NPASS Compound

Natural Product: NPC523170

Natural Product ID	NPC523170
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-[4-(5-hydroxy-6,7-dimethoxy-4-oxo-chromen-2-yl)phenoxy]tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{R},5~{R},6~{S})-3,4,5-trihydroxy-6-[4-(5-hydroxy-6,7-dimethoxy-4-oxo-chromen-2-yl)phenoxy]tetrahydropyran-2-carboxylic 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 57 60 0 0 0 0 0 0 0 0999 V2000 6.7015 -2.0299 -2.4451 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2338 -1.2508 -1.3745 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3641 -0.6094 -0.5186 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9979 -0.7088 -0.6805 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1372 -0.0622 0.1827 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6761 0.6837 1.2081 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0369 0.7765 1.3609 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5161 1.5433 2.4136 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9275 0.1375 0.5086 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2995 0.2492 0.6873 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0408 1.2880 0.0622 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8248 1.3327 2.0748 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2637 2.0301 3.0323 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4585 1.1872 1.8501 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9608 0.4324 0.8134 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5375 0.2573 0.5473 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1218 -0.5218 -0.5208 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2139 -0.7044 -0.7953 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2087 -0.1181 -0.0170 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5181 -0.3453 -0.3516 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6769 0.1252 0.2660 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4490 -0.8914 0.7368 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7379 -0.9660 0.3810 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2434 -2.3453 0.6445 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4481 -2.6580 0.3844 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4151 -3.3164 1.1773 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1066 -0.6022 -1.0139 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.2504 0.1947 -1.0588 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0158 0.1366 -1.7524 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5918 0.9316 -2.7183 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3726 1.0394 -0.7103 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2825 1.8799 -0.1148 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8167 0.6581 1.0467 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4488 0.8255 1.3012 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8396 -0.1532 0.0335 O 0 0 0 0 0 0 0 0 0 0 0 0 7.4909 -2.4581 -3.0708 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0802 -2.8369 -1.9767 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0471 -1.3323 -3.0251 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6102 -1.3153 -1.5134 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6563 2.5611 2.3266 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4547 1.7660 -0.7584 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9612 0.9093 -0.3866 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3462 2.0567 0.8215 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7822 1.6834 2.5122 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8995 -0.9784 -1.1269 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5411 -1.3198 -1.6390 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3999 0.7561 1.1289 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3421 -0.3006 1.0674 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6354 -4.3131 1.0854 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3472 -1.5131 -1.6301 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3295 0.5601 -1.9743 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2337 -0.5438 -2.1400 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2989 1.8614 -2.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6024 1.6338 -1.2373 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9997 2.1082 0.8088 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5467 1.1420 1.6909 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1936 1.4478 2.1528 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 2 0 6 7 1 0 7 8 1 0 7 9 2 0 9 10 1 0 10 11 1 0 6 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 2 0 24 26 1 0 23 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 19 33 1 0 33 34 2 0 15 35 1 0 9 3 1 0 34 16 1 0 35 5 1 0 31 21 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 8 40 1 0 11 41 1 0 11 42 1 0 11 43 1 0 14 44 1 0 17 45 1 0 18 46 1 0 21 47 1 1 23 48 1 1 26 49 1 0 27 50 1 6 28 51 1 0 29 52 1 6 30 53 1 0 31 54 1 6 32 55 1 0 33 56 1 0 34 57 1 0 M END

Standard InCHIKey	FAKLXTCIXLJJOQ-OEBXLPCGSA-N
Standard InCHI	InChI=1S/C23H22O12/c1-31-14-8-13-15(16(25)20(14)32-2)11(24)7-12(34-13)9-3-5-10(6-4-9)33-23-19(28)17(26)18(27)21(35-23)22(29)30/h3-8,17-19,21,23,25-28H,1-2H3,(H,29,30)/t17-,18+,19-,21+,23-/m1/s1
SMILES	COC1=CC2=C(C(O)=C1OC)C(=O)C=C(C1=CC=C(O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@@H](O)[C@H]3O)C=C1)O2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	490.11	Volume:	453.893 ? Van der Waals volume.
Dense:	1.08	LogP:	1.634 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.796 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.789 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	25.0
TPSA:	185.35 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.322	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.891	Fsp³:	0.304
MCE-18:	90.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.357	Fluc inhibitor:	0.376 ? 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:	0.912 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.083	Promiscuous compounds:	0.292

