NPASS Compound

Natural Product: NPC589206

Natural Product ID	NPC589206
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~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-3-methoxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5-hydroxy-3-methoxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-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 55 58 0 0 0 0 0 0 0 0999 V2000 -5.3295 -2.5217 0.5424 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8099 -1.9473 -0.6798 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6184 -1.2560 -0.5355 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4978 0.0725 -0.2992 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6725 0.9380 -0.1799 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4805 2.2476 0.3061 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5057 3.1468 0.4182 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7825 2.7827 0.0486 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8431 3.6844 0.1554 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0234 1.5244 -0.4298 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.2950 1.0986 -0.8195 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.9525 0.6405 -0.5286 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2882 0.6347 -0.1658 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2013 -0.0853 -0.2628 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0490 0.5236 -0.1202 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2284 -0.1809 -0.2123 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4505 0.4862 -0.0603 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7152 -0.0870 -0.1268 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3245 0.0957 1.1190 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5828 -0.4496 1.1787 C 0 0 2 0 0 0 0 0 0 0 0 0 6.0630 -0.4060 2.5786 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3346 0.0774 3.4604 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3003 -0.8934 2.9057 O 0 0 0 0 0 0 0 0 0 0 0 0 6.5484 0.3479 0.3324 C 0 0 1 0 0 0 0 0 0 0 0 0 7.3312 -0.4435 -0.4859 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7519 1.3351 -0.4935 C 0 0 2 0 0 0 0 0 0 0 0 0 5.2244 2.3557 0.2886 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6145 0.5872 -1.1420 C 0 0 1 0 0 0 0 0 0 0 0 0 5.1705 -0.3577 -1.9957 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1196 -1.5313 -0.4545 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0864 -2.1640 -0.6000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2115 -3.5234 -0.8443 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2623 -1.4411 -0.5045 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4793 -2.0690 -0.6487 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5402 -3.2870 -0.8661 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6385 -3.2872 0.9440 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3440 -2.8967 0.4197 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3784 -1.7174 1.3285 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4724 2.5466 0.6021 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3762 4.1580 0.7897 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6965 3.3239 0.5679 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5844 0.1219 -0.7450 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1882 -0.3241 -0.9372 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0839 1.5876 0.0693 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7461 -1.1720 -0.3200 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6020 -1.5305 0.8917 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8401 -0.5440 3.7106 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2194 0.9420 0.9755 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5220 -0.0523 -1.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3625 1.7556 -1.2989 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3041 3.1923 -0.2206 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0677 1.3174 -1.7704 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1849 -1.2678 -1.6220 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0202 -2.1294 -0.5356 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2033 -3.9589 -1.7378 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 2 0 8 9 1 0 8 10 1 0 10 11 1 0 10 12 2 0 4 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 20 24 1 0 24 25 1 0 24 26 1 0 26 27 1 0 26 28 1 0 28 29 1 0 16 30 2 0 30 31 1 0 31 32 1 0 31 33 2 0 33 34 1 0 34 35 2 0 34 3 1 0 12 5 1 0 33 14 1 0 28 18 1 0 1 36 1 0 1 37 1 0 1 38 1 0 6 39 1 0 7 40 1 0 9 41 1 0 11 42 1 0 12 43 1 0 15 44 1 0 18 45 1 6 20 46 1 6 23 47 1 0 24 48 1 1 25 49 1 0 26 50 1 6 27 51 1 0 28 52 1 6 29 53 1 0 30 54 1 0 32 55 1 0 M END

Standard InCHIKey	JIDFZGSERZHTFO-NTKSAMNMSA-N
Standard InCHI	InChI=1S/C22H20O13/c1-32-19-14(26)13-11(25)5-8(33-22-17(29)15(27)16(28)20(35-22)21(30)31)6-12(13)34-18(19)7-2-3-9(23)10(24)4-7/h2-6,15-17,20,22-25,27-29H,1H3,(H,30,31)/t15-,16-,17+,20-,22+/m0/s1
SMILES	COC1=C(C2=CC=C(O)C(O)=C2)OC2=CC(O[C@@H]3O[C@H](C(=O)O)[C@@H](O)[C@H](O)[C@H]3O)=CC(O)=C2C1=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	492.09	Volume:	445.387 ? Van der Waals volume.
Dense:	1.105	LogP:	1.026 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.339 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.322 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	25.0
TPSA:	216.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.231	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.058	Fsp³:	0.273
MCE-18:	94.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.429	Fluc inhibitor:	0.308 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.968 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.871 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.109	Promiscuous compounds:	0.491

