NPASS Compound

Natural Product: NPC515719

Natural Product ID	NPC515719
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3-oxo-3-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)-7-methoxy-4-oxo-chromen-5-yl]oxy-tetrahydropyran-2-yl]methoxy]propanoic acid
IUPAC Name	3-oxo-3-[[(2~{R},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-[2-(4-hydroxyphenyl)-7-methoxy-4-oxo-chromen-5-yl]oxy-tetrahydropyran-2-yl]methoxy]propanoic acid
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 62 65 0 0 0 0 0 0 0 0999 V2000 -2.2667 1.1381 6.0552 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1342 1.1061 5.2070 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3886 0.8609 3.8387 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3681 0.8089 2.9380 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5643 0.5662 1.5553 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4573 0.5377 0.7910 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4820 0.5076 0.0167 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5572 -0.3163 0.4739 O 0 0 0 0 0 0 0 0 0 0 0 0 3.4422 -0.5915 -0.5666 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8736 -0.5955 -0.0608 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7407 -0.9039 -1.1056 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7102 -2.1118 -1.7513 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8936 -2.9924 -1.4108 O 0 0 0 0 0 0 0 0 0 0 0 0 6.6864 -2.3206 -2.8641 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8866 -2.9902 -2.3054 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9504 -3.2795 -1.0895 O 0 0 0 0 0 0 0 0 0 0 0 0 8.9422 -3.2850 -3.1912 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3525 0.3457 -1.7240 C 0 0 2 0 0 0 0 0 0 0 0 0 4.6164 0.3645 -2.3581 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0670 1.7603 -1.3436 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2559 2.5081 -1.2214 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2094 1.8890 -0.1295 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0279 2.0035 0.9896 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9068 0.3786 1.1601 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1818 0.1405 -0.1677 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2667 0.0857 -1.0219 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5225 -0.0379 -0.5245 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5419 0.0180 0.3958 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9512 -0.1687 0.0141 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9096 -0.1103 1.0278 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2597 -0.2594 0.7792 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7054 -0.4763 -0.5149 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.0591 -0.6309 -0.8010 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.7527 -0.5326 -1.5052 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3845 -0.3817 -1.2567 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2003 0.2476 1.6369 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.9538 0.4266 2.0473 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6623 0.6680 3.3724 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8596 0.1995 5.9802 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0029 1.2932 7.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9044 1.9939 5.6883 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6352 0.9662 3.3266 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3517 0.1208 -1.0531 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1706 -1.5952 -0.9315 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1623 0.4411 0.2831 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9710 -1.3094 0.7856 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1631 -2.9815 -3.6099 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9371 -1.3401 -3.3145 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7799 -3.7223 -2.7920 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6623 -0.0320 -2.5350 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9716 1.2562 -2.4976 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5019 2.2705 -2.1787 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0459 3.4615 -1.0639 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4635 2.6844 -0.1817 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7817 2.8088 1.5410 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7446 -0.2254 -1.5588 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5464 0.0574 2.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9961 -0.2132 1.5692 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.5084 -0.0882 -1.5439 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0652 -0.6983 -2.5293 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6632 -0.4326 -2.0553 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4784 0.7075 4.0739 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 15 17 1 0 9 18 1 0 18 19 1 0 18 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 5 24 2 0 24 25 1 0 25 26 2 0 25 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 32 34 1 0 34 35 2 0 28 36 1 0 36 37 1 0 37 38 2 0 38 3 1 0 22 7 1 0 37 24 1 0 35 29 1 0 1 39 1 0 1 40 1 0 1 41 1 0 4 42 1 0 7 43 1 6 9 44 1 6 10 45 1 0 10 46 1 0 14 47 1 0 14 48 1 0 17 49 1 0 18 50 1 6 19 51 1 0 20 52 1 6 21 53 1 0 22 54 1 6 23 55 1 0 27 56 1 0 30 57 1 0 31 58 1 0 33 59 1 0 34 60 1 0 35 61 1 0 38 62 1 0 M END

