NPASS Compound

Natural Product: NPC517373

Natural Product ID	NPC517373
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R})-5-hydroxy-2-(4-hydroxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-tetrahydropyran-2-yl]oxy-chroman-4-one
IUPAC Name	(2~{R})-5-hydroxy-2-(4-hydroxyphenyl)-7-[(2~{S},3~{R},4~{S},5~{R},6~{R})-3,4,5-trihydroxy-6-methyl-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] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 52 55 0 0 0 0 0 0 0 0999 V2000 -4.1341 3.0270 -0.9948 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1569 1.5321 -0.9449 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7051 1.0381 0.3009 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0553 -0.1787 -0.0088 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4627 -0.7581 1.0963 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1371 -0.9817 1.2817 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7735 -1.5873 2.4930 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5336 -1.8751 2.8191 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8709 -2.4804 4.0357 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5271 -1.5552 1.9183 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9367 -1.8446 2.2255 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1813 -2.6674 3.1371 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9559 -1.1444 1.4371 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5731 -1.1023 -0.0440 C 0 0 2 0 0 0 0 0 0 0 0 0 4.5408 -0.1856 -0.6952 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4975 1.1824 -0.5672 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4238 2.0083 -1.1939 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4265 1.4721 -1.9727 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3500 2.2993 -2.5973 O 0 0 0 0 0 0 0 0 0 0 0 0 6.4828 0.1029 -2.1105 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5452 -0.7167 -1.4750 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2408 -0.6431 -0.1837 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2349 -0.9590 0.7113 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1049 -0.6911 0.4347 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1125 -1.0519 -0.6505 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.8456 -1.1838 -2.0281 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4989 -0.4572 -0.5439 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8961 -0.4458 0.7881 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5372 0.9476 -1.1429 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.5228 1.6990 -0.5293 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0742 3.3552 -2.0619 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1749 3.3600 -0.5352 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9564 3.5135 -0.4522 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5139 1.1467 -1.7624 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3010 0.0996 -0.7681 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5407 -1.8484 3.2187 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5436 -2.0059 4.8654 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9687 -1.5319 1.5320 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9649 -0.0708 1.7667 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6942 -2.1157 -0.4390 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7030 1.5862 0.0485 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3654 3.0709 -1.0761 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1604 2.5920 -2.0854 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2721 -0.3134 -2.7232 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6584 -1.7824 -1.6335 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3455 -0.2247 -0.5069 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1550 -2.0625 -0.2359 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9013 -1.4681 -2.0958 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1780 -1.1033 -1.1285 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8148 -0.1384 0.8859 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7792 0.8472 -2.2066 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9739 2.2950 -1.1690 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 8 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 18 20 1 0 20 21 2 0 14 22 1 0 22 23 1 0 23 24 2 0 4 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 27 29 1 0 29 30 1 0 29 2 1 0 24 6 1 0 23 10 1 0 21 15 1 0 1 31 1 0 1 32 1 0 1 33 1 0 2 34 1 6 4 35 1 6 7 36 1 0 9 37 1 0 13 38 1 0 13 39 1 0 14 40 1 6 16 41 1 0 17 42 1 0 19 43 1 0 20 44 1 0 21 45 1 0 24 46 1 0 25 47 1 1 26 48 1 0 27 49 1 6 28 50 1 0 29 51 1 6 30 52 1 0 M END

Standard InCHIKey	LUCQSVLCPJUJRN-UHVRHXOTSA-N
Standard InCHI	InChI=1S/C21H22O9/c1-9-18(25)19(26)20(27)21(28-9)29-12-6-13(23)17-14(24)8-15(30-16(17)7-12)10-2-4-11(22)5-3-10/h2-7,9,15,18-23,25-27H,8H2,1H3/t9-,15-,18+,19+,20-,21+/m1/s1
SMILES	C[C@H]1O[C@@H](OC2=CC(O)=C3C(=O)C[C@H](C4=CC=C(O)C=C4)OC3=C2)[C@H](O)[C@@H](O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	418.13	Volume:	398.203 ? Van der Waals volume.
Dense:	1.05	LogP:	1.14 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.491 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.333 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	145.91 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	5.0	Rings:	4.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.493	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.003	Fsp³:	0.381
MCE-18:	87.069 ? 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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.593	Fluc inhibitor:	0.559 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.175 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.487 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.164	Promiscuous compounds:	0.274