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.24	MDCK Permeability:	-5.321
Pgp-inhibitor:	0.0	Pgp-substrate:	0.212
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):	0.464
20% Bioavailability (F20%):	0.166	30% Bioavailability (F30%):	0.836
50% Bioavailability (F50%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.977
Plasma Protein Binding (PPB):	77.781%	Volume Distribution (VD):	-0.42
Fu:	18.1% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.018
OATP1B3 inhibitor:	0.86	BCRP inhibitor:	0.142
BSEP inhibitor:	0.006

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.369
HLM stability:	0.093 ? 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):

2.055

Half-life (T1/2):

4.573

ADMET: Toxicity

hERG Blockers:	0.011	hERG Blockers (10um):	0.083
Human Hepatotoxicity (H-HT):	0.49	Drug-induced Liver Injury (DILI):	0.992
AMES Toxicity:	0.622	Rat Oral Acute Toxicity:	0.056
Maximum Recommended Daily Dose:	0.075	Skin Sensitization:	0.991
Carcinogencity:	0.126	Eye Corrosion:	0.0
Eye Irritation:	0.804	Respiratory Toxicity:	0.047
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.866
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.315
Genotoxicity:	0.986	RPMI-8226 Immunitoxicity:	0.025
A549 Cytotoxicity:	0.156	Hek293 Cytotoxicity:	0.074
BCF:	0.304 ? 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:	2.932 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.345 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.517 ? 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
NPO50100	Viguiera spp.	Genus	Habronematidae	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 NPC589206 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	24396
0.1-0.2	22703
0.2-0.3	1947
0.3-0.4	513
0.4-0.5	241
0.5-0.6	45
0.6-0.7	6
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
0.7792	Intermediate Similarity	NPC20505
0.7342	Intermediate Similarity	NPC235260
0.7342	Intermediate Similarity	NPC155763
0.7125	Intermediate Similarity	NPC282169
0.7037	Intermediate Similarity	NPC608742
0.6875	Remote Similarity	NPC84362
0.6463	Remote Similarity	NPC271692
0.6429	Remote Similarity	NPC188871
0.6386	Remote Similarity	NPC138927
0.6341	Remote Similarity	NPC136042
0.6047	Remote Similarity	NPC610187
0.5977	Remote Similarity	NPC605784
0.593	Remote Similarity	NPC135277
0.593	Remote Similarity	NPC49344
0.5773	Remote Similarity	NPC253685
0.5698	Remote Similarity	NPC46420
0.5682	Remote Similarity	NPC43211
0.5647	Remote Similarity	NPC249281
0.5625	Remote Similarity	NPC486577
0.5581	Remote Similarity	NPC297987
0.5581	Remote Similarity	NPC158674
0.5568	Remote Similarity	NPC611303
0.5556	Remote Similarity	NPC14187
0.5541	Remote Similarity	NPC146679
0.55	Remote Similarity	NPC121703
0.5393	Remote Similarity	NPC237435
0.5393	Remote Similarity	NPC210094
0.5361	Remote Similarity	NPC229409
0.5341	Remote Similarity	NPC27640
0.5333	Remote Similarity	NPC115760
0.5287	Remote Similarity	NPC289667
0.5287	Remote Similarity	NPC19709
0.5287	Remote Similarity	NPC238376
0.5275	Remote Similarity	NPC116458
0.5275	Remote Similarity	NPC246943
0.5263	Remote Similarity	NPC305663
0.5256	Remote Similarity	NPC78326
0.5227	Remote Similarity	NPC277205
0.5227	Remote Similarity	NPC37919
0.5227	Remote Similarity	NPC189142
0.5227	Remote Similarity	NPC77660
0.5222	Remote Similarity	NPC488071
0.5217	Remote Similarity	NPC276377
0.52	Remote Similarity	NPC103904
0.52	Remote Similarity	NPC262094
0.5195	Remote Similarity	NPC270620
0.5161	Remote Similarity	NPC600989
0.5128	Remote Similarity	NPC58382
0.5116	Remote Similarity	NPC276222
0.5116	Remote Similarity	NPC274618
0.5116	Remote Similarity	NPC118284
0.5116	Remote Similarity	NPC608147
0.5111	Remote Similarity	NPC59534
0.5111	Remote Similarity	NPC101191
0.5065	Remote Similarity	NPC18772
0.5048	Remote Similarity	NPC480441

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC589206 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4443
0.1-0.2	4623
0.2-0.3	73
0.3-0.4	6
0.4-0.5	3
0.5-0.6	2
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
0.5393	Remote Similarity	NPD4338	Clinical (unspecified phase)
0.51	Remote Similarity	NPD7251	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