NPASS Compound

Natural Product: NPC530060

Natural Product ID	NPC530060
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7,8,3',4'-Pentahydroxy-6-methoxyflavone
IUPAC Name	2-(3,4-dihydroxyphenyl)-5,7,8-trihydroxy-6-methoxy-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 36 38 0 0 0 0 0 0 0 0999 V2000 -5.7954 0.5637 1.0876 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0631 -0.1011 0.0770 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6829 -0.2064 0.0866 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0781 -1.2810 0.7041 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8553 -2.2709 1.3244 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7009 -1.3608 0.6987 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1244 -2.4587 1.3312 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9333 -0.3884 0.0893 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3718 -0.4722 0.0890 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1608 0.4173 -0.4718 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5953 0.2297 -0.4152 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5127 1.0968 -0.9676 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8878 0.8890 -0.8966 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3767 -0.2244 -0.2514 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7517 -0.3876 -0.2071 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4949 -1.1151 0.3136 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0258 -2.2260 0.9557 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1398 -0.8872 0.2299 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6143 1.5062 -1.1001 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7721 1.6244 -1.1172 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2757 2.6211 -1.6922 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5771 0.6761 -0.5207 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9525 0.7824 -0.5312 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5677 1.8805 -1.1623 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0734 -0.1491 1.9119 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1213 1.3014 1.5515 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7369 0.9947 0.7025 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8405 -2.3308 1.1020 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5909 -3.3489 1.2526 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2005 1.9736 -1.4784 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5748 1.6039 -1.3494 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3468 0.4418 -0.1309 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5021 -2.0391 1.8387 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4789 -1.6062 0.6842 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2113 2.2607 -1.5730 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5044 1.9905 -2.1653 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 4 6 1 0 6 7 1 0 6 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 1 0 16 18 2 0 10 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 22 23 2 0 23 24 1 0 23 3 1 0 22 8 1 0 18 11 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 0 7 29 1 0 12 30 1 0 13 31 1 0 15 32 1 0 17 33 1 0 18 34 1 0 19 35 1 0 24 36 1 0 M END

Standard InCHIKey	BCQKWILTFJFWRE-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O8/c1-23-16-12(20)11-9(19)5-10(24-15(11)13(21)14(16)22)6-2-3-7(17)8(18)4-6/h2-5,17-18,20-22H,1H3
SMILES	COC1=C(O)C(O)=C2OC(C3=CC=C(O)C(O)=C3)=CC(=O)C2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.05	Volume:	308.853 ? Van der Waals volume.
Dense:	1.075	LogP:	1.743 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.768 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.972 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	140.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	5.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.354	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.729	Fsp³:	0.062
MCE-18:	20.0 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.856	Fluc inhibitor:	0.508 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.874 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.445 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.566	Promiscuous compounds:	0.941

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.2	MDCK Permeability:	-4.794
Pgp-inhibitor:	0.012	Pgp-substrate:	0.018
PAMPA:	0.481 ? 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):	0.077
20% Bioavailability (F20%):	0.884	30% Bioavailability (F30%):	0.975
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.963
Plasma Protein Binding (PPB):	96.155%	Volume Distribution (VD):	-0.391
Fu:	4.487% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.962
OATP1B3 inhibitor:	0.994	BCRP inhibitor:	0.88
BSEP inhibitor:	0.044

ADMET: Metabolism

CYP1A2-inhibitor:	0.086	CYP1A2-substrate:	0.029
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.002
CYP2C9-inhibitor:	0.286	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.943	CYP2D6-substrate:	0.963
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.524
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.966
HLM stability:	0.494 ? 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):

11.653

Half-life (T1/2):

1.823

ADMET: Toxicity

hERG Blockers:	0.064	hERG Blockers (10um):	0.552
Human Hepatotoxicity (H-HT):	0.378	Drug-induced Liver Injury (DILI):	0.849
AMES Toxicity:	0.55	Rat Oral Acute Toxicity:	0.389
Maximum Recommended Daily Dose:	0.566	Skin Sensitization:	0.972
Carcinogencity:	0.5	Eye Corrosion:	0.212
Eye Irritation:	0.99	Respiratory Toxicity:	0.417
Drug-induced Neurotoxicity:	0.01	Ototoxicity:	0.371
Hematotoxicity:	0.066	Drug-induced Nephrotoxicity:	0.022
Genotoxicity:	0.818	RPMI-8226 Immunitoxicity:	0.017
A549 Cytotoxicity:	0.723	Hek293 Cytotoxicity:	0.297
BCF:	0.974 ? 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:	3.654 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.542 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.237 ? 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
NPO27694	Hemizonia fasciculata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO49823	Hemizonia increscens villosa	Genus	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26875	Hemizonia lobbii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO42203	Hemizonia pentactis	Genus	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27694	Hemizonia fasciculata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26875	Hemizonia lobbii	Species	Asteraceae	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 NPC530060 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	30813
0.1-0.2	16027
0.2-0.3	2249
0.3-0.4	566
0.4-0.5	158
0.5-0.6	35
0.6-0.7	7
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
0.6852	Remote Similarity	NPC100887
0.6667	Remote Similarity	NPC17286
0.6429	Remote Similarity	NPC201136
0.6429	Remote Similarity	NPC25270
0.6429	Remote Similarity	NPC162313
0.625	Remote Similarity	NPC188203
0.614	Remote Similarity	NPC108406
0.5893	Remote Similarity	NPC607196
0.5789	Remote Similarity	NPC138360
0.5636	Remote Similarity	NPC296197
0.5593	Remote Similarity	NPC256283
0.5593	Remote Similarity	NPC604569
0.5593	Remote Similarity	NPC605047
0.5517	Remote Similarity	NPC241498
0.5517	Remote Similarity	NPC287979
0.5517	Remote Similarity	NPC275836
0.55	Remote Similarity	NPC280339
0.55	Remote Similarity	NPC146165
0.5424	Remote Similarity	NPC604462
0.5357	Remote Similarity	NPC275772
0.5273	Remote Similarity	NPC216318
0.5263	Remote Similarity	NPC279121
0.5254	Remote Similarity	NPC71334
0.5254	Remote Similarity	NPC98661
0.5246	Remote Similarity	NPC212678
0.5246	Remote Similarity	NPC83508
0.5238	Remote Similarity	NPC258331
0.5179	Remote Similarity	NPC259713
0.5167	Remote Similarity	NPC198826
0.5167	Remote Similarity	NPC130894
0.5167	Remote Similarity	NPC231018
0.5167	Remote Similarity	NPC120163
0.5167	Remote Similarity	NPC163524
0.5161	Remote Similarity	NPC4455
0.5161	Remote Similarity	NPC160951
0.5161	Remote Similarity	NPC196439
0.5085	Remote Similarity	NPC293183
0.5085	Remote Similarity	NPC602963
0.5085	Remote Similarity	NPC606920
0.5082	Remote Similarity	NPC159275
0.5082	Remote Similarity	NPC163780
0.5082	Remote Similarity	NPC78913

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC530060 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5764
0.1-0.2	3322
0.2-0.3	57
0.3-0.4	5
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
0.5263	Remote Similarity	NPD1511	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