NPASS Compound

Natural Product: NPC26195

Natural Product ID	NPC26195
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Naringenin 4'-O-Beta-D-Glucopyranoside
IUPAC Name	(2S)-5,7-dihydroxy-2-[4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]-2,3-dihydrochromen-4-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL453552
PubChem CID	157745
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid 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 53 56 0 0 0 0 0 0 0 0999 V2000 1.2658 -0.5948 0.8980 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0764 -0.7252 1.1833 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0387 -0.3032 0.2920 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5943 0.2501 -0.8870 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7458 0.3837 -1.1790 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7045 -0.0378 -0.2887 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1192 0.1208 -0.6382 C 0 0 2 0 0 0 0 0 0 0 0 0 3.6225 -1.1639 -1.1997 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9961 -1.5084 -0.7272 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4549 -2.6735 -0.8885 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8688 -0.5457 -0.0681 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2296 -0.6463 0.0063 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0065 0.3071 0.6505 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4109 1.3998 1.2421 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0375 1.4995 1.1660 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2548 0.5506 0.5239 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8931 0.6262 0.4346 O 0 0 0 0 0 0 0 0 0 0 0 0 8.1649 2.3839 1.9023 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8137 -1.7709 -0.6054 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3488 -0.4608 0.6347 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4814 -0.1136 -0.0965 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3157 -1.3884 -0.2583 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.6255 -1.1719 0.4617 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.2964 0.0226 -0.2292 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.3778 1.2007 -0.0159 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.1092 2.1763 0.8857 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3225 2.5889 0.3098 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2003 0.8552 0.6377 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4500 -0.3151 -1.5602 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3264 -0.7233 1.7633 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5319 -1.5984 -1.6248 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0506 -0.9214 1.5877 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3666 -1.1676 2.1256 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3444 0.5884 -1.6016 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0388 0.8321 -2.1341 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1970 0.8959 -1.4377 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9617 -2.0280 -0.8966 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6866 -1.1227 -2.3219 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0694 0.2163 0.7013 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5506 2.3475 1.6226 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1352 2.5238 1.5822 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6879 -2.6927 -0.1648 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2924 0.3506 -1.0817 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8244 -2.2642 0.1792 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2677 -2.0530 0.4529 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2974 0.1678 0.2298 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2115 1.7010 -0.9765 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5202 3.0991 1.0622 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3339 1.7436 1.8689 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2485 2.6874 -0.6733 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0364 0.3669 -2.1341 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5951 -1.3187 2.0805 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5327 -2.5765 -1.7757 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 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 2 0 14 15 1 0 15 16 2 0 16 17 1 0 14 18 1 0 12 19 1 0 3 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 25 28 1 0 24 29 1 0 23 30 1 0 22 31 1 0 6 1 1 0 17 7 1 0 28 21 1 0 16 11 1 0 1 32 1 0 2 33 1 0 4 34 1 0 5 35 1 0 7 36 1 6 8 37 1 0 8 38 1 0 13 39 1 0 15 40 1 0 18 41 1 0 19 42 1 0 21 43 1 6 22 44 1 1 23 45 1 1 24 46 1 1 25 47 1 6 26 48 1 0 26 49 1 0 27 50 1 0 29 51 1 0 30 52 1 0 31 53 1 0 M END

Standard InCHIKey	KSDSYIXRWHRPMN-SFTVRKLSSA-N
Standard InCHI	InChI=1S/C21H22O10/c22-8-16-18(26)19(27)20(28)21(31-16)29-11-3-1-9(2-4-11)14-7-13(25)17-12(24)5-10(23)6-15(17)30-14/h1-6,14,16,18-24,26-28H,7-8H2/t14-,16+,18+,19-,20+,21+/m0/s1
SMILES	c1cc(ccc1[C@@H]1CC(=O)c2c(cc(cc2O1)O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.12	Volume:	406.993 ? Van der Waals volume.
Dense:	1.067	LogP:	1.03 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.428 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.185 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	166.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	4.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.385	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.975	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:	0.628	Fluc inhibitor:	0.572 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.126 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.423 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.226	Promiscuous compounds:	0.316

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.671	MDCK Permeability:	-5.031
Pgp-inhibitor:	0.134	Pgp-substrate:	0.144
PAMPA:	0.942 ? 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):	0.322
20% Bioavailability (F20%):	0.003	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.139
Plasma Protein Binding (PPB):	92.92%	Volume Distribution (VD):	-0.234
Fu:	6.76% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.971
BSEP inhibitor:	0.028

ADMET: Metabolism

CYP1A2-inhibitor:	0.154	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.014
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.162
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.802
HLM stability:	0.184 ? 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):

3.047

Half-life (T1/2):

