NPASS Compound

Natural Product: NPC590405

Natural Product ID	NPC590405
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7-dihydroxy-3-(3-methoxyphenyl)chromen-4-one
IUPAC Name	5,7-dihydroxy-3-(3-methoxyphenyl)chromen-4-one
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 33 35 0 0 0 0 0 0 0 0999 V2000 5.8043 1.2918 0.5578 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4286 1.3658 0.3730 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5746 0.3016 0.1847 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9634 -1.0155 0.1512 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0191 -2.0259 -0.0459 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6689 -1.7220 -0.2120 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2777 -0.4001 -0.1785 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1426 -0.0366 -0.3503 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4776 1.0054 -1.1854 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7126 1.3881 -1.3901 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7167 0.7936 -0.8041 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0033 1.2262 -1.0456 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0386 0.5939 -0.4252 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3263 1.0205 -0.6616 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7786 -0.4738 0.4382 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4984 -0.9023 0.6768 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2643 -1.9560 1.5309 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4470 -0.2755 0.0595 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1552 -0.6934 0.2883 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8693 -1.6477 1.0551 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2344 0.5830 0.0185 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3051 0.4974 -0.0014 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0340 1.2767 1.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2372 2.2690 0.1929 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0126 -1.2435 0.2808 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3495 -3.0607 -0.0688 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9707 -2.5123 -0.3606 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2975 1.5471 -1.7066 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1551 2.0453 -1.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5827 1.9740 -0.8058 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6294 -0.9345 0.8990 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2352 -1.8924 2.5371 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8555 1.6129 0.0344 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 1 0 8 9 2 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 19 20 2 0 7 21 2 0 21 3 1 0 19 8 1 0 18 11 1 0 1 22 1 0 1 23 1 0 1 24 1 0 4 25 1 0 5 26 1 0 6 27 1 0 9 28 1 0 12 29 1 0 14 30 1 0 15 31 1 0 17 32 1 0 21 33 1 0 M END

Standard InCHIKey	VOCQAKWBOKDJIA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O5/c1-20-11-4-2-3-9(5-11)12-8-21-14-7-10(17)6-13(18)15(14)16(12)19/h2-8,17-18H,1H3
SMILES	COC1=CC=CC(C2=COC3=CC(O)=CC(O)=C3C2=O)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	284.07	Volume:	282.482 ? Van der Waals volume.
Dense:	1.006	LogP:	2.36 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.591 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.438 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	79.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.756	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.237	Fsp³:	0.062
MCE-18:	17.0 ? 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:	0.379	Fluc inhibitor:	0.968 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.777 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.623 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.517	Promiscuous compounds:	0.864

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.973	MDCK Permeability:	-4.835
Pgp-inhibitor:	0.316	Pgp-substrate:	0.423
PAMPA:	0.063 ? 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):	0.007
20% Bioavailability (F20%):	0.207	30% Bioavailability (F30%):	0.738
50% Bioavailability (F50%):	0.971

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.429
Plasma Protein Binding (PPB):	97.835%	Volume Distribution (VD):	-0.113
Fu:	1.625% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.834
OATP1B3 inhibitor:	0.957	BCRP inhibitor:	0.993
BSEP inhibitor:	0.945

ADMET: Metabolism

CYP1A2-inhibitor:	0.946	CYP1A2-substrate:	0.984
CYP2C19-inhibitor:	0.043	CYP2C19-substrate:	0.646
CYP2C9-inhibitor:	0.95	CYP2C9-substrate:	0.849
CYP2D6-inhibitor:	0.999	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.228
CYP2B6-substrate:	0.005	CYP2C8-inhibitor:	0.992
HLM stability:	0.967 ? 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):

5.712

Half-life (T1/2):

