NPASS Compound

Natural Product: NPC503454

Natural Product ID	NPC503454
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Quercetagetin 7-methyl ether
IUPAC Name	2-(3,4-dihydroxyphenyl)-3,5,6-trihydroxy-7-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 -5.1920 -1.4140 -2.1530 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4082 -0.9821 -1.3400 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5240 -0.4949 -0.4229 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1856 -0.5845 -0.7132 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2079 -0.1232 0.1367 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5877 0.4550 1.3369 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9374 0.5447 1.6327 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2784 1.1239 2.8352 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9229 0.0817 0.7768 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2500 0.1880 1.0972 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6096 0.9141 2.1718 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8988 1.4431 3.2612 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7498 0.8093 1.8376 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6907 1.2942 2.7283 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0423 0.2236 0.6330 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4124 0.0518 0.1689 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6237 -0.6825 -0.9856 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8550 -0.8949 -1.5363 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9516 -0.3477 -0.9078 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2505 -0.5112 -1.3967 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8067 0.4065 0.2650 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9037 0.9492 0.8864 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5268 0.5731 0.7545 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0521 -0.2059 -0.1411 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2279 -2.5792 -2.2225 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0915 -1.1750 -3.2840 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3351 -1.2429 -1.9582 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8700 -1.0453 -1.6641 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2156 0.5261 3.6724 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7554 1.0735 1.1337 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6977 2.3113 2.9102 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7468 -1.1116 -1.4690 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9890 -1.4793 -2.4441 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9381 0.2265 -1.3089 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8045 0.5110 0.7023 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4566 1.1674 1.6509 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 6 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 2 0 15 24 1 0 9 3 1 0 23 16 1 0 24 5 1 0 1 25 1 0 1 26 1 0 1 27 1 0 4 28 1 0 8 29 1 0 10 30 1 0 14 31 1 0 17 32 1 0 18 33 1 0 20 34 1 0 22 35 1 0 23 36 1 0 M END

Standard InCHIKey	NJNWJNSULVNMQF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O8/c1-23-10-5-9-11(13(20)12(10)19)14(21)15(22)16(24-9)6-2-3-7(17)8(18)4-6/h2-5,17-20,22H,1H3
SMILES	COC1=CC2=C(C(O)=C1O)C(=O)C(O)=C(C1=CC=C(O)C(O)=C1)O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	332.05	Volume:	308.853 ? Van der Waals volume.
Dense:	1.075	LogP:	1.398 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.547 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.821 ? 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:	0.449	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.611	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:	0.862	Fluc inhibitor:	0.443 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.933 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.398 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.567	Promiscuous compounds:	0.92

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.529	MDCK Permeability:	-4.859
Pgp-inhibitor:	0.075	Pgp-substrate:	0.005
PAMPA:	0.535 ? 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):	0.536
20% Bioavailability (F20%):	0.605	30% Bioavailability (F30%):	0.983
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.925
Plasma Protein Binding (PPB):	97.508%	Volume Distribution (VD):	-0.66
Fu:	2.936% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.995
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.995
BSEP inhibitor:	0.14

ADMET: Metabolism

CYP1A2-inhibitor:	0.034	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.273
CYP2C9-inhibitor:	0.02	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.612	CYP2D6-substrate:	0.694
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.007
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.971
HLM stability:	0.923 ? 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):

11.103

Half-life (T1/2):

1.96

ADMET: Toxicity

hERG Blockers:	0.064	hERG Blockers (10um):	0.559
Human Hepatotoxicity (H-HT):	0.345	Drug-induced Liver Injury (DILI):	0.827
AMES Toxicity:	0.481	Rat Oral Acute Toxicity:	0.414
Maximum Recommended Daily Dose:	0.53	Skin Sensitization:	0.925
Carcinogencity:	0.522	Eye Corrosion:	0.331
Eye Irritation:	0.992	Respiratory Toxicity:	0.578
Drug-induced Neurotoxicity:	0.021	Ototoxicity:	0.329
Hematotoxicity:	0.08	Drug-induced Nephrotoxicity:	0.03
Genotoxicity:	0.762	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.627	Hek293 Cytotoxicity:	0.295
BCF:	0.89 ? 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:	3.519 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.501 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.194 ? 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
NPO21447	Lotus corniculatus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25177	Balsamorhiza deltoidea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44124	Parthenium rollinsianum	Genus	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21447	Lotus corniculatus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21447	Lotus corniculatus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21447	Lotus corniculatus	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25177	Balsamorhiza deltoidea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21447	Lotus corniculatus	Species	Fabaceae	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 NPC503454 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	30112
0.1-0.2	16501
0.2-0.3	2370
0.3-0.4	675
0.4-0.5	138
0.5-0.6	39
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
0.7222	Intermediate Similarity	NPC87125
0.7091	Intermediate Similarity	NPC305663
0.7091	Intermediate Similarity	NPC162313
0.6727	Remote Similarity	NPC98661
0.6415	Remote Similarity	NPC77858
0.6377	Remote Similarity	NPC245014
0.6207	Remote Similarity	NPC32420
0.6034	Remote Similarity	NPC198826
0.6034	Remote Similarity	NPC143799
0.6034	Remote Similarity	NPC270465
0.6034	Remote Similarity	NPC605755
0.5902	Remote Similarity	NPC252933
0.5893	Remote Similarity	NPC179271
0.5833	Remote Similarity	NPC200740
0.5806	Remote Similarity	NPC227192
0.5738	Remote Similarity	NPC93376
0.5738	Remote Similarity	NPC18607
0.5714	Remote Similarity	NPC20791
0.5645	Remote Similarity	NPC133953
0.5593	Remote Similarity	NPC43243
0.5593	Remote Similarity	NPC275722
0.5593	Remote Similarity	NPC152042
0.5574	Remote Similarity	NPC300943
0.5574	Remote Similarity	NPC212678
0.55	Remote Similarity	NPC57030
0.55	Remote Similarity	NPC188871
0.5484	Remote Similarity	NPC283600
0.5479	Remote Similarity	NPC84265
0.5439	Remote Similarity	NPC195351
0.541	Remote Similarity	NPC108406
0.541	Remote Similarity	NPC49824
0.5397	Remote Similarity	NPC125062
0.5385	Remote Similarity	NPC259411
0.5323	Remote Similarity	NPC54394
0.5323	Remote Similarity	NPC166753
0.5263	Remote Similarity	NPC51443
0.5263	Remote Similarity	NPC27208
0.5246	Remote Similarity	NPC214138
0.5246	Remote Similarity	NPC610660
0.5231	Remote Similarity	NPC485299
0.52	Remote Similarity	NPC117260
0.5167	Remote Similarity	NPC26227
0.5161	Remote Similarity	NPC269652
0.5161	Remote Similarity	NPC25270
0.5161	Remote Similarity	NPC18772
0.5161	Remote Similarity	NPC480465
0.5082	Remote Similarity	NPC44079
0.5079	Remote Similarity	NPC55205
0.5077	Remote Similarity	NPC157784
0.5063	Remote Similarity	NPC477848

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC503454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5864
0.1-0.2	3228
0.2-0.3	51
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
0.5714	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