NPASS Compound

Natural Product: NPC591261

Natural Product ID	NPC591261
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	8-Hydroxyquercetagetin
IUPAC Name	2-(3,4-dihydroxyphenyl)-3,5,6,7,8-pentahydroxy-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 -1.7782 -2.8255 -1.2830 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3292 -1.7551 -0.7981 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0550 -1.5314 -0.7135 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8859 -2.5130 -1.1744 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5555 -0.3835 -0.1937 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9376 -0.0058 -0.0385 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2729 1.2064 0.5129 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5832 1.6337 0.6919 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5811 0.7764 0.2857 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9250 1.1623 0.4452 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3095 -0.4461 -0.2713 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3119 -1.3104 -0.6806 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9632 -0.8133 -0.4221 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3411 0.5157 0.2303 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6151 0.3956 0.1918 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4058 1.4316 0.6772 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8474 2.5990 1.2052 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7721 1.2877 0.6290 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5949 2.3025 1.1051 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3194 0.1356 0.1079 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7070 0.0095 0.0682 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5115 -0.8977 -0.3764 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0487 -2.0632 -0.9039 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1514 -0.7545 -0.3285 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0333 -3.3513 -0.6008 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4932 1.8904 0.8367 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8240 2.5850 1.1249 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6067 0.8055 -0.2255 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8495 -1.1200 -1.5231 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8392 -1.7893 -0.8681 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0383 2.9730 0.7123 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0347 2.1560 2.0204 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2673 0.4925 -0.6463 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2647 -2.7985 -0.2192 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 3 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 9 11 1 0 11 12 1 0 11 13 2 0 5 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 1 0 18 20 2 0 20 21 1 0 20 22 1 0 22 23 1 0 22 24 2 0 24 2 1 0 13 6 1 0 24 15 1 0 4 25 1 0 7 26 1 0 8 27 1 0 10 28 1 0 12 29 1 0 13 30 1 0 17 31 1 0 19 32 1 0 21 33 1 0 23 34 1 0 M END

Standard InCHIKey	IVVIBMKOLWEERH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H10O9/c16-5-2-1-4(3-6(5)17)14-12(22)9(19)7-8(18)10(20)11(21)13(23)15(7)24-14/h1-3,16-18,20-23H
SMILES	O=C1C(O)=C(C2=CC=C(O)C(O)=C2)OC2=C(O)C(O)=C(O)C(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	334.03	Volume:	300.347 ? Van der Waals volume.
Dense:	1.112	LogP:	1.102 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.987 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.345 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	171.82 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	7.0	Rings:	3.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.256	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.871	Fsp³:	0.0
MCE-18:	21.0 ? 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:	0.893	Fluc inhibitor:	0.333 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.674 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.154 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.719	Promiscuous compounds:	0.944

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.866	MDCK Permeability:	-4.96
Pgp-inhibitor:	0.005	Pgp-substrate:	0.002
PAMPA:	0.944 ? 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):	0.324
20% Bioavailability (F20%):	0.908	30% Bioavailability (F30%):	0.996
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.968
Plasma Protein Binding (PPB):	96.681%	Volume Distribution (VD):	-0.612
Fu:	3.867% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.972
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.975
BSEP inhibitor:	0.036

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.005
CYP2C9-inhibitor:	0.026	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.43	CYP2D6-substrate:	0.685
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.649
HLM stability:	0.636 ? 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):

14.137

Half-life (T1/2):

2.197

ADMET: Toxicity

hERG Blockers:	0.035	hERG Blockers (10um):	0.559
Human Hepatotoxicity (H-HT):	0.379	Drug-induced Liver Injury (DILI):	0.887
AMES Toxicity:	0.55	Rat Oral Acute Toxicity:	0.312
Maximum Recommended Daily Dose:	0.455	Skin Sensitization:	0.993
Carcinogencity:	0.266	Eye Corrosion:	0.062
Eye Irritation:	0.989	Respiratory Toxicity:	0.231
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.619
Hematotoxicity:	0.028	Drug-induced Nephrotoxicity:	0.011
Genotoxicity:	0.918	RPMI-8226 Immunitoxicity:	0.007
A549 Cytotoxicity:	0.899	Hek293 Cytotoxicity:	0.171
BCF:	0.947 ? 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:	3.46 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.421 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.112 ? 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
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39181940]
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39716808]
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50904	African marigold	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO17962	Tagetes erecta	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO17962	Tagetes erecta	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 NPC591261 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	37472
0.1-0.2	10456
0.2-0.3	1572
0.3-0.4	287
0.4-0.5	51
0.5-0.6	13
0.6-0.7	3
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
0.7391	Intermediate Similarity	NPC27208
0.7021	Intermediate Similarity	NPC77858
0.6531	Remote Similarity	NPC225731
0.6458	Remote Similarity	NPC606557
0.6111	Remote Similarity	NPC32420
0.5882	Remote Similarity	NPC195351
0.5882	Remote Similarity	NPC20791
0.5769	Remote Similarity	NPC179271
0.5636	Remote Similarity	NPC87125
0.5536	Remote Similarity	NPC480465
0.549	Remote Similarity	NPC216318
0.5455	Remote Similarity	NPC98661
0.5385	Remote Similarity	NPC51443
0.5283	Remote Similarity	NPC275772
0.5283	Remote Similarity	NPC169749
0.5094	Remote Similarity	NPC17286
0.5088	Remote Similarity	NPC270465
0.5088	Remote Similarity	NPC605755

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC591261 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7565
0.1-0.2	1559
0.2-0.3	23
0.3-0.4	1
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
0.5882	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