3094 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1708 1.7400 0.1195 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2014 0.8211 0.0441 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9361 -2.0581 -1.4466 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6526 -2.1211 -1.0226 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4746 -3.2273 -0.1782 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0076 3.1832 -0.2864 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5811 3.5985 -0.2525 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0638 -2.5093 0.8409 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4934 -2.1041 0.8768 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3843 0.1952 0.5436 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7481 2.0944 0.1697 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7057 0.2556 0.7124 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 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 4 18 1 0 8 3 1 0 16 11 1 0 17 7 1 0 1 19 1 0 1 20 1 0 1 21 1 0 5 22 1 0 6 23 1 0 12 24 1 0 13 25 1 0 14 26 1 0 15 27 1 0 18 28 1 0 M END

Standard InCHIKey	ATPZBKJDXXSOFC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O4/c1-17-14-9(15)6-7-11-12(14)13(16)8-4-2-3-5-10(8)18-11/h2-7,15H,1H3
SMILES	COc1c(ccc2c1c(=O)c1ccccc1o2)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	242.06	Volume:	241.737 ? Van der Waals volume.
Dense:	1.001	LogP:	2.429 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.437 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.811 ? 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:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.118	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:	1	PAINS Alert:	0
Colloidal aggregators:	0.169	Fluc inhibitor:	0.845 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.769 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.525 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.642	Promiscuous compounds:	0.386

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.806	MDCK Permeability:	-4.652
Pgp-inhibitor:	0.398	Pgp-substrate:	0.105
PAMPA:	0.299 ? 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):	0.098
20% Bioavailability (F20%):	0.449	30% Bioavailability (F30%):	0.781
50% Bioavailability (F50%):	0.96

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.874
Plasma Protein Binding (PPB):	91.114%	Volume Distribution (VD):	-0.329
Fu:	9.871% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.928
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.954
BSEP inhibitor:	0.927

ADMET: Metabolism

CYP1A2-inhibitor:	0.975	CYP1A2-substrate:	0.902
CYP2C19-inhibitor:	0.239	CYP2C19-substrate:	0.59
CYP2C9-inhibitor:	0.983	CYP2C9-substrate:	0.01
CYP2D6-inhibitor:	0.967	CYP2D6-substrate:	0.415
CYP3A4-inhibitor:	0.012	CYP3A4-substrate:	0.239
CYP2B6-substrate:	0.52	CYP2C8-inhibitor:	0.034
HLM stability:	0.533 ? 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):

6.306

Half-life (T1/2):

1.209

ADMET: Toxicity

hERG Blockers:	0.093	hERG Blockers (10um):	0.479
Human Hepatotoxicity (H-HT):	0.5	Drug-induced Liver Injury (DILI):	0.806
AMES Toxicity:	0.631	Rat Oral Acute Toxicity:	0.473
Maximum Recommended Daily Dose:	0.408	Skin Sensitization:	0.574
Carcinogencity:	0.818	Eye Corrosion:	0.446
Eye Irritation:	0.987	Respiratory Toxicity:	0.745
Drug-induced Neurotoxicity:	0.214	Ototoxicity:	0.125
Hematotoxicity:	0.252	Drug-induced Nephrotoxicity:	0.153
Genotoxicity:	0.451	RPMI-8226 Immunitoxicity:	0.065
A549 Cytotoxicity:	0.133	Hek293 Cytotoxicity:	0.272
BCF:	1.13 ? 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:	3.826 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.764 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.379 ? 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
NPO40174	Kielmeyera variabilis	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26900954]
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
MIC	12

Activity Type	# Activity
Organism	12

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
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	31.3	ug.mL-1	PMID[22014830]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	125.0	ug.mL-1	PMID[22014830]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	=	15.6	ug.mL-1	PMID[22014830]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	64.0	ug.mL-1	PMID[26900954]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	128.0	ug.mL-1	PMID[26900954]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	32.0	ug.mL-1	PMID[26900954]
NPT314	Organism	Bacillus cereus	Bacillus cereus	MIC	=	31.3	ug.mL-1	PMID[22014830]
NPT1140	Organism	Escherichia coli ATCC 8739	Escherichia coli ATCC 8739	MIC	=	125.0	ug.mL-1	PMID[22014830]
NPT1121	Organism	Moraxella catarrhalis	Moraxella catarrhalis	MIC	=	125.0	ug.mL-1	PMID[22014830]
NPT1101	Organism	Staphylococcus aureus subsp. aureus RN4220	Staphylococcus aureus subsp. aureus RN4220	MIC	=	64.0	ug.mL-1	PMID[26900954]

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 NPC200221 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	28642
0.1-0.2	17764
0.2-0.3	3078
0.3-0.4	309
0.4-0.5	41
0.5-0.6	15
0.6-0.7	7
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
0.7143	Intermediate Similarity	NPC611763
0.6939	Remote Similarity	NPC161277
0.64	Remote Similarity	NPC292214
0.64	Remote Similarity	NPC92564
0.6327	Remote Similarity	NPC608827
0.6275	Remote Similarity	NPC608745
0.6078	Remote Similarity	NPC610896
0.6038	Remote Similarity	NPC120537
0.5849	Remote Similarity	NPC294502
0.5849	Remote Similarity	NPC271779
0.5833	Remote Similarity	NPC278787
0.5769	Remote Similarity	NPC145673
0.5769	Remote Similarity	NPC17055
0.5636	Remote Similarity	NPC285144
0.56	Remote Similarity	NPC605893
0.5556	Remote Similarity	NPC88645
0.551	Remote Similarity	NPC601623
0.551	Remote Similarity	NPC602252
0.549	Remote Similarity	NPC231013
0.5476	Remote Similarity	NPC475269
0.5476	Remote Similarity	NPC35744
0.537	Remote Similarity	NPC209278
0.52	Remote Similarity	NPC606736

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC200221 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4389
0.1-0.2	4537
0.2-0.3	216
0.3-0.4	8
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