NPASS Compound

Natural Product: NPC586791

Natural Product ID	NPC586791
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	19725-42-9
IUPAC Name	3-(2-hydroxy-4-methoxy-phenyl)-7-methoxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0002506] Isoflavonoids [CHEMONTID:0002586] O-methylated isoflavonoids [CHEMONTID:0002602] 7-O-methylated isoflavonoids [CHEMONTID:0002689] 7-O-methylisoflavones

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 36 38 0 0 0 0 0 0 0 0999 V2000 -6.6926 0.3100 0.7525 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9054 0.7847 -0.3251 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5483 0.4791 -0.3234 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7496 0.9241 -1.3559 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3995 0.6429 -1.3920 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7945 -0.0949 -0.3963 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3654 -0.3711 -0.4700 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1327 -1.4926 -1.1013 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4144 -1.7221 -1.1568 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2841 -0.9061 -0.6205 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6151 -1.1657 -0.6907 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5573 -0.3010 -0.1211 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8719 -0.6630 -0.2528 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9792 0.0342 0.2281 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1178 0.8395 0.5250 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7841 1.1173 0.6058 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8685 0.2345 0.0272 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5209 0.5126 0.1072 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0560 1.5291 0.6785 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5898 -0.5409 0.6367 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9761 -1.2852 1.6401 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9564 -0.2600 0.6795 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4720 -0.7797 0.8489 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4970 0.8694 1.6680 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7693 0.4705 0.4779 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2208 1.5020 -2.1370 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7836 1.0074 -2.2238 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5223 -2.2141 -1.5683 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9301 -2.0667 -1.2031 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2266 -0.3999 1.2404 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8110 1.1204 0.3726 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8921 -0.1233 -0.3990 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8898 1.4806 0.9519 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4193 1.9880 1.0972 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5813 -0.8312 2.4771 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5471 -0.6289 1.5090 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 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 6 20 1 0 20 21 1 0 20 22 2 0 22 3 1 0 18 7 1 0 17 10 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 5 27 1 0 8 28 1 0 11 29 1 0 14 30 1 0 14 31 1 0 14 32 1 0 15 33 1 0 16 34 1 0 21 35 1 0 22 36 1 0 M END

Standard InCHIKey	ZQOPJNNVXTYJMC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O5/c1-20-10-3-5-12(15(18)7-10)14-9-22-16-8-11(21-2)4-6-13(16)17(14)19/h3-9,18H,1-2H3
SMILES	COC1=CC=C(C2=COC3=CC(OC)=CC=C3C2=O)C(O)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	298.08	Volume:	299.778 ? Van der Waals volume.
Dense:	0.994	LogP:	2.576 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.78 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.758 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	68.9 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.804	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.125	Fsp³:	0.118
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:	0.382	Fluc inhibitor:	0.998 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.919 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.495 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.464	Promiscuous compounds:	0.717

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.86	MDCK Permeability:	-4.711
Pgp-inhibitor:	0.555	Pgp-substrate:	0.016
PAMPA:	0.054 ? 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):	0.311
20% Bioavailability (F20%):	0.223	30% Bioavailability (F30%):	0.498
50% Bioavailability (F50%):	0.919

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.66
Plasma Protein Binding (PPB):	83.41%	Volume Distribution (VD):	-0.068
Fu:	15.6% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.991
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.947
BSEP inhibitor:	0.894

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.988
CYP2C19-inhibitor:	0.895	CYP2C19-substrate:	0.396
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.971
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.708
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.26
CYP2B6-substrate:	0.968	CYP2C8-inhibitor:	0.99
HLM stability:	0.847 ? 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):

4.744

Half-life (T1/2):

1.105

ADMET: Toxicity

hERG Blockers:	0.216	hERG Blockers (10um):	0.534
Human Hepatotoxicity (H-HT):	0.448	Drug-induced Liver Injury (DILI):	0.806
AMES Toxicity:	0.689	Rat Oral Acute Toxicity:	0.458
Maximum Recommended Daily Dose:	0.66	Skin Sensitization:	0.156
Carcinogencity:	0.802	Eye Corrosion:	0.106
Eye Irritation:	0.971	Respiratory Toxicity:	0.882
Drug-induced Neurotoxicity:	0.462	Ototoxicity:	0.244
Hematotoxicity:	0.264	Drug-induced Nephrotoxicity:	0.479
Genotoxicity:	0.528	RPMI-8226 Immunitoxicity:	0.149
A549 Cytotoxicity:	0.241	Hek293 Cytotoxicity:	0.457
BCF:	1.114 ? 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:	3.863 ? 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:	4.261 ? 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
NPO15668	Pycnanthus angolensis	Species	Myristicaceae	Eukaryota	roots	n.a.	n.a.	PMID[20055477]
NPO15668	Pycnanthus angolensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21495101]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15668	Pycnanthus angolensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO2788	Virola surinamensis	Species	Myristicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15668	Pycnanthus angolensis	Species	Myristicaceae	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 NPC586791 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	28590
0.1-0.2	18051
0.2-0.3	2613
0.3-0.4	452
0.4-0.5	120
0.5-0.6	23
0.6-0.7	5
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
0.75	Intermediate Similarity	NPC12175
0.7193	Intermediate Similarity	NPC100263
0.6981	Remote Similarity	NPC182428
0.6964	Remote Similarity	NPC181124
0.6333	Remote Similarity	NPC279668
0.6316	Remote Similarity	NPC185607
0.6102	Remote Similarity	NPC136095
0.5932	Remote Similarity	NPC216314
0.5932	Remote Similarity	NPC603503
0.5806	Remote Similarity	NPC602183
0.5625	Remote Similarity	NPC254741
0.5574	Remote Similarity	NPC209560
0.5574	Remote Similarity	NPC490700
0.5556	Remote Similarity	NPC195763
0.5556	Remote Similarity	NPC90665
0.5484	Remote Similarity	NPC471590
0.5469	Remote Similarity	NPC153008
0.541	Remote Similarity	NPC10467
0.541	Remote Similarity	NPC116632
0.541	Remote Similarity	NPC479067
0.5385	Remote Similarity	NPC478213
0.5323	Remote Similarity	NPC121522
0.5312	Remote Similarity	NPC156953
0.5254	Remote Similarity	NPC120924
0.5231	Remote Similarity	NPC55162
0.5231	Remote Similarity	NPC291802
0.5161	Remote Similarity	NPC333691
0.5147	Remote Similarity	NPC185401
0.5077	Remote Similarity	NPC40290
0.5065	Remote Similarity	NPC479402

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC586791 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5020
0.1-0.2	4018
0.2-0.3	107
0.3-0.4	3
0.4-0.5	1
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
0.541	Remote Similarity	NPD2796	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