3.151

ADMET: Toxicity

hERG Blockers:	0.036	hERG Blockers (10um):	0.13
Human Hepatotoxicity (H-HT):	0.816	Drug-induced Liver Injury (DILI):	0.963
AMES Toxicity:	0.964	Rat Oral Acute Toxicity:	0.068
Maximum Recommended Daily Dose:	0.087	Skin Sensitization:	0.983
Carcinogencity:	0.462	Eye Corrosion:	0.0
Eye Irritation:	0.589	Respiratory Toxicity:	0.03
Drug-induced Neurotoxicity:	0.026	Ototoxicity:	0.901
Hematotoxicity:	0.233	Drug-induced Nephrotoxicity:	0.8
Genotoxicity:	0.983	RPMI-8226 Immunitoxicity:	0.166
A549 Cytotoxicity:	0.623	Hek293 Cytotoxicity:	0.634
BCF:	0.591 ? 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:	3.279 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.924 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.992 ? 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
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11087602]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12932124]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	stem	n.a.	PMID[12932124]
NPO27239	Maclura tinctoria	Species	Moraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27239	Maclura tinctoria	Species	Moraceae	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

Activity Type	# Activity
Activity	1

Activity Type	# Activity
Non-molecular	1

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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	Activity	=	0.782	mM	PMID[12932124]

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 NPC26195 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	18407
0.1-0.2	26551
0.2-0.3	3617
0.3-0.4	931
0.4-0.5	276
0.5-0.6	52
0.6-0.7	16
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
0.7681	Intermediate Similarity	NPC219163
0.7536	Intermediate Similarity	NPC170475
0.7429	Intermediate Similarity	NPC39351
0.7286	Intermediate Similarity	NPC97052
0.6757	Remote Similarity	NPC29830
0.6667	Remote Similarity	NPC169248
0.6667	Remote Similarity	NPC72649
0.6627	Remote Similarity	NPC168789
0.6618	Remote Similarity	NPC199335
0.6533	Remote Similarity	NPC181014
0.6522	Remote Similarity	NPC190217
0.6494	Remote Similarity	NPC236934
0.6377	Remote Similarity	NPC477240
0.625	Remote Similarity	NPC274784
0.625	Remote Similarity	NPC20709
0.6234	Remote Similarity	NPC5778
0.6184	Remote Similarity	NPC206378
0.6133	Remote Similarity	NPC259182
0.6087	Remote Similarity	NPC106025
0.6053	Remote Similarity	NPC471457
0.5974	Remote Similarity	NPC257963
0.5814	Remote Similarity	NPC70441
0.5692	Remote Similarity	NPC32441
0.5692	Remote Similarity	NPC243083
0.5692	Remote Similarity	NPC13768
0.5692	Remote Similarity	NPC287246
0.5692	Remote Similarity	NPC79943
0.5581	Remote Similarity	NPC97285
0.5556	Remote Similarity	NPC472383
0.5513	Remote Similarity	NPC88484
0.5402	Remote Similarity	NPC142860
0.5402	Remote Similarity	NPC152538
0.5402	Remote Similarity	NPC246469
0.5402	Remote Similarity	NPC89088
0.5385	Remote Similarity	NPC160156
0.5385	Remote Similarity	NPC92565
0.5385	Remote Similarity	NPC199079
0.5366	Remote Similarity	NPC472381
0.5366	Remote Similarity	NPC477502
0.5349	Remote Similarity	NPC105283
0.5316	Remote Similarity	NPC45400
0.5303	Remote Similarity	NPC182421
0.5301	Remote Similarity	NPC479540
0.5287	Remote Similarity	NPC271270
0.5286	Remote Similarity	NPC302950
0.5263	Remote Similarity	NPC121001
0.5217	Remote Similarity	NPC321011
0.5217	Remote Similarity	NPC294852
0.5217	Remote Similarity	NPC214454
0.5217	Remote Similarity	NPC188679
0.5211	Remote Similarity	NPC23084
0.5195	Remote Similarity	NPC475790
0.5185	Remote Similarity	NPC106625
0.5155	Remote Similarity	NPC321916
0.5152	Remote Similarity	NPC294470
0.5139	Remote Similarity	NPC26080
0.5139	Remote Similarity	NPC165686
0.5139	Remote Similarity	NPC236637
0.5135	Remote Similarity	NPC477841
0.5132	Remote Similarity	NPC174953
0.5132	Remote Similarity	NPC479374
0.5128	Remote Similarity	NPC259767
0.5125	Remote Similarity	NPC163191
0.5125	Remote Similarity	NPC603902
0.5077	Remote Similarity	NPC212729
0.5077	Remote Similarity	NPC142319
0.5077	Remote Similarity	NPC604498
0.5072	Remote Similarity	NPC338131
0.506	Remote Similarity	NPC300537
0.5055	Remote Similarity	NPC105095
0.5055	Remote Similarity	NPC177731
0.5055	Remote Similarity	NPC725

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC26195 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4421
0.1-0.2	4610
0.2-0.3	97
0.3-0.4	14
0.4-0.5	5
0.5-0.6	3
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
0.5692	Remote Similarity	NPD1550	Phase 2
0.5692	Remote Similarity	NPD1552	Clinical (unspecified phase)
0.5286	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