NPASS Compound

Natural Product: NPC101996

Natural Product ID	NPC101996
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Alloathyriol
IUPAC Name	1,3,6-trihydroxy-7-methoxyxanthen-9-one
Synonyms	Alloathyriol
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL482243
PubChem CID	44575387
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 30 32 0 0 0 0 0 0 0 0999 V2000 4.5761 1.2456 0.8464 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0682 1.4031 -0.4599 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7445 1.0561 -0.7272 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9351 0.5642 0.2675 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6271 0.2307 -0.0355 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0812 0.3648 -1.2939 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9208 0.8673 -2.2935 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2239 1.2007 -1.9965 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0780 1.7018 -2.9720 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1632 0.0421 -1.5596 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9495 -0.4292 -0.6205 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4697 -0.5907 0.6661 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1705 -0.2614 0.9754 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2990 -0.3976 2.1437 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2749 -1.0827 1.6668 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7508 -1.2246 2.9294 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5738 -1.4072 1.3384 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1101 -1.2693 0.0768 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2774 -0.7737 -0.9036 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4314 -1.6094 -0.2159 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8728 1.6557 1.6242 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5245 1.8151 0.9757 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7832 0.1808 1.0313 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2810 0.4282 1.2762 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5222 0.9807 -3.2765 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9196 1.3763 -3.9258 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2717 -2.0667 3.2255 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2286 -1.7954 2.1030 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6289 -0.6368 -1.9229 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1566 -1.5683 0.4778 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 6 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 12 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 2 0 18 20 1 0 8 3 1 0 19 11 1 0 13 5 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 7 25 1 0 9 26 1 0 16 27 1 0 17 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	CLZONBOPXUGYNY-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O6/c1-19-11-4-7-10(5-8(11)16)20-12-3-6(15)2-9(17)13(12)14(7)18/h2-5,15-17H,1H3
SMILES	COc1cc2c(cc1O)oc1c(c2=O)c(O)cc(c1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.05	Volume:	259.317 ? Van der Waals volume.
Dense:	1.057	LogP:	1.705 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.953 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.916 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	17.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.587	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.368	Fsp³:	0.071
MCE-18:	18.0 ? 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:	0.615	Fluc inhibitor:	0.753 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.915 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.591 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.49	Promiscuous compounds:	0.864

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.057	MDCK Permeability:	-4.806
Pgp-inhibitor:	0.143	Pgp-substrate:	0.793
PAMPA:	0.061 ? 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):	0.017
20% Bioavailability (F20%):	0.131	30% Bioavailability (F30%):	0.7
50% Bioavailability (F50%):	0.978

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.024	MRP1:	0.805
Plasma Protein Binding (PPB):	96.327%	Volume Distribution (VD):	-0.597
Fu:	3.411% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.821
OATP1B3 inhibitor:	0.974	BCRP inhibitor:	0.989
BSEP inhibitor:	0.825

ADMET: Metabolism

CYP1A2-inhibitor:	0.973	CYP1A2-substrate:	0.131
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.023
CYP2C9-inhibitor:	0.189	CYP2C9-substrate:	0.556
CYP2D6-inhibitor:	0.986	CYP2D6-substrate:	0.995
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.519 ? 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):

2.427

Half-life (T1/2):

1.603

ADMET: Toxicity

hERG Blockers:	0.073	hERG Blockers (10um):	0.488
Human Hepatotoxicity (H-HT):	0.401	Drug-induced Liver Injury (DILI):	0.817
AMES Toxicity:	0.681	Rat Oral Acute Toxicity:	0.556
Maximum Recommended Daily Dose:	0.82	Skin Sensitization:	0.565
Carcinogencity:	0.825	Eye Corrosion:	0.614
Eye Irritation:	0.998	Respiratory Toxicity:	0.808
Drug-induced Neurotoxicity:	0.033	Ototoxicity:	0.067
Hematotoxicity:	0.074	Drug-induced Nephrotoxicity:	0.028
Genotoxicity:	0.947	RPMI-8226 Immunitoxicity:	0.057
A549 Cytotoxicity:	0.251	Hek293 Cytotoxicity:	0.68
BCF:	0.988 ? 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:	3.494 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.314 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.698 ? 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
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	xylem	n.a.	PMID[14600386]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	fruits	n.a.	n.a.	PMID[15787435]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	roots	n.a.	n.a.	PMID[16989524]
NPO32808	cratoxylum formosum ssp. pruniflorum	Species	Hypericaceae	Eukaryota	stems	n.a.	n.a.	PMID[20608716]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	rhizome	n.a.	PMID[22863942]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	aerial parts	n.a.	n.a.	PMID[24042007]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38838926]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO32808	cratoxylum formosum ssp. pruniflorum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO21424	Garcinia xanthochymus	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27260	Polygala tenuifolia	Species	Polygalaceae	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
MIC	1

Activity Type	# Activity
Cell line	3
Organism	1

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
NPT660	Cell line	SW480	Homo sapiens	IC50	=	117000.0	nM	PMID[17190448]
NPT34	Cell line	BV-2	Mus musculus	IC50	>	100000.0	nM	PMID[20439614]
NPT34	Cell line	BV-2	Mus musculus	Inhibition	>	80.0	%	PMID[20961068]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	4.0	ug.mL-1	PMID[35308024]

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
n.a.	n.a.	LogP	=	1.74	n.a.	PMID[35308024]

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 NPC101996 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	31260
0.1-0.2	15317
0.2-0.3	2629
0.3-0.4	529
0.4-0.5	102
0.5-0.6	10
0.6-0.7	4
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
0.7273	Intermediate Similarity	NPC483011
0.72	Intermediate Similarity	NPC179183
0.7059	Intermediate Similarity	NPC14786
0.6346	Remote Similarity	NPC265251
0.6154	Remote Similarity	NPC292214
0.6038	Remote Similarity	NPC161277
0.6	Remote Similarity	NPC194856
0.5882	Remote Similarity	NPC239495
0.5818	Remote Similarity	NPC604806
0.5577	Remote Similarity	NPC169479
0.5484	Remote Similarity	NPC241904
0.5283	Remote Similarity	NPC275734
0.5224	Remote Similarity	NPC183036
0.5179	Remote Similarity	NPC206238
0.5091	Remote Similarity	NPC202157
0.5091	Remote Similarity	NPC196277
0.5091	Remote Similarity	NPC272721

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC101996 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5950
0.1-0.2	3128
0.2-0.3	65
0.3-0.4	7
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