NPASS Compound

Natural Product: NPC572299

Natural Product ID	NPC572299
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Piscerygenin
IUPAC Name	3-(2,4-dihydroxy-5-methoxy-phenyl)-5,7-dihydroxy-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 35 37 0 0 0 0 0 0 0 0999 V2000 -4.4964 -1.6426 -1.1612 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5968 -0.5082 -0.3621 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5316 0.1278 0.2495 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2255 -0.2980 0.1346 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1958 0.3925 0.7801 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1693 -0.0599 0.6547 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7201 -0.9640 1.5339 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9550 -1.3883 1.4399 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7296 -0.9528 0.4769 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0487 -1.3849 0.3491 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8740 -0.9369 -0.6564 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1834 -1.3756 -0.7704 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3990 -0.0321 -1.5758 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1073 0.4166 -1.4837 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6347 1.3430 -2.4322 O 0 0 0 0 0 0 0 0 0 0 0 0 2.3039 -0.0424 -0.4754 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9801 0.4008 -0.3596 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5269 1.2307 -1.1938 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4527 1.5126 1.5461 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4169 2.2012 2.1911 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7531 1.9301 1.6559 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7693 1.2480 1.0184 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.0979 1.6918 1.1429 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3610 -1.6466 -1.8719 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5396 -1.6960 -1.7208 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5588 -2.5990 -0.5846 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0163 -1.1726 -0.4623 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0804 -1.3231 2.3285 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4248 -2.0954 1.0696 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4858 -2.1571 -0.1890 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0202 0.3405 -2.3782 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7731 2.3378 -2.3006 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0578 1.7739 3.0342 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9671 2.8163 2.2604 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3793 2.5119 0.6280 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 9 10 2 0 10 11 1 0 11 12 1 0 11 13 2 0 13 14 1 0 14 15 1 0 14 16 2 0 16 17 1 0 17 18 2 0 5 19 2 0 19 20 1 0 19 21 1 0 21 22 2 0 22 23 1 0 22 3 1 0 17 6 1 0 16 9 1 0 1 24 1 0 1 25 1 0 1 26 1 0 4 27 1 0 7 28 1 0 10 29 1 0 12 30 1 0 13 31 1 0 15 32 1 0 20 33 1 0 21 34 1 0 23 35 1 0 M END

Standard InCHIKey	OEWYVOHIQUVAAO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H12O7/c1-22-13-4-8(10(18)5-11(13)19)9-6-23-14-3-7(17)2-12(20)15(14)16(9)21/h2-6,17-20H,1H3
SMILES	COC1=CC(C2=COC3=CC(O)=CC(O)=C3C2=O)=C(O)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	316.06	Volume:	300.063 ? Van der Waals volume.
Dense:	1.053	LogP:	1.476 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.748 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.223 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	18.0
TPSA:	120.36 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	4.0	Rings:	3.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.572	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.61	Fsp³:	0.062
MCE-18:	19.0 ? 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:	0
Colloidal aggregators:	0.699	Fluc inhibitor:	0.356 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.806 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.548 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.548	Promiscuous compounds:	0.865

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.196	MDCK Permeability:	-4.858
Pgp-inhibitor:	0.022	Pgp-substrate:	0.369
PAMPA:	0.17 ? 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):	0.003
20% Bioavailability (F20%):	0.211	30% Bioavailability (F30%):	0.789
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.007	MRP1:	0.699
Plasma Protein Binding (PPB):	96.298%	Volume Distribution (VD):	-0.519
Fu:	3.94% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.919
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.983
BSEP inhibitor:	0.228

ADMET: Metabolism

CYP1A2-inhibitor:	0.944	CYP1A2-substrate:	0.648
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.011
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.974
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.932
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.62
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.453 ? 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):

0.994

Half-life (T1/2):

1.998

ADMET: Toxicity

hERG Blockers:	0.083	hERG Blockers (10um):	0.526
Human Hepatotoxicity (H-HT):	0.43	Drug-induced Liver Injury (DILI):	0.719
AMES Toxicity:	0.626	Rat Oral Acute Toxicity:	0.561
Maximum Recommended Daily Dose:	0.849	Skin Sensitization:	0.547
Carcinogencity:	0.682	Eye Corrosion:	0.045
Eye Irritation:	0.993	Respiratory Toxicity:	0.891
Drug-induced Neurotoxicity:	0.084	Ototoxicity:	0.153
Hematotoxicity:	0.064	Drug-induced Nephrotoxicity:	0.104
Genotoxicity:	0.941	RPMI-8226 Immunitoxicity:	0.115
A549 Cytotoxicity:	0.477	Hek293 Cytotoxicity:	0.733
BCF:	0.995 ? 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:	3.581 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.295 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.663 ? 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
NPO44819	Piscidia erythrina	Genus	Fabaceae	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 NPC572299 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	29751
0.1-0.2	17286
0.2-0.3	2170
0.3-0.4	484
0.4-0.5	116
0.5-0.6	24
0.6-0.7	16
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
0.7818	Intermediate Similarity	NPC19980
0.7414	Intermediate Similarity	NPC45291
0.7119	Intermediate Similarity	NPC254702
0.6949	Remote Similarity	NPC279668
0.6949	Remote Similarity	NPC481044
0.6842	Remote Similarity	NPC78341
0.6833	Remote Similarity	NPC264550
0.6667	Remote Similarity	NPC194653
0.661	Remote Similarity	NPC239363
0.65	Remote Similarity	NPC200316
0.6441	Remote Similarity	NPC294409
0.6441	Remote Similarity	NPC490701
0.6316	Remote Similarity	NPC87545
0.629	Remote Similarity	NPC142876
0.629	Remote Similarity	NPC483637
0.623	Remote Similarity	NPC309154
0.6129	Remote Similarity	NPC278323
0.6094	Remote Similarity	NPC167595
0.6032	Remote Similarity	NPC476055
0.5789	Remote Similarity	NPC193792
0.5735	Remote Similarity	NPC268059
0.5692	Remote Similarity	NPC104728
0.569	Remote Similarity	NPC39426
0.569	Remote Similarity	NPC608554
0.5652	Remote Similarity	NPC280937
0.5652	Remote Similarity	NPC479305
0.5652	Remote Similarity	NPC128774
0.5507	Remote Similarity	NPC233918
0.55	Remote Similarity	NPC38065
0.5493	Remote Similarity	NPC482075
0.5385	Remote Similarity	NPC90665
0.5278	Remote Similarity	NPC231763
0.5217	Remote Similarity	NPC232947
0.5152	Remote Similarity	NPC156953
0.5147	Remote Similarity	NPC93552
0.5139	Remote Similarity	NPC474052
0.5128	Remote Similarity	NPC481043
0.5077	Remote Similarity	NPC250557
0.5075	Remote Similarity	NPC291802
0.5075	Remote Similarity	NPC114192
0.5072	Remote Similarity	NPC238279
0.5072	Remote Similarity	NPC608523
0.5068	Remote Similarity	NPC74178

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC572299 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5985
0.1-0.2	3127
0.2-0.3	33
0.3-0.4	4
0.4-0.5	0
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
0.569	Remote Similarity	NPD1510	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