NPASS Compound

Natural Product: NPC590843

Natural Product ID	NPC590843
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Leucanthogenin
IUPAC Name	2-(3,4-dihydroxyphenyl)-5,8-dihydroxy-6,7-dimethoxy-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 39 41 0 0 0 0 0 0 0 0999 V2000 4.1954 -2.8300 1.1299 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7011 -2.2671 -0.0451 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8519 -1.1762 -0.1150 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3717 0.0781 -0.1950 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7454 0.2925 -0.2083 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4191 0.4767 1.0219 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5794 1.2188 -0.2680 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1007 2.5017 -0.3499 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2145 1.0747 -0.2592 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3575 2.1663 -0.3291 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8902 3.3010 -0.4015 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0024 1.9401 -0.3150 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5081 0.6641 -0.2336 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9377 0.3957 -0.2169 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3647 -0.9184 -0.1331 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7071 -1.2377 -0.1130 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6812 -0.2643 -0.1754 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0420 -0.5534 -0.1573 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2706 1.0472 -0.2591 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2389 2.0392 -0.3226 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9072 1.3601 -0.2787 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6339 -0.3115 -0.1711 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6530 -0.1880 -0.1787 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4825 -1.3126 -0.1066 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8912 -2.5790 -0.0259 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9550 -3.9314 1.1128 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8077 -2.3645 2.0578 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3206 -2.7890 1.1243 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2464 1.2177 0.9302 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7275 0.9113 1.8025 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8443 -0.4629 1.4264 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6796 2.6952 -1.1777 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6390 2.8049 -0.3704 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6019 -1.7062 -0.0825 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0369 -2.2744 -0.0469 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4466 -1.2467 -0.7900 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3268 2.5279 -1.2008 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6229 2.3869 -0.3442 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0666 -2.6868 -0.3707 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 4 7 1 0 7 8 1 0 7 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 17 19 1 0 19 20 1 0 19 21 2 0 13 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 24 3 1 0 23 9 1 0 21 14 1 0 1 26 1 0 1 27 1 0 1 28 1 0 6 29 1 0 6 30 1 0 6 31 1 0 8 32 1 0 12 33 1 0 15 34 1 0 16 35 1 0 18 36 1 0 20 37 1 0 21 38 1 0 25 39 1 0 M END

Standard InCHIKey	VZNIMRVJHRTTKA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O8/c1-23-16-13(21)12-10(20)6-11(7-3-4-8(18)9(19)5-7)25-15(12)14(22)17(16)24-2/h3-6,18-19,21-22H,1-2H3
SMILES	COC1=C(OC)C(O)=C2C(=O)C=C(C3=CC=C(O)C(O)=C3)OC2=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.07	Volume:	326.149 ? Van der Waals volume.
Dense:	1.061	LogP:	1.873 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.909 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.863 ? 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:	0.42	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.688	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:	0.742	Fluc inhibitor:	0.506 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.869 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.592 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.432	Promiscuous compounds:	0.903

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.179	MDCK Permeability:	-4.808
Pgp-inhibitor:	0.017	Pgp-substrate:	0.043
PAMPA:	0.338 ? 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):	0.039
20% Bioavailability (F20%):	0.791	30% Bioavailability (F30%):	0.933
50% Bioavailability (F50%):	0.995

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.037	MRP1:	0.983
Plasma Protein Binding (PPB):	97.464%	Volume Distribution (VD):	-0.468
Fu:	2.186% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.962
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.726
BSEP inhibitor:	0.134

ADMET: Metabolism

CYP1A2-inhibitor:	0.019	CYP1A2-substrate:	0.013
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.003
CYP2C9-inhibitor:	0.026	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.706	CYP2D6-substrate:	0.931
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.763
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.903
HLM stability:	0.489 ? 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):

11.117

Half-life (T1/2):

1.684

ADMET: Toxicity

hERG Blockers:	0.072	hERG Blockers (10um):	0.577
Human Hepatotoxicity (H-HT):	0.354	Drug-induced Liver Injury (DILI):	0.822
AMES Toxicity:	0.469	Rat Oral Acute Toxicity:	0.448
Maximum Recommended Daily Dose:	0.577	Skin Sensitization:	0.942
Carcinogencity:	0.616	Eye Corrosion:	0.31
Eye Irritation:	0.985	Respiratory Toxicity:	0.625
Drug-induced Neurotoxicity:	0.03	Ototoxicity:	0.286
Hematotoxicity:	0.113	Drug-induced Nephrotoxicity:	0.039
Genotoxicity:	0.721	RPMI-8226 Immunitoxicity:	0.04
A549 Cytotoxicity:	0.624	Hek293 Cytotoxicity:	0.426
BCF:	1.044 ? 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:	3.651 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.599 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.201 ? 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
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32092043]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36866384]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37151483]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48476	Nepeta spp.	Genus	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO25037	Nepeta cataria	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25037	Nepeta cataria	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 NPC590843 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	30720
0.1-0.2	16093
0.2-0.3	2256
0.3-0.4	565
0.4-0.5	178
0.5-0.6	31
0.6-0.7	5
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8163	Intermediate Similarity	NPC607196
0.7547	Intermediate Similarity	NPC280339
0.7037	Intermediate Similarity	NPC163780
0.7037	Intermediate Similarity	NPC201136
0.7037	Intermediate Similarity	NPC25270
0.6545	Remote Similarity	NPC100887
0.625	Remote Similarity	NPC188203
0.614	Remote Similarity	NPC108406
0.614	Remote Similarity	NPC162313
0.6038	Remote Similarity	NPC17286
0.5789	Remote Similarity	NPC138360
0.569	Remote Similarity	NPC231018
0.569	Remote Similarity	NPC120163
0.5593	Remote Similarity	NPC18772
0.5593	Remote Similarity	NPC604569
0.5593	Remote Similarity	NPC605047
0.5517	Remote Similarity	NPC187498
0.5424	Remote Similarity	NPC604462
0.5417	Remote Similarity	NPC45638
0.541	Remote Similarity	NPC160951
0.541	Remote Similarity	NPC196439
0.5357	Remote Similarity	NPC275772
0.5342	Remote Similarity	NPC201292
0.5333	Remote Similarity	NPC22472
0.5333	Remote Similarity	NPC32420
0.5323	Remote Similarity	NPC227325
0.5323	Remote Similarity	NPC47781
0.5263	Remote Similarity	NPC279121
0.5254	Remote Similarity	NPC71334
0.5254	Remote Similarity	NPC241498
0.5254	Remote Similarity	NPC275836
0.5254	Remote Similarity	NPC239128
0.5238	Remote Similarity	NPC258331
0.5167	Remote Similarity	NPC176775
0.5167	Remote Similarity	NPC145379
0.5167	Remote Similarity	NPC163524
0.5088	Remote Similarity	NPC296197
0.5085	Remote Similarity	NPC250822
0.5085	Remote Similarity	NPC75279
0.5082	Remote Similarity	NPC208197
0.5082	Remote Similarity	NPC256283

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC590843 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5739
0.1-0.2	3348
0.2-0.3	55
0.3-0.4	6
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
0.5263	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