NPASS Compound

Natural Product: NPC589691

Natural Product ID	NPC589691
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	82475-00-1
IUPAC Name	2-(2,6-dihydroxyphenyl)-5,7-dihydroxy-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 31 33 0 0 0 0 0 0 0 0999 V2000 2.0196 -2.0178 2.0974 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4388 -1.2500 1.2964 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0490 -1.2700 1.1203 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5937 -0.4313 0.2441 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0169 -0.3897 0.0056 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9669 -1.1727 0.6062 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6250 -2.1142 1.5366 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3353 -1.0708 0.3189 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7675 -0.1520 -0.6028 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8330 0.6558 -1.2289 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4960 0.5372 -0.9303 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6192 1.3814 -1.5985 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1770 0.3970 -0.4241 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4784 0.4735 -0.3133 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1631 1.3812 -1.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5158 1.4868 -0.9773 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2457 2.4196 -1.7492 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2026 0.6678 -0.1135 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5466 -0.2509 0.6556 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2092 -1.0965 1.5410 O 0 0 0 0 0 0 0 0 0 0 0 0 2.1669 -0.3475 0.5527 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4827 -1.9746 1.7061 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7423 -2.0260 2.5356 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0611 -1.6931 0.8004 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8161 -0.0491 -0.8463 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1510 1.3798 -1.9520 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5606 2.3383 -1.2284 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6497 2.0543 -1.7708 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3671 3.3659 -1.3791 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2706 0.7662 -0.0560 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5672 -1.9987 1.2218 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 6 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 4 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 16 18 2 0 18 19 1 0 19 20 1 0 19 21 2 0 21 2 1 0 11 5 1 0 21 14 1 0 3 22 1 0 7 23 1 0 8 24 1 0 9 25 1 0 10 26 1 0 12 27 1 0 15 28 1 0 17 29 1 0 18 30 1 0 20 31 1 0 M END

Standard InCHIKey	WJXXUIYFPVIHDH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O6/c16-7-4-10(19)15-11(20)6-13(21-12(15)5-7)14-8(17)2-1-3-9(14)18/h1-6,16-19H
SMILES	O=C1C=C(C2=C(O)C=CC=C2O)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	286.05	Volume:	273.977 ? Van der Waals volume.
Dense:	1.044	LogP:	2.25 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.322 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.932 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
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:	0.546	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.537	Fsp³:	0.0
MCE-18:	18.0 ? 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:	0.77	Fluc inhibitor:	0.81 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.749 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.347 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.715	Promiscuous compounds:	0.956

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.086	MDCK Permeability:	-4.771
Pgp-inhibitor:	0.023	Pgp-substrate:	0.449
PAMPA:	0.202 ? 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):	0.002
20% Bioavailability (F20%):	0.215	30% Bioavailability (F30%):	0.758
50% Bioavailability (F50%):	0.957

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.232	MRP1:	0.72
Plasma Protein Binding (PPB):	95.225%	Volume Distribution (VD):	-0.316
Fu:	6.861% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.764
OATP1B3 inhibitor:	0.833	BCRP inhibitor:	0.823
BSEP inhibitor:	0.473

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.532
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.084
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	0.996
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.009	CYP3A4-substrate:	0.986
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.998
HLM stability:	0.087 ? 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):

1.522

Half-life (T1/2):

1.547

ADMET: Toxicity

hERG Blockers:	0.044	hERG Blockers (10um):	0.477
Human Hepatotoxicity (H-HT):	0.452	Drug-induced Liver Injury (DILI):	0.467
AMES Toxicity:	0.657	Rat Oral Acute Toxicity:	0.507
Maximum Recommended Daily Dose:	0.796	Skin Sensitization:	0.655
Carcinogencity:	0.611	Eye Corrosion:	0.162
Eye Irritation:	0.996	Respiratory Toxicity:	0.873
Drug-induced Neurotoxicity:	0.063	Ototoxicity:	0.102
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.079
Genotoxicity:	0.956	RPMI-8226 Immunitoxicity:	0.103
A549 Cytotoxicity:	0.468	Hek293 Cytotoxicity:	0.76
BCF:	1.267 ? 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:	3.656 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.458 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.799 ? 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
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19829679]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	root	n.a.	PMID[21087019]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22314230]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23521110]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37569279]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9834167]
NPO53376	Scutellaria planifolia	Genus	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13167	Scutellaria amoena	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13167	Scutellaria amoena	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13167	Scutellaria amoena	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13167	Scutellaria amoena	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13167	Scutellaria amoena	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	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 NPC589691 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	37199
0.1-0.2	10483
0.2-0.3	1570
0.3-0.4	465
0.4-0.5	103
0.5-0.6	26
0.6-0.7	9
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	NPC213216
0.7083	Intermediate Similarity	NPC601197
0.6939	Remote Similarity	NPC274121
0.6875	Remote Similarity	NPC50898
0.6875	Remote Similarity	NPC78540
0.6667	Remote Similarity	NPC610974
0.66	Remote Similarity	NPC279121
0.64	Remote Similarity	NPC175013
0.6226	Remote Similarity	NPC605617
0.6111	Remote Similarity	NPC62536
0.6	Remote Similarity	NPC600900
0.5849	Remote Similarity	NPC256042
0.5818	Remote Similarity	NPC231772
0.5818	Remote Similarity	NPC120464
0.5818	Remote Similarity	NPC483773
0.5818	Remote Similarity	NPC601901
0.569	Remote Similarity	NPC183950
0.5574	Remote Similarity	NPC138299
0.5574	Remote Similarity	NPC111112
0.5517	Remote Similarity	NPC52005
0.5517	Remote Similarity	NPC12200
0.5517	Remote Similarity	NPC606638
0.5484	Remote Similarity	NPC112954
0.5484	Remote Similarity	NPC291746
0.537	Remote Similarity	NPC216361
0.5312	Remote Similarity	NPC254351
0.5283	Remote Similarity	NPC116775
0.5283	Remote Similarity	NPC187432
0.5246	Remote Similarity	NPC605634
0.5238	Remote Similarity	NPC301217
0.5231	Remote Similarity	NPC603692
0.5231	Remote Similarity	NPC610480
0.5185	Remote Similarity	NPC20791
0.5152	Remote Similarity	NPC259757
0.5091	Remote Similarity	NPC179271
0.5077	Remote Similarity	NPC34089
0.5077	Remote Similarity	NPC196179

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC589691 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7495
0.1-0.2	1611
0.2-0.3	37
0.3-0.4	4
0.4-0.5	1
0.5-0.6	1
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
0.66	Remote Similarity	NPD1511	Phase 2
0.5185	Remote Similarity	NPD1512	Phase 3

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