NPASS Compound

Natural Product: NPC544513

Natural Product ID	NPC544513
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Artemexitin
IUPAC Name	2-(3,4-dihydroxy-5-methoxy-phenyl)-5,7-dihydroxy-3-methoxy-chromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0002585] O-methylated flavonoids [CHEMONTID:0002588] 3-O-methylated flavonoids

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 39 41 0 0 0 0 0 0 0 0999 V2000 3.6755 2.8039 -0.1426 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2073 1.5123 -0.1917 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4122 0.3748 -0.1834 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0362 0.4318 -0.1259 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2198 -0.6892 -0.1162 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2116 -0.4848 -0.1033 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1175 -1.4712 0.1697 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7690 -2.7839 0.4764 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5909 -3.1925 1.8339 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4802 -1.1346 0.1463 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3337 -1.9988 0.3857 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8578 0.1421 -0.1398 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2002 0.5304 -0.1753 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1239 -0.4609 0.0969 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5708 1.8225 -0.4644 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6166 2.7755 -0.7289 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9782 4.1042 -1.0271 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2956 2.3887 -0.6929 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9003 1.1012 -0.4059 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6531 0.7445 -0.3743 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8013 -1.9131 -0.1672 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1853 -1.9891 -0.2247 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7818 -3.2513 -0.2758 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9773 -0.8703 -0.2328 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3633 -0.9760 -0.2911 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8066 2.9266 -0.8169 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4687 3.1179 0.9021 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4519 3.5329 -0.5125 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6134 1.4416 -0.0872 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0369 -4.1075 1.8454 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1531 -2.3919 2.4552 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5670 -3.4905 2.2872 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3196 -1.1313 -0.6421 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6083 2.1107 -0.4891 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2373 4.7036 -0.2656 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5335 3.1435 -0.9027 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2787 -2.8500 -0.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9453 -3.6390 -1.2137 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8571 -0.8830 0.5889 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 1 0 7 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 13 15 1 0 15 16 2 0 16 17 1 0 16 18 1 0 18 19 2 0 19 20 1 0 5 21 2 0 21 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 24 3 1 0 20 6 1 0 19 12 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 9 30 1 0 9 31 1 0 9 32 1 0 14 33 1 0 15 34 1 0 17 35 1 0 18 36 1 0 21 37 1 0 23 38 1 0 25 39 1 0 M END

Standard InCHIKey	ZMQFEBINFTWTLH-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O8/c1-23-12-4-7(3-10(20)14(12)21)16-17(24-2)15(22)13-9(19)5-8(18)6-11(13)25-16/h3-6,18-21H,1-2H3
SMILES	COC1=CC(C2=C(OC)C(=O)C3=C(O)C=C(O)C=C3O2)=CC(O)=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.07	Volume:	326.149 ? Van der Waals volume.
Dense:	1.061	LogP:	1.795 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.85 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.405 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	18.0
TPSA:	129.59 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.532	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.599	Fsp³:	0.118
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:	1
Colloidal aggregators:	0.674	Fluc inhibitor:	0.305 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.904 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.618 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.429	Promiscuous compounds:	0.847

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.211	MDCK Permeability:	-4.827
Pgp-inhibitor:	0.173	Pgp-substrate:	0.122
PAMPA:	0.217 ? 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):	0.058
20% Bioavailability (F20%):	0.199	30% Bioavailability (F30%):	0.83
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.004	MRP1:	0.861
Plasma Protein Binding (PPB):	97.578%	Volume Distribution (VD):	-0.624
Fu:	2.1% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.52
OATP1B3 inhibitor:	0.987	BCRP inhibitor:	0.997
BSEP inhibitor:	0.871

ADMET: Metabolism

CYP1A2-inhibitor:	0.956	CYP1A2-substrate:	0.003
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.272
CYP2C9-inhibitor:	0.069	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.968	CYP2D6-substrate:	0.995
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.935 ? 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):

6.014

Half-life (T1/2):

1.518

ADMET: Toxicity

hERG Blockers:	0.06	hERG Blockers (10um):	0.52
Human Hepatotoxicity (H-HT):	0.414	Drug-induced Liver Injury (DILI):	0.669
AMES Toxicity:	0.541	Rat Oral Acute Toxicity:	0.408
Maximum Recommended Daily Dose:	0.696	Skin Sensitization:	0.813
Carcinogencity:	0.681	Eye Corrosion:	0.47
Eye Irritation:	0.994	Respiratory Toxicity:	0.66
Drug-induced Neurotoxicity:	0.04	Ototoxicity:	0.176
Hematotoxicity:	0.083	Drug-induced Nephrotoxicity:	0.04
Genotoxicity:	0.909	RPMI-8226 Immunitoxicity:	0.046
A549 Cytotoxicity:	0.448	Hek293 Cytotoxicity:	0.539
BCF:	1.008 ? 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:	3.579 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.446 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.906 ? 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
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15165159]
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	stem	n.a.	PMID[22978234]
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	leaf	n.a.	PMID[22978234]
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38538682]
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25496	Artemisia monosperma	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

