NPASS Compound

Natural Product: NPC513267

Natural Product ID	NPC513267
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Zanthoxyl flavone
IUPAC Name	2-(3,4-dihydroxyphenyl)-3,5-dihydroxy-7,8-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 -5.6181 1.4228 -0.0377 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2349 1.5718 -0.1476 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3315 0.5406 0.1408 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7547 -0.7103 0.5590 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8172 -1.6952 0.8311 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1897 -2.9625 1.2523 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4756 -1.4149 0.6812 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5429 -2.3856 0.9489 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8516 -3.5305 1.3282 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8082 -2.0455 0.7795 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7262 -3.0709 1.0653 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2030 -0.8128 0.3683 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5775 -0.4162 0.1798 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6439 -1.2123 0.3858 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9348 -0.7187 0.1701 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1702 0.5727 -0.2526 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4461 1.0340 -0.4573 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0925 1.3851 -0.4633 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2617 2.6806 -0.8844 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8272 0.8940 -0.2496 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2419 0.0829 0.1258 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0174 -0.1689 0.2629 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9838 0.7709 0.0065 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5581 2.0235 -0.4124 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4226 2.1927 -1.8301 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0890 2.3600 -0.4001 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8561 1.2467 1.0356 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9229 0.5629 -0.6771 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7974 -0.9066 0.6687 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0331 -3.2250 2.2272 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8247 -3.8541 0.4542 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5995 -2.2337 0.7138 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7741 -1.3828 0.3443 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5817 1.6849 -1.2426 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8604 3.4891 -0.4198 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9984 1.5852 -0.4328 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8258 3.0925 -2.0734 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8668 1.2922 -2.2093 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3830 2.2614 -2.3394 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 5 7 2 0 7 8 1 0 8 9 2 0 8 10 1 0 10 11 1 0 10 12 2 0 12 13 1 0 13 14 2 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 12 21 1 0 21 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 23 3 1 0 22 7 1 0 20 13 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 6 30 1 0 11 31 1 0 14 32 1 0 15 33 1 0 17 34 1 0 19 35 1 0 20 36 1 0 25 37 1 0 25 38 1 0 25 39 1 0 M END

Standard InCHIKey	SYFVLDHARWXXFR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C17H14O8/c1-23-11-6-10(20)12-13(21)14(22)15(25-17(12)16(11)24-2)7-3-4-8(18)9(19)5-7/h3-6,18-20,22H,1-2H3
SMILES	COC1=CC(O)=C2C(=O)C(O)=C(C3=CC=C(O)C(O)=C3)OC2=C1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	346.07	Volume:	326.149 ? Van der Waals volume.
Dense:	1.061	LogP:	1.646 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.806 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.833 ? 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:	2.588	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:	0.71	Fluc inhibitor:	0.336 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.926 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.462 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.391	Promiscuous compounds:	0.844

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.335	MDCK Permeability:	-4.831
Pgp-inhibitor:	0.06	Pgp-substrate:	0.014
PAMPA:	0.282 ? 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):	0.182
20% Bioavailability (F20%):	0.664	30% Bioavailability (F30%):	0.971
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.873
Plasma Protein Binding (PPB):	97.614%	Volume Distribution (VD):	-0.678
Fu:	2.238% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.976
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.967
BSEP inhibitor:	0.416

ADMET: Metabolism

CYP1A2-inhibitor:	0.049	CYP1A2-substrate:	0.006
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.098
CYP2C9-inhibitor:	0.119	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.841	CYP2D6-substrate:	0.914
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.018
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.342
HLM stability:	0.811 ? 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):

10.611

Half-life (T1/2):

1.769

ADMET: Toxicity

hERG Blockers:	0.068	hERG Blockers (10um):	0.556
Human Hepatotoxicity (H-HT):	0.395	Drug-induced Liver Injury (DILI):	0.821
AMES Toxicity:	0.523	Rat Oral Acute Toxicity:	0.461
Maximum Recommended Daily Dose:	0.505	Skin Sensitization:	0.88
Carcinogencity:	0.577	Eye Corrosion:	0.252
Eye Irritation:	0.984	Respiratory Toxicity:	0.657
Drug-induced Neurotoxicity:	0.034	Ototoxicity:	0.319
Hematotoxicity:	0.131	Drug-induced Nephrotoxicity:	0.052
Genotoxicity:	0.704	RPMI-8226 Immunitoxicity:	0.041
A549 Cytotoxicity:	0.564	Hek293 Cytotoxicity:	0.314
BCF:	1.068 ? 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:	3.621 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.443 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.977 ? 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
NPO48469	Zanthoxylum alatum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC513267 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	29532
0.1-0.2	17136
0.2-0.3	2406
0.3-0.4	600
0.4-0.5	142
0.5-0.6	30
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8519	High Similarity	NPC259411
0.7885	Intermediate Similarity	NPC301123
0.7736	Intermediate Similarity	NPC86485
0.7241	Intermediate Similarity	NPC480464
0.7091	Intermediate Similarity	NPC607913
0.6909	Remote Similarity	NPC87125
0.6786	Remote Similarity	NPC32420
0.625	Remote Similarity	NPC606048
0.614	Remote Similarity	NPC98661
0.6034	Remote Similarity	NPC605144
0.5763	Remote Similarity	NPC143799
0.5763	Remote Similarity	NPC270465
0.5763	Remote Similarity	NPC605755
0.5738	Remote Similarity	NPC610401
0.5667	Remote Similarity	NPC480465
0.5645	Remote Similarity	NPC152166
0.5614	Remote Similarity	NPC179271
0.5593	Remote Similarity	NPC189960
0.5593	Remote Similarity	NPC306821
0.5574	Remote Similarity	NPC178854
0.5536	Remote Similarity	NPC27208
0.55	Remote Similarity	NPC201451
0.55	Remote Similarity	NPC32557
0.55	Remote Similarity	NPC188871
0.55	Remote Similarity	NPC608038
0.5484	Remote Similarity	NPC189179
0.5484	Remote Similarity	NPC224137
0.5484	Remote Similarity	NPC474520
0.5484	Remote Similarity	NPC603112
0.5439	Remote Similarity	NPC20791
0.541	Remote Similarity	NPC108406
0.5397	Remote Similarity	NPC252933
0.5333	Remote Similarity	NPC152042
0.5325	Remote Similarity	NPC295082
0.5323	Remote Similarity	NPC200740
0.5323	Remote Similarity	NPC166753
0.5263	Remote Similarity	NPC77858
0.5161	Remote Similarity	NPC22472
0.5161	Remote Similarity	NPC201136
0.5152	Remote Similarity	NPC603082

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC513267 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5538
0.1-0.2	3554
0.2-0.3	52
0.3-0.4	3
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
0.5439	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