0.869

ADMET: Toxicity

hERG Blockers:	0.192	hERG Blockers (10um):	0.557
Human Hepatotoxicity (H-HT):	0.506	Drug-induced Liver Injury (DILI):	0.885
AMES Toxicity:	0.68	Rat Oral Acute Toxicity:	0.551
Maximum Recommended Daily Dose:	0.811	Skin Sensitization:	0.328
Carcinogencity:	0.77	Eye Corrosion:	0.055
Eye Irritation:	0.987	Respiratory Toxicity:	0.834
Drug-induced Neurotoxicity:	0.306	Ototoxicity:	0.196
Hematotoxicity:	0.135	Drug-induced Nephrotoxicity:	0.244
Genotoxicity:	0.929	RPMI-8226 Immunitoxicity:	0.081
A549 Cytotoxicity:	0.267	Hek293 Cytotoxicity:	0.578
BCF:	1.178 ? 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:	3.917 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.659 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.202 ? 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
NPO22402	Lupinus mutabilis	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22402	Lupinus mutabilis	Species	Fabaceae	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

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 NPC590405 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	26415
0.1-0.2	20142
0.2-0.3	2464
0.3-0.4	620
0.4-0.5	151
0.5-0.6	37
0.6-0.7	17
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
0.7857	Intermediate Similarity	NPC200316
0.7818	Intermediate Similarity	NPC294409
0.7818	Intermediate Similarity	NPC490701
0.7321	Intermediate Similarity	NPC78341
0.7288	Intermediate Similarity	NPC254702
0.7119	Intermediate Similarity	NPC194653
0.7037	Intermediate Similarity	NPC608554
0.6885	Remote Similarity	NPC104728
0.6833	Remote Similarity	NPC279668
0.6833	Remote Similarity	NPC278323
0.6833	Remote Similarity	NPC481044
0.678	Remote Similarity	NPC239363
0.6769	Remote Similarity	NPC479305
0.65	Remote Similarity	NPC19980
0.6452	Remote Similarity	NPC142876
0.6452	Remote Similarity	NPC264550
0.6429	Remote Similarity	NPC39426
0.6393	Remote Similarity	NPC309154
0.6364	Remote Similarity	NPC233918
0.625	Remote Similarity	NPC193792
0.6207	Remote Similarity	NPC38065
0.619	Remote Similarity	NPC483637
0.6119	Remote Similarity	NPC268059
0.6	Remote Similarity	NPC167595
0.5942	Remote Similarity	NPC474052
0.5938	Remote Similarity	NPC45291
0.5797	Remote Similarity	NPC128774
0.5667	Remote Similarity	NPC87545
0.5645	Remote Similarity	NPC116632
0.5645	Remote Similarity	NPC35763
0.5634	Remote Similarity	NPC482075
0.5634	Remote Similarity	NPC107838
0.5571	Remote Similarity	NPC280937
0.5556	Remote Similarity	NPC303644
0.5467	Remote Similarity	NPC156457
0.5455	Remote Similarity	NPC114192
0.5397	Remote Similarity	NPC131266
0.5397	Remote Similarity	NPC269451
0.5385	Remote Similarity	NPC12377
0.5362	Remote Similarity	NPC213659
0.5362	Remote Similarity	NPC326109
0.5312	Remote Similarity	NPC209560
0.5312	Remote Similarity	NPC490700
0.5312	Remote Similarity	NPC609386
0.5278	Remote Similarity	NPC488570
0.5256	Remote Similarity	NPC481043
0.5231	Remote Similarity	NPC209487
0.5217	Remote Similarity	NPC238279
0.5217	Remote Similarity	NPC608523
0.5211	Remote Similarity	NPC475705
0.5205	Remote Similarity	NPC231763
0.5205	Remote Similarity	NPC74178
0.5156	Remote Similarity	NPC59951
0.5135	Remote Similarity	NPC52889
0.5077	Remote Similarity	NPC245382
0.5075	Remote Similarity	NPC139364
0.5075	Remote Similarity	NPC191741
0.5075	Remote Similarity	NPC90665
0.507	Remote Similarity	NPC249824
0.507	Remote Similarity	NPC133400
0.507	Remote Similarity	NPC606200

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC590405 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4222
0.1-0.2	4799
0.2-0.3	121
0.3-0.4	6
0.4-0.5	1
0.5-0.6	0
0.6-0.7	1
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
0.6429	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