NPASS Compound

Natural Product: NPC151473

Natural Product ID	NPC151473
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1,3,5,6-Tetrahydroxy-8-Methylxanthone
IUPAC Name	3,4,6,8-tetrahydroxy-1-methylxanthen-9-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465184
PubChem CID	10401107
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 -2.3905 -2.4503 -0.4612 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2509 -0.9805 -0.2259 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3603 -0.1662 -0.1292 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2443 1.1900 0.0875 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0133 1.7984 0.2182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8980 0.9918 0.1229 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0124 -0.3796 -0.0962 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1429 -1.1257 -0.1808 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0724 -2.3480 -0.3752 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3813 -0.5062 -0.0481 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5676 -1.2318 -0.1286 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7995 -0.6160 0.0033 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8301 0.7439 0.2182 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6487 1.4458 0.2951 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4091 0.8623 0.1681 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2861 1.5401 0.2428 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0821 1.3508 0.3492 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4637 -2.6067 -0.3480 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8884 3.1714 0.4378 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3759 1.9917 0.1815 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4820 -2.6758 -0.5273 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0144 -3.0485 0.3972 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9658 -2.7668 -1.4295 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3282 -0.6447 -0.2320 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7029 -1.2049 -0.0638 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6941 2.5047 0.4630 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3903 1.6750 1.2613 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4788 -2.9818 -1.2970 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3949 3.5432 1.2537 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3303 2.9242 -0.1570 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 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 13 17 1 0 11 18 1 0 5 19 1 0 4 20 1 0 7 2 1 0 15 10 1 0 16 6 1 0 1 21 1 0 1 22 1 0 1 23 1 0 3 24 1 0 12 25 1 0 14 26 1 0 17 27 1 0 18 28 1 0 19 29 1 0 20 30 1 0 M END

Standard InCHIKey	REMPMEBGVJJOHV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C14H10O6/c1-5-2-8(17)12(18)14-10(5)13(19)11-7(16)3-6(15)4-9(11)20-14/h2-4,15-18H,1H3
SMILES	Cc1cc(c(c2c1c(=O)c1c(cc(cc1o2)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	274.05	Volume:	259.317 ? Van der Waals volume.
Dense:	1.057	LogP:	1.465 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.673 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.001 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	17.0
TPSA:	111.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.369	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.72	Fsp³:	0.071
MCE-18:	19.0 ? 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:	1
Colloidal aggregators:	0.796	Fluc inhibitor:	0.486 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.855 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.328 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.505	Promiscuous compounds:	0.539

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.465	MDCK Permeability:	-4.861
Pgp-inhibitor:	0.021	Pgp-substrate:	0.59
PAMPA:	0.447 ? 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):	0.046
20% Bioavailability (F20%):	0.543	30% Bioavailability (F30%):	0.96
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018	MRP1:	0.775
Plasma Protein Binding (PPB):	97.131%	Volume Distribution (VD):	-0.684
Fu:	2.481% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.719
OATP1B3 inhibitor:	0.892	BCRP inhibitor:	0.955
BSEP inhibitor:	0.347

ADMET: Metabolism

CYP1A2-inhibitor:	0.42	CYP1A2-substrate:	0.085
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.656
CYP2C9-inhibitor:	0.566	CYP2C9-substrate:	0.019
CYP2D6-inhibitor:	0.972	CYP2D6-substrate:	0.989
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.942 ? 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):

6.278

Half-life (T1/2):

1.476

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.437
Human Hepatotoxicity (H-HT):	0.409	Drug-induced Liver Injury (DILI):	0.849
AMES Toxicity:	0.727	Rat Oral Acute Toxicity:	0.538
Maximum Recommended Daily Dose:	0.775	Skin Sensitization:	0.797
Carcinogencity:	0.687	Eye Corrosion:	0.34
Eye Irritation:	0.998	Respiratory Toxicity:	0.729
Drug-induced Neurotoxicity:	0.006	Ototoxicity:	0.098
Hematotoxicity:	0.052	Drug-induced Nephrotoxicity:	0.014
Genotoxicity:	0.979	RPMI-8226 Immunitoxicity:	0.034
A549 Cytotoxicity:	0.419	Hek293 Cytotoxicity:	0.554
BCF:	1.237 ? 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:	3.924 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.727 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.29 ? 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
NPO1865	Penicillium raistrickii	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748377]
NPO1865	Penicillium raistrickii	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6825	Clethra barbinervis	Species	Clethraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1865	Penicillium raistrickii	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO556	Hypericum attenuatum	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4553	Oxycorynia fascicularis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO5580	Alstonia glaucescens	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4265	Trichocereus pachanoi	Species	Cactaceae	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
IZ	2

Activity Type	# Activity
Organism	2

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
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	IZ	=	12.0	mm	PMID[9748377]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	11.0	mm	PMID[9748377]

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 NPC151473 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	32465
0.1-0.2	14994
0.2-0.3	1898
0.3-0.4	424
0.4-0.5	61
0.5-0.6	11
0.6-0.7	3
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
0.7021	Intermediate Similarity	NPC275734
0.6296	Remote Similarity	NPC486841
0.6078	Remote Similarity	NPC202157
0.6078	Remote Similarity	NPC196277
0.5593	Remote Similarity	NPC274730
0.549	Remote Similarity	NPC61620
0.549	Remote Similarity	NPC194856
0.5357	Remote Similarity	NPC202595
0.5246	Remote Similarity	NPC329091
0.5185	Remote Similarity	NPC272721
0.5167	Remote Similarity	NPC89474
0.5135	Remote Similarity	NPC120102
0.5094	Remote Similarity	NPC169479
0.5094	Remote Similarity	NPC276930
0.5085	Remote Similarity	NPC487785

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC151473 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6172
0.1-0.2	2935
0.2-0.3	38
0.3-0.4	3
0.4-0.5	2
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