Standard InCHIKey	WZEYEVDCZWOQJH-FYOOOJEWSA-N
Standard InCHI	InChI=1S/C25H24O13/c1-34-13-6-16-21(14(27)8-15(36-16)11-2-4-12(26)5-3-11)17(7-13)37-25-24(33)23(32)22(31)18(38-25)10-35-20(30)9-19(28)29/h2-8,18,22-26,31-33H,9-10H2,1H3,(H,28,29)/t18-,22+,23+,24+,25-/m1/s1
SMILES	COC1=CC(O[C@@H]2O[C@H](COC(=O)CC(=O)O)[C@H](O)[C@H](O)[C@@H]2O)=C2C(=O)C=C(C3=CC=C(O)C=C3)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	532.12	Volume:	494.639 ? Van der Waals volume.
Dense:	1.076	LogP:	1.038 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.475 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.113 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	26.0
TPSA:	202.42 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.197	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.997	Fsp³:	0.32
MCE-18:	89.182 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.489	Fluc inhibitor:	0.307 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.964 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.859 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.026	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.075	MDCK Permeability:	-5.292
Pgp-inhibitor:	0.0	Pgp-substrate:	0.101
PAMPA:	1.0 ? 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):	0.162
20% Bioavailability (F20%):	0.715	30% Bioavailability (F30%):	0.786
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.791
Plasma Protein Binding (PPB):	83.707%	Volume Distribution (VD):	-0.068
Fu:	18.103% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.963
OATP1B3 inhibitor:	0.997	BCRP inhibitor:	0.006
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.017	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.345
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.008
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.996
HLM stability:	0.045 ? 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):

0.975

Half-life (T1/2):

2.068

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.019
Human Hepatotoxicity (H-HT):	0.593	Drug-induced Liver Injury (DILI):	0.995
AMES Toxicity:	0.964	Rat Oral Acute Toxicity:	0.239
Maximum Recommended Daily Dose:	0.29	Skin Sensitization:	1.0
Carcinogencity:	0.674	Eye Corrosion:	0.0
Eye Irritation:	0.754	Respiratory Toxicity:	0.222
Drug-induced Neurotoxicity:	0.09	Ototoxicity:	0.58
Hematotoxicity:	0.832	Drug-induced Nephrotoxicity:	0.911
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.12
A549 Cytotoxicity:	0.443	Hek293 Cytotoxicity:	0.552
BCF:	0.28 ? 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:	2.892 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.271 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.544 ? 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
NPO21528	Equisetum arvense	Species	Equisetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21528	Equisetum arvense	Species	Equisetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21528	Equisetum arvense	Species	Equisetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21528	Equisetum arvense	Species	Equisetaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21528	Equisetum arvense	Species	Equisetaceae	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 NPC515719 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	16441
0.1-0.2	29742
0.2-0.3	2727
0.3-0.4	687
0.4-0.5	212
0.5-0.6	35
0.6-0.7	7
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
0.7753	Intermediate Similarity	NPC64051
0.7528	Intermediate Similarity	NPC129827
0.7174	Intermediate Similarity	NPC46202
0.7143	Intermediate Similarity	NPC473512
0.7021	Intermediate Similarity	NPC229409
0.6739	Remote Similarity	NPC295613
0.6591	Remote Similarity	NPC610763
0.6383	Remote Similarity	NPC473657
0.6344	Remote Similarity	NPC172807
0.6316	Remote Similarity	NPC15358
0.6289	Remote Similarity	NPC284277
0.6117	Remote Similarity	NPC121703
0.596	Remote Similarity	NPC475497
0.58	Remote Similarity	NPC475366
0.5784	Remote Similarity	NPC270675
0.5784	Remote Similarity	NPC195685
0.5701	Remote Similarity	NPC472993
0.567	Remote Similarity	NPC211594
0.5657	Remote Similarity	NPC44931
0.5652	Remote Similarity	NPC110349
0.5638	Remote Similarity	NPC182045
0.5631	Remote Similarity	NPC479766
0.5619	Remote Similarity	NPC472994
0.5612	Remote Similarity	NPC254540
0.5577	Remote Similarity	NPC479765
0.5521	Remote Similarity	NPC284960
0.5484	Remote Similarity	NPC83283
0.5474	Remote Similarity	NPC27942
0.5377	Remote Similarity	NPC101636
0.5377	Remote Similarity	NPC298171
0.5315	Remote Similarity	NPC277532
0.5294	Remote Similarity	NPC22062
0.5294	Remote Similarity	NPC473634
0.5294	Remote Similarity	NPC138811
0.5213	Remote Similarity	NPC331652
0.5189	Remote Similarity	NPC488089
0.5158	Remote Similarity	NPC39360
0.5158	Remote Similarity	NPC29763
0.5158	Remote Similarity	NPC210003
0.514	Remote Similarity	NPC477629
0.5104	Remote Similarity	NPC93337
0.5102	Remote Similarity	NPC282169
0.5096	Remote Similarity	NPC204693
0.5094	Remote Similarity	NPC473623
0.5052	Remote Similarity	NPC105025
0.505	Remote Similarity	NPC477848
0.5046	Remote Similarity	NPC470450

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC515719 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3621
0.1-0.2	5406
0.2-0.3	113
0.3-0.4	3
0.4-0.5	6
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
0.566	Remote Similarity	NPD7472	Pre-clinical

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