NPASS Compound

Natural Product: NPC585468

Natural Product ID	NPC585468
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	[4-(5,7-dihydroxy-4-oxo-chromen-3-yl)phenyl] 2-hydroxy-6-methyl-benzoate
IUPAC Name	[4-(5,7-dihydroxy-4-oxo-chromen-3-yl)phenyl] 2-hydroxy-6-methyl-benzoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 46 49 0 0 0 0 0 0 0 0999 V2000 -5.0511 -1.7389 -0.1441 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7684 -0.4739 0.0573 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1414 -0.4446 -0.1850 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8358 0.7416 -0.0001 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1560 1.8779 0.4218 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7911 1.8045 0.6510 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1530 2.9609 1.0707 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0838 0.6384 0.4738 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6574 0.5344 0.7062 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2013 0.2221 1.8225 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7479 0.7803 -0.3121 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3762 0.6918 -0.1315 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7627 -0.5251 -0.3608 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5997 -0.6846 -0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3871 0.3799 0.1972 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8230 0.2107 0.3662 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4512 0.7295 1.4791 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7517 0.5977 1.6697 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5532 -0.0237 0.8403 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9116 -0.1332 1.0886 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6886 -0.7930 0.1839 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0598 -0.9063 0.4297 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1392 -1.3428 -0.9578 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8067 -1.2395 -1.2088 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2456 -1.7844 -2.3458 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0024 -0.5775 -0.3091 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6327 -0.4510 -0.5313 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1444 -0.9425 -1.5511 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7698 1.6160 0.4310 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5884 1.7485 0.2640 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3002 -2.4120 0.7072 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9669 -1.6379 -0.1664 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4067 -2.2722 -1.0634 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6783 -1.3248 -0.5137 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8897 0.8318 -0.1683 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6684 2.8200 0.5757 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0560 3.2359 2.0307 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3170 -1.4062 -0.6753 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1007 -1.6318 -0.3752 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8246 1.2601 2.2060 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3056 0.3096 1.9924 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3488 -1.8284 0.7858 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7723 -1.8507 -1.6430 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9224 -2.7425 -2.3828 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3848 2.4616 0.7452 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0282 2.7141 0.4529 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 1 0 6 8 2 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 1 0 21 23 2 0 23 24 1 0 24 25 1 0 24 26 2 0 26 27 1 0 27 28 2 0 15 29 1 0 29 30 2 0 8 2 1 0 30 12 1 0 27 16 1 0 26 19 1 0 1 31 1 0 1 32 1 0 1 33 1 0 3 34 1 0 4 35 1 0 5 36 1 0 7 37 1 0 13 38 1 0 14 39 1 0 17 40 1 0 20 41 1 0 22 42 1 0 23 43 1 0 25 44 1 0 29 45 1 0 30 46 1 0 M END

Standard InCHIKey	PFDFQVZVAQCSHC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C23H16O7/c1-12-3-2-4-17(25)20(12)23(28)30-15-7-5-13(6-8-15)16-11-29-19-10-14(24)9-18(26)21(19)22(16)27/h2-11,24-26H,1H3
SMILES	CC1=CC=CC(O)=C1C(=O)OC1=CC=C(C2=COC3=CC(O)=CC(O)=C3C2=O)C=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.09	Volume:	402.032 ? Van der Waals volume.
Dense:	1.005	LogP:	3.74 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.198 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.745 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	25.0
TPSA:	117.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	3.0	Rings:	4.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.347	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.504	Fsp³:	0.043
MCE-18:	24.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.949	Fluc inhibitor:	0.97 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.909 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.828 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.44	Promiscuous compounds:	0.422

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.162	MDCK Permeability:	-4.851
Pgp-inhibitor:	0.112	Pgp-substrate:	0.117
PAMPA:	0.509 ? 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):	0.018
20% Bioavailability (F20%):	0.222	30% Bioavailability (F30%):	0.802
50% Bioavailability (F50%):	0.962

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.047	MRP1:	0.408
Plasma Protein Binding (PPB):	97.768%	Volume Distribution (VD):	-0.566
Fu:	1.225% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.82
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.861
BSEP inhibitor:	0.868

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.963
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.665
CYP2C9-inhibitor:	0.999	CYP2C9-substrate:	0.984
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.91
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.259 ? 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):

1.418

Half-life (T1/2):

1.306

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.533
Human Hepatotoxicity (H-HT):	0.33	Drug-induced Liver Injury (DILI):	0.928
AMES Toxicity:	0.563	Rat Oral Acute Toxicity:	0.486
Maximum Recommended Daily Dose:	0.764	Skin Sensitization:	0.637
Carcinogencity:	0.518	Eye Corrosion:	0.008
Eye Irritation:	0.984	Respiratory Toxicity:	0.902
Drug-induced Neurotoxicity:	0.105	Ototoxicity:	0.195
Hematotoxicity:	0.066	Drug-induced Nephrotoxicity:	0.198
Genotoxicity:	0.954	RPMI-8226 Immunitoxicity:	0.084
A549 Cytotoxicity:	0.48	Hek293 Cytotoxicity:	0.649
BCF:	1.448 ? 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:	4.675 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.644 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.394 ? 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
NPO60656	Streptomyces sp. GW39/1530	Genus	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]

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

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

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 NPC585468 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	24215
0.1-0.2	22441
0.2-0.3	2707
0.3-0.4	375
0.4-0.5	86
0.5-0.6	31
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
0.6875	Remote Similarity	NPC294409
0.6875	Remote Similarity	NPC490701
0.5942	Remote Similarity	NPC200316
0.5938	Remote Similarity	NPC39426
0.5938	Remote Similarity	NPC608554
0.5857	Remote Similarity	NPC194653
0.5694	Remote Similarity	NPC104728
0.5634	Remote Similarity	NPC279668
0.5634	Remote Similarity	NPC278323
0.5556	Remote Similarity	NPC254702
0.5526	Remote Similarity	NPC233918
0.5522	Remote Similarity	NPC38065
0.5513	Remote Similarity	NPC107838
0.5507	Remote Similarity	NPC78341
0.5493	Remote Similarity	NPC309154
0.5385	Remote Similarity	NPC474052
0.5366	Remote Similarity	NPC156457
0.5316	Remote Similarity	NPC303197
0.5303	Remote Similarity	NPC193792
0.5263	Remote Similarity	NPC213659
0.5263	Remote Similarity	NPC326109
0.5256	Remote Similarity	NPC479305
0.5205	Remote Similarity	NPC481044
0.5139	Remote Similarity	NPC239363
0.5135	Remote Similarity	NPC142876
0.5135	Remote Similarity	NPC483637
0.5135	Remote Similarity	NPC264550
0.5128	Remote Similarity	NPC475705
0.5128	Remote Similarity	NPC268059
0.5125	Remote Similarity	NPC231763
0.5072	Remote Similarity	NPC87545
0.507	Remote Similarity	NPC116632
0.507	Remote Similarity	NPC35763

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC585468 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3241
0.1-0.2	5778
0.2-0.3	124
0.3-0.4	6
0.4-0.5	0
0.5-0.6	1
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
0.5938	Remote Similarity	NPD1510	Phase 2

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