NPASS Compound

Natural Product: NPC493554

Natural Product ID	NPC493554
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-hydroxy-3-(4-hydroxyphenyl)-8-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	5-hydroxy-3-(4-hydroxyphenyl)-8-methoxy-7-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-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 55 58 0 0 0 0 0 0 0 0999 V2000 0.6093 -2.1718 -2.1741 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3282 -1.9957 -0.8011 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1528 -0.8147 -0.2742 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7476 0.1301 0.1611 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0806 -0.1294 0.0587 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1645 0.6469 0.4201 C 0 0 2 0 0 0 0 0 0 0 0 0 4.0093 0.9686 -0.6377 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0449 0.0424 -0.7799 C 0 0 1 0 0 0 0 0 0 0 0 0 5.7534 0.3113 -2.0884 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2902 1.5910 -2.1338 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0180 0.2214 0.3604 C 0 0 1 0 0 0 0 0 0 0 0 0 6.9070 1.2620 0.0518 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2763 0.5659 1.6332 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9696 0.1672 2.7691 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9114 -0.0639 1.5413 C 0 0 1 0 0 0 0 0 0 0 0 0 3.1947 0.1567 2.7165 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2206 1.2918 0.6787 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1504 1.5076 0.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6322 2.6890 1.2880 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0214 0.5312 0.3117 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5218 -0.6407 -0.2107 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3536 -1.5578 -0.6329 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6537 -1.4338 -0.5911 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1946 -0.2836 -0.0788 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6398 -0.1029 -0.0131 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4672 -0.4185 -1.0695 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8305 -0.2424 -0.9928 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4046 0.2595 0.1561 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.7661 0.4367 0.2361 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5836 0.5780 1.2182 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2095 0.3940 1.1238 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3893 0.7142 0.3793 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8439 1.7857 0.8571 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4711 -2.8443 -2.3482 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3212 -2.5426 -2.6483 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8204 -1.1732 -2.6281 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8176 1.6064 0.8486 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6652 -0.9906 -0.8094 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5988 -0.3982 -2.2237 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0817 0.1702 -2.9585 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1149 1.6559 -2.6732 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6233 -0.6859 0.4860 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4169 2.1204 0.2450 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1328 1.6649 1.6925 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6393 -0.5378 2.5962 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9489 -1.1541 1.3889 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1864 -0.6655 3.2966 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8626 2.0769 1.0394 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8926 3.4564 0.6786 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3057 -2.2375 -0.9603 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0515 -0.8129 -1.9822 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4699 -0.4929 -1.8263 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4074 -0.3229 0.4802 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0609 0.9693 2.1056 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5814 0.6454 1.9565 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 8 11 1 0 11 12 1 0 11 13 1 0 13 14 1 0 13 15 1 0 15 16 1 0 4 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 28 30 1 0 30 31 2 0 24 32 1 0 32 33 2 0 21 3 1 0 31 25 1 0 15 6 1 0 32 20 1 0 1 34 1 0 1 35 1 0 1 36 1 0 6 37 1 1 8 38 1 6 9 39 1 0 9 40 1 0 10 41 1 0 11 42 1 1 12 43 1 0 13 44 1 1 14 45 1 0 15 46 1 6 16 47 1 0 17 48 1 0 19 49 1 0 23 50 1 0 26 51 1 0 27 52 1 0 29 53 1 0 30 54 1 0 31 55 1 0 M END

Standard InCHIKey	YJBZWKGFYVMPDY-JEOJHICDSA-N
Standard InCHI	InChI=1S/C22H22O11/c1-30-20-13(32-22-19(29)18(28)17(27)14(7-23)33-22)6-12(25)15-16(26)11(8-31-21(15)20)9-2-4-10(24)5-3-9/h2-6,8,14,17-19,22-25,27-29H,7H2,1H3/t14-,17+,18-,19+,22+/m0/s1
SMILES	COC1=C(O[C@@H]2O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]2O)C=C(O)C2=C1OC=C(C1=CC=C(O)C=C1)C2=O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	462.12	Volume:	430.443 ? Van der Waals volume.
Dense:	1.074	LogP:	0.543 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.252 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.045 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	179.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.302	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.977	Fsp³:	0.318
MCE-18:	86.966 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.517	Fluc inhibitor:	0.273 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.881 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.807 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.096	Promiscuous compounds:	0.534