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.392	MDCK Permeability:	-5.013
Pgp-inhibitor:	0.238	Pgp-substrate:	0.659
PAMPA:	0.994 ? 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):	0.0
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.688
50% Bioavailability (F50%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.408
Plasma Protein Binding (PPB):	90.913%	Volume Distribution (VD):	-0.053
Fu:	9.295% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.998
BSEP inhibitor:	0.972

ADMET: Metabolism

CYP1A2-inhibitor:	0.09	CYP1A2-substrate:	0.038
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.148
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.295
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.821
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.555
HLM stability:	0.73 ? 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):

2.857

Half-life (T1/2):

3.944

ADMET: Toxicity

hERG Blockers:	0.089	hERG Blockers (10um):	0.424
Human Hepatotoxicity (H-HT):	0.618	Drug-induced Liver Injury (DILI):	0.495
AMES Toxicity:	0.759	Rat Oral Acute Toxicity:	0.104
Maximum Recommended Daily Dose:	0.147	Skin Sensitization:	0.619
Carcinogencity:	0.091	Eye Corrosion:	0.0
Eye Irritation:	0.812	Respiratory Toxicity:	0.011
Drug-induced Neurotoxicity:	0.082	Ototoxicity:	0.902
Hematotoxicity:	0.091	Drug-induced Nephrotoxicity:	0.789
Genotoxicity:	0.582	RPMI-8226 Immunitoxicity:	0.184
A549 Cytotoxicity:	0.412	Hek293 Cytotoxicity:	0.527
BCF:	0.813 ? 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:	3.521 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.86 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.1 ? 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
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1016/S0031-9422(00)88469-1]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/S0031-9422(00)88469-1]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5852	Litsea glutinosa	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5852	Litsea glutinosa	Species	Lauraceae	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 NPC517373 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	13830
0.1-0.2	30252
0.2-0.3	4695
0.3-0.4	875
0.4-0.5	154
0.5-0.6	24
0.6-0.7	14
0.7-0.8	0
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8333	Intermediate Similarity	NPC39351
0.8082	Intermediate Similarity	NPC271270
0.7273	Intermediate Similarity	NPC142860
0.7273	Intermediate Similarity	NPC152538
0.7273	Intermediate Similarity	NPC246469
0.7273	Intermediate Similarity	NPC89088
0.7143	Intermediate Similarity	NPC97052
0.7083	Intermediate Similarity	NPC29830
0.7042	Intermediate Similarity	NPC219163
0.6962	Remote Similarity	NPC43587
0.68	Remote Similarity	NPC236934
0.6463	Remote Similarity	NPC44328
0.6463	Remote Similarity	NPC79056
0.6386	Remote Similarity	NPC293629
0.6349	Remote Similarity	NPC329203
0.6349	Remote Similarity	NPC222342
0.6267	Remote Similarity	NPC206378
0.6265	Remote Similarity	NPC291124
0.6265	Remote Similarity	NPC131157
0.622	Remote Similarity	NPC97285
0.6133	Remote Similarity	NPC26195
0.6081	Remote Similarity	NPC169248
0.6081	Remote Similarity	NPC72649
0.5814	Remote Similarity	NPC105095
0.5814	Remote Similarity	NPC177731
0.5814	Remote Similarity	NPC725
0.5795	Remote Similarity	NPC67134
0.5789	Remote Similarity	NPC170475
0.5783	Remote Similarity	NPC105283
0.5769	Remote Similarity	NPC181014
0.5714	Remote Similarity	NPC471457
0.5532	Remote Similarity	NPC321916
0.5393	Remote Similarity	NPC168789
0.5385	Remote Similarity	NPC163191
0.5303	Remote Similarity	NPC32441
0.5303	Remote Similarity	NPC6407
0.5303	Remote Similarity	NPC79943
0.5303	Remote Similarity	NPC545184
0.5294	Remote Similarity	NPC469764
0.525	Remote Similarity	NPC106625
0.5224	Remote Similarity	NPC150648
0.519	Remote Similarity	NPC308265
0.5147	Remote Similarity	NPC73028
0.5125	Remote Similarity	NPC127782
0.5114	Remote Similarity	NPC472876
0.5072	Remote Similarity	NPC475267
0.507	Remote Similarity	NPC23084

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC517373 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3661
0.1-0.2	5343
0.2-0.3	129
0.3-0.4	12
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
0.6463	Remote Similarity	NPD7074	Phase 3
0.5303	Remote Similarity	NPD1552	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