NPASS Compound

Natural Product: NPC569926

Natural Product ID	NPC569926
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-7-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-5-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chroman-4-one
IUPAC Name	(2~{S})-7-hydroxy-2-(3-hydroxy-4-methoxy-phenyl)-5-[(2~{S},3~{R},4~{S},5~{S},6~{S})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-chroman-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 57 60 0 0 0 0 0 0 0 0999 V2000 -8.7455 -0.0015 1.3477 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5172 -0.0161 2.0365 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2984 -0.2956 1.4439 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1794 -0.5930 0.0863 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9302 -0.8614 -0.4342 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7939 -0.8431 0.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4505 -1.1349 -0.2059 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.3604 -0.7616 0.7799 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0479 -0.6230 0.0830 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9982 -1.0056 0.6286 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0084 -0.0348 -1.2473 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2313 0.4385 -1.7240 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3248 0.3244 -0.9082 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6273 0.7133 -1.1693 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5387 -0.3422 -1.1383 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6534 -0.9295 0.1028 C 0 0 1 0 0 0 0 0 0 0 0 0 5.8477 -1.8870 0.0233 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0521 -2.5379 1.2386 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9498 0.0405 1.2022 C 0 0 1 0 0 0 0 0 0 0 0 0 6.3326 0.3224 1.2630 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1574 1.2989 1.1432 C 0 0 2 0 0 0 0 0 0 0 0 0 2.8967 1.1734 1.7243 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1291 1.8239 -0.2518 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4229 2.1303 -0.6420 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2479 0.9838 -2.9770 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0821 1.0596 -3.7409 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0735 1.6080 -5.0139 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1092 0.5835 -3.2410 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1570 0.0264 -1.9767 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3157 -0.4666 -1.4222 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9213 -0.5483 1.6964 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1782 -0.2724 2.2482 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2725 0.0235 3.6144 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6638 0.3665 0.3076 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.4017 0.7312 1.8835 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1495 -1.0239 1.3571 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0712 -0.6056 -0.5255 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8151 -1.0950 -1.4875 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3986 -2.2314 -0.3944 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3047 -1.4943 1.6043 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5960 0.2404 1.1911 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7080 1.1367 -2.1903 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7703 -1.5798 0.3599 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6935 -2.6538 -0.7484 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7715 -1.2895 -0.1951 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0348 -2.6459 1.3890 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7159 -0.4776 2.1706 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4064 1.2171 1.6962 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7010 2.0427 1.8011 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8504 0.3335 2.2476 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4375 2.6928 -0.3642 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5122 2.2350 -1.6285 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1472 1.3588 -3.3897 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6021 2.2879 -5.3309 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0301 0.6256 -3.8036 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0655 -0.5201 2.3664 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9469 0.9532 3.8828 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 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 16 19 1 0 19 20 1 0 19 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 12 25 1 0 25 26 2 0 26 27 1 0 26 28 1 0 28 29 2 0 29 30 1 0 6 31 1 0 31 32 2 0 32 33 1 0 32 3 1 0 30 7 1 0 29 11 1 0 23 14 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 5 38 1 0 7 39 1 6 8 40 1 0 8 41 1 0 14 42 1 6 16 43 1 1 17 44 1 0 17 45 1 0 18 46 1 0 19 47 1 1 20 48 1 0 21 49 1 1 22 50 1 0 23 51 1 1 24 52 1 0 25 53 1 0 27 54 1 0 28 55 1 0 31 56 1 0 33 57 1 0 M END

Standard InCHIKey	QSLBWGKNSBMTJL-NLZCMNGQSA-N
Standard InCHI	InChI=1S/C22H24O11/c1-30-13-3-2-9(4-11(13)25)14-7-12(26)18-15(31-14)5-10(24)6-16(18)32-22-21(29)20(28)19(27)17(8-23)33-22/h2-6,14,17,19-25,27-29H,7-8H2,1H3/t14-,17-,19+,20-,21+,22+/m0/s1
SMILES	COC1=CC=C([C@@H]2CC(=O)C3=C(O[C@@H]4O[C@@H](CO)[C@@H](O)[C@H](O)[C@H]4O)C=C(O)C=C3O2)C=C1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	464.13	Volume:	433.08 ? Van der Waals volume.
Dense:	1.072	LogP:	0.591 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.135 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.8 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	24.0
TPSA:	175.37 ? 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:	0.351	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.116	Fsp³:	0.409
MCE-18:	89.742 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.581	Fluc inhibitor:	0.376 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.264 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.644 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.289