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.401	MDCK Permeability:	-5.28
Pgp-inhibitor:	0.0	Pgp-substrate:	0.343
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):	0.11
20% Bioavailability (F20%):	0.299	30% Bioavailability (F30%):	0.698
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.338
Plasma Protein Binding (PPB):	85.089%	Volume Distribution (VD):	-0.129
Fu:	15.593% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.685
OATP1B3 inhibitor:	0.749	BCRP inhibitor:	0.248
BSEP inhibitor:	0.057

ADMET: Metabolism

CYP1A2-inhibitor:	0.169	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.023	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.028
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.182
HLM stability:	0.0 ? 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):

2.881

Half-life (T1/2):

3.067

ADMET: Toxicity

hERG Blockers:	0.033	hERG Blockers (10um):	0.308
Human Hepatotoxicity (H-HT):	0.603	Drug-induced Liver Injury (DILI):	0.845
AMES Toxicity:	0.725	Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.071	Skin Sensitization:	0.936
Carcinogencity:	0.214	Eye Corrosion:	0.0
Eye Irritation:	0.341	Respiratory Toxicity:	0.034
Drug-induced Neurotoxicity:	0.023	Ototoxicity:	0.878
Hematotoxicity:	0.157	Drug-induced Nephrotoxicity:	0.559
Genotoxicity:	0.784	RPMI-8226 Immunitoxicity:	0.101
A549 Cytotoxicity:	0.204	Hek293 Cytotoxicity:	0.306
BCF:	0.378 ? 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:	2.923 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.312 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.586 ? 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
NPO20912	Wisteria brachybotrys	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2853205]
NPO20912	Wisteria brachybotrys	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20912	Wisteria brachybotrys	Species	Fabaceae	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 NPC493554 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	18664
0.1-0.2	26761
0.2-0.3	3184
0.3-0.4	970
0.4-0.5	219
0.5-0.6	35
0.6-0.7	12
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
0.7308	Intermediate Similarity	NPC205076
0.7273	Intermediate Similarity	NPC197896
0.7273	Intermediate Similarity	NPC313163
0.7051	Intermediate Similarity	NPC105511
0.6543	Remote Similarity	NPC73511
0.6463	Remote Similarity	NPC100720
0.6386	Remote Similarity	NPC481043
0.622	Remote Similarity	NPC161749
0.622	Remote Similarity	NPC156457
0.618	Remote Similarity	NPC479405
0.6163	Remote Similarity	NPC48773
0.6111	Remote Similarity	NPC479404
0.6098	Remote Similarity	NPC348541
0.6049	Remote Similarity	NPC93099
0.6024	Remote Similarity	NPC603782
0.6	Remote Similarity	NPC80140
0.5904	Remote Similarity	NPC259070
0.5862	Remote Similarity	NPC307518
0.5833	Remote Similarity	NPC258035
0.5814	Remote Similarity	NPC224462
0.5783	Remote Similarity	NPC135345
0.5698	Remote Similarity	NPC138540
0.5647	Remote Similarity	NPC234739
0.5455	Remote Similarity	NPC479401
0.5444	Remote Similarity	NPC479407
0.5412	Remote Similarity	NPC45165
0.5349	Remote Similarity	NPC210042
0.5349	Remote Similarity	NPC44558
0.5333	Remote Similarity	NPC479406
0.5319	Remote Similarity	NPC303913
0.5287	Remote Similarity	NPC323593
0.5287	Remote Similarity	NPC203500
0.5233	Remote Similarity	NPC177308
0.5233	Remote Similarity	NPC160515
0.5227	Remote Similarity	NPC105025
0.5222	Remote Similarity	NPC229729
0.52	Remote Similarity	NPC131266
0.5172	Remote Similarity	NPC39360
0.5172	Remote Similarity	NPC29763
0.5172	Remote Similarity	NPC211014
0.5172	Remote Similarity	NPC210003
0.5155	Remote Similarity	NPC479403
0.5114	Remote Similarity	NPC93337
0.5114	Remote Similarity	NPC297987
0.5111	Remote Similarity	NPC168584
0.5111	Remote Similarity	NPC479402
0.5106	Remote Similarity	NPC480466
0.506	Remote Similarity	NPC78697
0.5056	Remote Similarity	NPC24043
0.5056	Remote Similarity	NPC488080
0.5056	Remote Similarity	NPC169977

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC493554 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5020
0.1-0.2	4020
0.2-0.3	96
0.3-0.4	9
0.4-0.5	3
0.5-0.6	1
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
0.622	Remote Similarity	NPD4381	Clinical (unspecified phase)
0.5412	Remote Similarity	NPD3818	Discontinued

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