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 NPC544513 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	31579
0.1-0.2	15302
0.2-0.3	1974
0.3-0.4	639
0.4-0.5	258
0.5-0.6	78
0.6-0.7	5
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	NPC286342
0.7368	Intermediate Similarity	NPC133953
0.7368	Intermediate Similarity	NPC279989
0.7273	Intermediate Similarity	NPC610359
0.7193	Intermediate Similarity	NPC58382
0.7193	Intermediate Similarity	NPC162351
0.7091	Intermediate Similarity	NPC123886
0.7091	Intermediate Similarity	NPC184536
0.7091	Intermediate Similarity	NPC103342
0.7018	Intermediate Similarity	NPC82325
0.6964	Remote Similarity	NPC59951
0.6897	Remote Similarity	NPC603596
0.6562	Remote Similarity	NPC97255
0.6452	Remote Similarity	NPC158874
0.6102	Remote Similarity	NPC120464
0.5882	Remote Similarity	NPC470458
0.5882	Remote Similarity	NPC269285
0.5833	Remote Similarity	NPC28274
0.5821	Remote Similarity	NPC259632
0.5735	Remote Similarity	NPC56786
0.5714	Remote Similarity	NPC183950
0.5574	Remote Similarity	NPC214138
0.5574	Remote Similarity	NPC62536
0.5574	Remote Similarity	NPC163524
0.5574	Remote Similarity	NPC483773
0.5574	Remote Similarity	NPC601901
0.5556	Remote Similarity	NPC52005
0.5556	Remote Similarity	NPC606638
0.5484	Remote Similarity	NPC305663
0.5469	Remote Similarity	NPC125062
0.5467	Remote Similarity	NPC325555
0.5467	Remote Similarity	NPC226304
0.541	Remote Similarity	NPC287979
0.541	Remote Similarity	NPC219330
0.5405	Remote Similarity	NPC470460
0.5397	Remote Similarity	NPC54394
0.5397	Remote Similarity	NPC29841
0.5385	Remote Similarity	NPC483775
0.5323	Remote Similarity	NPC50403
0.5323	Remote Similarity	NPC231772
0.5323	Remote Similarity	NPC149127
0.5323	Remote Similarity	NPC260895
0.5323	Remote Similarity	NPC176665
0.5323	Remote Similarity	NPC188871
0.5312	Remote Similarity	NPC12200
0.5312	Remote Similarity	NPC609179
0.5278	Remote Similarity	NPC276222
0.5278	Remote Similarity	NPC274618
0.5278	Remote Similarity	NPC34531
0.5278	Remote Similarity	NPC118284
0.5278	Remote Similarity	NPC608147
0.527	Remote Similarity	NPC470461
0.5256	Remote Similarity	NPC223747
0.5254	Remote Similarity	NPC175013
0.5246	Remote Similarity	NPC472438
0.5238	Remote Similarity	NPC9609
0.5238	Remote Similarity	NPC600900
0.5231	Remote Similarity	NPC78326
0.5205	Remote Similarity	NPC67037
0.5205	Remote Similarity	NPC255615
0.519	Remote Similarity	NPC203050
0.519	Remote Similarity	NPC225434
0.5167	Remote Similarity	NPC179271
0.5167	Remote Similarity	NPC279121
0.5161	Remote Similarity	NPC266960
0.5156	Remote Similarity	NPC253634
0.5156	Remote Similarity	NPC159103
0.5147	Remote Similarity	NPC153512
0.5135	Remote Similarity	NPC135599
0.5135	Remote Similarity	NPC73855
0.5135	Remote Similarity	NPC113968
0.5135	Remote Similarity	NPC328940
0.5135	Remote Similarity	NPC277174
0.5135	Remote Similarity	NPC476771
0.5135	Remote Similarity	NPC606877
0.5132	Remote Similarity	NPC52550
0.5128	Remote Similarity	NPC609478
0.5079	Remote Similarity	NPC241838
0.5079	Remote Similarity	NPC76376
0.5079	Remote Similarity	NPC146679
0.5077	Remote Similarity	NPC18607
0.5077	Remote Similarity	NPC236223
0.5077	Remote Similarity	NPC206604
0.5067	Remote Similarity	NPC127546
0.5067	Remote Similarity	NPC19388
0.5067	Remote Similarity	NPC240431
0.5067	Remote Similarity	NPC57625
0.5067	Remote Similarity	NPC55786
0.5067	Remote Similarity	NPC173637
0.5067	Remote Similarity	NPC317489
0.5067	Remote Similarity	NPC223424
0.5067	Remote Similarity	NPC476772
0.5067	Remote Similarity	NPC600591

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC544513 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6196
0.1-0.2	2904
0.2-0.3	44
0.3-0.4	3
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
0.5167	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