NPASS Compound

Natural Product: NPC526742

Natural Product ID	NPC526742
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7,2'-Trihydroxy-6'-methoxyflavone
IUPAC Name	5,7-dihydroxy-2-(2-hydroxy-6-methoxy-phenyl)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 34 36 0 0 0 0 0 0 0 0999 V2000 -3.9927 0.6799 -2.1367 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8330 0.4768 -1.3908 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7969 0.3353 -0.0181 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9925 0.3942 0.7168 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9837 0.2557 2.0904 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7949 0.0570 2.7590 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6451 0.0040 2.0160 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4238 -0.1988 2.6905 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6231 0.1409 0.6248 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2999 0.0579 -0.0115 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0592 0.1655 -1.3545 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2375 0.0755 -1.8917 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4401 0.1756 -3.1178 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3027 -0.1269 -1.0468 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5912 -0.2213 -1.5300 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8523 -0.1123 -2.9106 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6290 -0.4238 -0.6537 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3416 -0.5265 0.6920 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3598 -0.7308 1.6080 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0457 -0.4303 1.1659 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9916 -0.2267 0.2965 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7689 -0.1358 0.7425 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7062 -0.1655 -1.9714 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7383 0.6892 -3.2159 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5144 1.6242 -1.9012 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8915 0.5484 0.1721 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8777 0.2959 2.6787 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7435 -0.0559 3.8305 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1856 -1.0913 3.0865 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8567 0.3225 -2.0422 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0939 0.7760 -3.3359 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6440 -0.5019 -0.9974 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8330 -1.6150 1.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8272 -0.5116 2.2215 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 7 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 9 3 1 0 22 10 1 0 21 14 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 5 27 1 0 6 28 1 0 8 29 1 0 11 30 1 0 16 31 1 0 17 32 1 0 19 33 1 0 20 34 1 0 M END

Standard InCHIKey	DXCJDOXICXPVHQ-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O6/c1-21-12-4-2-3-9(18)16(12)14-7-11(20)15-10(19)5-8(17)6-13(15)22-14/h2-7,17-19H,1H3
SMILES	COC1=CC=CC(O)=C1C1=CC(=O)C2=C(O)C=C(O)C=C2O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	300.06	Volume:	291.273 ? Van der Waals volume.
Dense:	1.03	LogP:	2.211 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.352 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.856 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	100.13 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.672	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.47	Fsp³:	0.062
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:	0.508	Fluc inhibitor:	0.626 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.789 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.559 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.492	Promiscuous compounds:	0.933

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.954	MDCK Permeability:	-4.798
Pgp-inhibitor:	0.052	Pgp-substrate:	0.608
PAMPA:	0.126 ? 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):	0.009
20% Bioavailability (F20%):	0.202	30% Bioavailability (F30%):	0.711
50% Bioavailability (F50%):	0.973

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.225	MRP1:	0.784
Plasma Protein Binding (PPB):	95.935%	Volume Distribution (VD):	-0.282
Fu:	4.879% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.83
OATP1B3 inhibitor:	0.941	BCRP inhibitor:	0.856
BSEP inhibitor:	0.494

ADMET: Metabolism

CYP1A2-inhibitor:	0.997	CYP1A2-substrate:	0.737
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.015
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.988
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.994
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.247
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.749
HLM stability:	0.381 ? 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):

3.466

Half-life (T1/2):

1.119

ADMET: Toxicity

hERG Blockers:	0.075	hERG Blockers (10um):	0.519
Human Hepatotoxicity (H-HT):	0.457	Drug-induced Liver Injury (DILI):	0.661
AMES Toxicity:	0.678	Rat Oral Acute Toxicity:	0.499
Maximum Recommended Daily Dose:	0.778	Skin Sensitization:	0.652
Carcinogencity:	0.77	Eye Corrosion:	0.287
Eye Irritation:	0.996	Respiratory Toxicity:	0.841
Drug-induced Neurotoxicity:	0.07	Ototoxicity:	0.094
Hematotoxicity:	0.085	Drug-induced Nephrotoxicity:	0.061
Genotoxicity:	0.927	RPMI-8226 Immunitoxicity:	0.091
A549 Cytotoxicity:	0.313	Hek293 Cytotoxicity:	0.726
BCF:	1.243 ? 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:	3.723 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.497 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.903 ? 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]
NPO28877	Scutellaria baicalensis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
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]
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]
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 NPC526742 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	26730
0.1-0.2	19526
0.2-0.3	2576
0.3-0.4	809
0.4-0.5	171
0.5-0.6	33
0.6-0.7	12
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
0.6667	Remote Similarity	NPC231772
0.6429	Remote Similarity	NPC213216
0.6379	Remote Similarity	NPC62536
0.6379	Remote Similarity	NPC120464
0.6379	Remote Similarity	NPC483773
0.6379	Remote Similarity	NPC601901
0.6333	Remote Similarity	NPC92659
0.6333	Remote Similarity	NPC52005
0.6333	Remote Similarity	NPC12200
0.6271	Remote Similarity	NPC600900
0.623	Remote Similarity	NPC183950
0.6066	Remote Similarity	NPC606638
0.5965	Remote Similarity	NPC274121
0.5893	Remote Similarity	NPC50898
0.5893	Remote Similarity	NPC78540
0.5857	Remote Similarity	NPC71061
0.5857	Remote Similarity	NPC72425
0.5857	Remote Similarity	NPC303485
0.5763	Remote Similarity	NPC610974
0.5714	Remote Similarity	NPC150908
0.5714	Remote Similarity	NPC600972
0.569	Remote Similarity	NPC279121
0.5667	Remote Similarity	NPC605617
0.5634	Remote Similarity	NPC290830
0.5616	Remote Similarity	NPC601565
0.5588	Remote Similarity	NPC183
0.5538	Remote Similarity	NPC605634
0.5517	Remote Similarity	NPC175013
0.5479	Remote Similarity	NPC215203
0.5342	Remote Similarity	NPC272064
0.5342	Remote Similarity	NPC186227
0.5294	Remote Similarity	NPC112954
0.5238	Remote Similarity	NPC142540
0.5238	Remote Similarity	NPC604312
0.5161	Remote Similarity	NPC184536
0.5161	Remote Similarity	NPC103342
0.5147	Remote Similarity	NPC138299
0.5147	Remote Similarity	NPC111112
0.5135	Remote Similarity	NPC63454
0.5135	Remote Similarity	NPC183851
0.5079	Remote Similarity	NPC286342
0.5079	Remote Similarity	NPC59951
0.5079	Remote Similarity	NPC241838
0.5077	Remote Similarity	NPC124784
0.5072	Remote Similarity	NPC291746

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC526742 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4607
0.1-0.2	4460
0.2-0.3	75
0.3-0.4	5
0.4-0.5	2
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
0.569	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