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.489	MDCK Permeability:	-5.284
Pgp-inhibitor:	0.001	Pgp-substrate:	0.037
PAMPA:	0.969 ? 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):	0.029
20% Bioavailability (F20%):	0.208	30% Bioavailability (F30%):	0.878
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.623
Plasma Protein Binding (PPB):	86.354%	Volume Distribution (VD):	-0.195
Fu:	12.693% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.935
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.397
BSEP inhibitor:	0.134

ADMET: Metabolism

CYP1A2-inhibitor:	0.021	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.006
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.07
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.919
HLM stability:	0.107 ? 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):

2.583

Half-life (T1/2):

3.444

ADMET: Toxicity

hERG Blockers:	0.044	hERG Blockers (10um):	0.24
Human Hepatotoxicity (H-HT):	0.804	Drug-induced Liver Injury (DILI):	0.926
AMES Toxicity:	0.891	Rat Oral Acute Toxicity:	0.139
Maximum Recommended Daily Dose:	0.161	Skin Sensitization:	0.985
Carcinogencity:	0.31	Eye Corrosion:	0.0
Eye Irritation:	0.66	Respiratory Toxicity:	0.113
Drug-induced Neurotoxicity:	0.088	Ototoxicity:	0.909
Hematotoxicity:	0.164	Drug-induced Nephrotoxicity:	0.84
Genotoxicity:	0.924	RPMI-8226 Immunitoxicity:	0.176
A549 Cytotoxicity:	0.482	Hek293 Cytotoxicity:	0.332
BCF:	0.349 ? 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:	2.873 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.563 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.59 ? 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
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22472691]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	kernel	n.a.	PMID[7092570]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7651	Citrus spp.	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14992	Prunus persica	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14992	Prunus persica	Species	Rosaceae	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 NPC569926 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	17173
0.1-0.2	27084
0.2-0.3	4447
0.3-0.4	871
0.4-0.5	247
0.5-0.6	25
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	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC5778
0.7826	Intermediate Similarity	NPC169248
0.7826	Intermediate Similarity	NPC72649
0.68	Remote Similarity	NPC206378
0.6447	Remote Similarity	NPC471457
0.6316	Remote Similarity	NPC170475
0.6234	Remote Similarity	NPC219163
0.6234	Remote Similarity	NPC26195
0.6049	Remote Similarity	NPC479540
0.6049	Remote Similarity	NPC236934
0.5897	Remote Similarity	NPC97052
0.5875	Remote Similarity	NPC29830
0.5823	Remote Similarity	NPC39351
0.5696	Remote Similarity	NPC45400
0.5568	Remote Similarity	NPC472876
0.5556	Remote Similarity	NPC105095
0.5556	Remote Similarity	NPC177731
0.5556	Remote Similarity	NPC725
0.5542	Remote Similarity	NPC477502
0.5444	Remote Similarity	NPC44328
0.5444	Remote Similarity	NPC79056
0.5385	Remote Similarity	NPC189115
0.5366	Remote Similarity	NPC279298
0.5357	Remote Similarity	NPC472383
0.5357	Remote Similarity	NPC298847
0.5301	Remote Similarity	NPC181014
0.5294	Remote Similarity	NPC152722
0.519	Remote Similarity	NPC98777
0.5176	Remote Similarity	NPC472381
0.5072	Remote Similarity	NPC188243
0.5072	Remote Similarity	NPC110228
0.5068	Remote Similarity	NPC302950
0.5065	Remote Similarity	NPC199335
0.5065	Remote Similarity	NPC477240
0.5062	Remote Similarity	NPC601828

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC569926 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4147
0.1-0.2	4894
0.2-0.3	91
0.3-0.4	15
0.4-0.5	1
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
0.5444	Remote Similarity	NPD7074	Phase 3
0.5068	Remote Similarity	NPD1934	Phase 0

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