NPASS Compound

Natural Product: NPC530263

Natural Product ID	NPC530263
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5,7,4'-Trihydroxy-2',3',5'-trimethoxyflavone
IUPAC Name	5,7-dihydroxy-2-(4-hydroxy-2,3,5-trimethoxy-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 42 44 0 0 0 0 0 0 0 0999 V2000 -3.6141 -3.4979 -0.5572 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0763 -2.1938 -0.8189 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2006 -1.1387 -0.7542 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8690 -1.4104 -0.4265 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9323 -0.4200 -0.3404 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4812 -0.6630 -0.0029 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9132 -1.9382 0.2639 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2533 -2.1529 0.5817 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6669 -3.3177 0.8295 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0746 -1.0527 0.6088 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4047 -1.2544 0.9227 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8184 -2.5445 1.1876 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2875 -0.1757 0.9659 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7927 1.0816 0.6880 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6985 2.1419 0.7387 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4630 1.2849 0.3740 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5706 0.2080 0.3285 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3155 0.3734 0.0356 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3376 0.9002 -0.5912 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4094 1.9123 -0.5093 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1854 2.5818 0.7135 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6398 1.2119 -0.9175 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0997 2.4952 -1.1760 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6249 3.2329 -0.0902 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5312 0.1620 -0.9865 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8536 0.4409 -1.3133 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5053 -4.1632 -0.5812 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1116 -3.6015 0.4214 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8724 -3.7594 -1.3344 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5672 -2.4411 -0.2340 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2541 -2.8098 0.2410 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1591 -3.2016 0.5225 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3195 -0.3767 1.2155 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6916 2.8238 -0.0117 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1055 2.2840 0.1607 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8684 2.9897 0.6594 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9161 3.3987 0.8288 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3211 1.9247 1.6019 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7494 3.1305 -0.0496 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3805 4.2964 -0.2338 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2546 2.8629 0.8950 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0862 0.3754 -2.3077 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 1 0 6 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 2 0 14 15 1 0 14 16 1 0 16 17 2 0 17 18 1 0 5 19 2 0 19 20 1 0 20 21 1 0 19 22 1 0 22 23 1 0 23 24 1 0 22 25 2 0 25 26 1 0 25 3 1 0 18 6 1 0 17 10 1 0 1 27 1 0 1 28 1 0 1 29 1 0 4 30 1 0 7 31 1 0 12 32 1 0 13 33 1 0 15 34 1 0 16 35 1 0 21 36 1 0 21 37 1 0 21 38 1 0 24 39 1 0 24 40 1 0 24 41 1 0 26 42 1 0 M END

Standard InCHIKey	KHVJWEFGGGAAEH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H16O8/c1-23-14-6-9(17(24-2)18(25-3)16(14)22)12-7-11(21)15-10(20)4-8(19)5-13(15)26-12/h4-7,19-20,22H,1-3H3
SMILES	COC1=CC(C2=CC(=O)C3=C(O)C=C(O)C=C3O2)=C(OC)C(OC)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	360.08	Volume:	343.445 ? Van der Waals volume.
Dense:	1.048	LogP:	2.045 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.962 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.168 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	18.0
TPSA:	118.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.65	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.641	Fsp³:	0.167
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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.328	Fluc inhibitor:	0.289 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.847 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.571 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.388	Promiscuous compounds:	0.914

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.232	MDCK Permeability:	-4.825
Pgp-inhibitor:	0.114	Pgp-substrate:	0.447
PAMPA:	0.043 ? 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):	0.006
20% Bioavailability (F20%):	0.092	30% Bioavailability (F30%):	0.46
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.064	MRP1:	0.951
Plasma Protein Binding (PPB):	96.639%	Volume Distribution (VD):	-0.489
Fu:	2.988% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.96
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.993
BSEP inhibitor:	0.638

ADMET: Metabolism

CYP1A2-inhibitor:	0.999	CYP1A2-substrate:	0.033
CYP2C19-inhibitor:	0.042	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.557	CYP2C9-substrate:	0.947
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.923
CYP3A4-inhibitor:	0.02	CYP3A4-substrate:	0.009
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.866
HLM stability:	0.71 ? 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):

3.59

Half-life (T1/2):

1.42

ADMET: Toxicity

hERG Blockers:	0.079	hERG Blockers (10um):	0.53
Human Hepatotoxicity (H-HT):	0.402	Drug-induced Liver Injury (DILI):	0.72
AMES Toxicity:	0.491	Rat Oral Acute Toxicity:	0.458
Maximum Recommended Daily Dose:	0.728	Skin Sensitization:	0.65
Carcinogencity:	0.757	Eye Corrosion:	0.502
Eye Irritation:	0.993	Respiratory Toxicity:	0.827
Drug-induced Neurotoxicity:	0.107	Ototoxicity:	0.102
Hematotoxicity:	0.138	Drug-induced Nephrotoxicity:	0.048
Genotoxicity:	0.738	RPMI-8226 Immunitoxicity:	0.105
A549 Cytotoxicity:	0.293	Hek293 Cytotoxicity:	0.704
BCF:	0.981 ? 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:	3.574 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.347 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.741 ? 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
NPO25700	Psiadia punctulata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25700	Psiadia punctulata	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 NPC530263 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	31195
0.1-0.2	15687
0.2-0.3	2074
0.3-0.4	694
0.4-0.5	166
0.5-0.6	26
0.6-0.7	8
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
0.7593	Intermediate Similarity	NPC120464
0.7455	Intermediate Similarity	NPC600900
0.6667	Remote Similarity	NPC62536
0.6667	Remote Similarity	NPC483773
0.661	Remote Similarity	NPC606638
0.65	Remote Similarity	NPC183950
0.6379	Remote Similarity	NPC231772
0.6379	Remote Similarity	NPC601901
0.6333	Remote Similarity	NPC52005
0.6333	Remote Similarity	NPC12200
0.5833	Remote Similarity	NPC28274
0.569	Remote Similarity	NPC274121
0.5614	Remote Similarity	NPC50898
0.5614	Remote Similarity	NPC78540
0.5593	Remote Similarity	NPC213216
0.5588	Remote Similarity	NPC183
0.5538	Remote Similarity	NPC605634
0.5517	Remote Similarity	NPC175013
0.55	Remote Similarity	NPC610974
0.5424	Remote Similarity	NPC279121
0.541	Remote Similarity	NPC284552
0.541	Remote Similarity	NPC605617
0.5385	Remote Similarity	NPC483775
0.5323	Remote Similarity	NPC48479
0.5231	Remote Similarity	NPC133953
0.5161	Remote Similarity	NPC219330
0.5135	Remote Similarity	NPC63454
0.5135	Remote Similarity	NPC183851
0.5128	Remote Similarity	NPC101731
0.5079	Remote Similarity	NPC276409
0.5079	Remote Similarity	NPC610359
0.5077	Remote Similarity	NPC162351
0.5077	Remote Similarity	NPC609179
0.5068	Remote Similarity	NPC150908
0.5068	Remote Similarity	NPC600972
0.5063	Remote Similarity	NPC165970

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC530263 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6249
0.1-0.2	2848
0.2-0.3	46
0.3-0.4	4
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
0.5424	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