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.066	MDCK Permeability:	-5.435
Pgp-inhibitor:	0.0	Pgp-substrate:	0.663
PAMPA:	0.999 ? 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):	0.073
20% Bioavailability (F20%):	0.022	30% Bioavailability (F30%):	0.059
50% Bioavailability (F50%):	0.729

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.989
Plasma Protein Binding (PPB):	87.362%	Volume Distribution (VD):	-0.209
Fu:	9.922% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.394
OATP1B3 inhibitor:	0.975	BCRP inhibitor:	0.192
BSEP inhibitor:	0.196

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.046	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.973
HLM stability:	0.069 ? 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):

1.684

Half-life (T1/2):

3.824

ADMET: Toxicity

hERG Blockers:	0.029	hERG Blockers (10um):	0.083
Human Hepatotoxicity (H-HT):	0.525	Drug-induced Liver Injury (DILI):	0.907
AMES Toxicity:	0.498	Rat Oral Acute Toxicity:	0.074
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.689
Carcinogencity:	0.162	Eye Corrosion:	0.001
Eye Irritation:	0.659	Respiratory Toxicity:	0.103
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.799
Hematotoxicity:	0.197	Drug-induced Nephrotoxicity:	0.404
Genotoxicity:	0.638	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.019	Hek293 Cytotoxicity:	0.087
BCF:	0.198 ? 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:	3.019 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.219 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.509 ? 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
NPO54713	Conyza linifolia	Genus	Asteraceae	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 NPC523170 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	18703
0.1-0.2	28029
0.2-0.3	2366
0.3-0.4	576
0.4-0.5	140
0.5-0.6	30
0.6-0.7	11
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
0.7922	Intermediate Similarity	NPC608742
0.6914	Remote Similarity	NPC282169
0.6835	Remote Similarity	NPC58053
0.6707	Remote Similarity	NPC237435
0.6707	Remote Similarity	NPC20505
0.6627	Remote Similarity	NPC43211
0.6463	Remote Similarity	NPC186807
0.6429	Remote Similarity	NPC145379
0.6207	Remote Similarity	NPC211594
0.6207	Remote Similarity	NPC600989
0.6047	Remote Similarity	NPC115760
0.6	Remote Similarity	NPC101191
0.593	Remote Similarity	NPC210094
0.593	Remote Similarity	NPC609451
0.5862	Remote Similarity	NPC605067
0.5765	Remote Similarity	NPC93337
0.5747	Remote Similarity	NPC135277
0.5699	Remote Similarity	NPC204693
0.5698	Remote Similarity	NPC105025
0.5698	Remote Similarity	NPC45638
0.5682	Remote Similarity	NPC264735
0.5667	Remote Similarity	NPC172807
0.5638	Remote Similarity	NPC46202
0.5632	Remote Similarity	NPC201292
0.5616	Remote Similarity	NPC239128
0.5604	Remote Similarity	NPC254540
0.56	Remote Similarity	NPC69394
0.5541	Remote Similarity	NPC120163
0.5526	Remote Similarity	NPC160951
0.5521	Remote Similarity	NPC483707
0.5479	Remote Similarity	NPC75279
0.5467	Remote Similarity	NPC25270
0.5402	Remote Similarity	NPC95090
0.5402	Remote Similarity	NPC27408
0.5341	Remote Similarity	NPC181712
0.5333	Remote Similarity	NPC276409
0.53	Remote Similarity	NPC253685
0.5275	Remote Similarity	NPC602805
0.5063	Remote Similarity	NPC47781
0.5055	Remote Similarity	NPC235260
0.5055	Remote Similarity	NPC155763
0.5051	Remote Similarity	NPC229409

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC523170 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3524
0.1-0.2	5479
0.2-0.3	137
0.3-0.4	6
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6707	Remote Similarity	NPD4338	Clinical (unspecified phase)

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