NPASS Compound

Natural Product: NPC476356

Natural Product ID	NPC476356
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(+)-Lariciresinol-4-O-Beta-D-Glucopyranoside
IUPAC Name	(2R,3R,4R,5S,6R)-5-[4-[(2R,3S,4S)-4-[(4-hydroxy-3-methoxyphenyl)methyl]-3-(hydroxymethyl)oxolan-2-yl]-2-methoxyphenoxy]-6-(hydroxymethyl)oxane-2,3,4-triol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL577378
PubChem CID	45482324
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0003686] Furanoid lignans [CHEMONTID:0001604] Tetrahydrofuran lignans [CHEMONTID:0003422] 7,9'-epoxylignans

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 71 74 0 0 0 0 0 0 0 0999 V2000 2.8630 -0.8601 -2.6360 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2113 0.2675 -2.1905 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0437 0.3545 -0.7138 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3230 0.3622 0.0732 C 0 0 1 0 0 0 0 0 0 0 0 0 2.9130 -0.2863 1.3457 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7684 -1.0392 1.1300 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3176 -0.8395 -0.1456 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1569 -0.6881 -0.2397 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8504 0.1246 0.6322 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2288 0.2285 0.5016 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9548 -0.4380 -0.4567 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2404 -1.2455 -1.3183 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8715 -1.3655 -1.2091 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8955 -1.9464 -2.3054 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2251 -2.7896 -3.2186 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3200 -0.3655 -0.6228 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2371 0.3734 0.1099 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.3380 -0.4825 0.7148 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.8839 -1.1772 1.9744 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9461 -1.9642 2.4178 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4371 0.2963 0.9901 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1602 1.5927 1.3508 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.5871 2.3951 0.1850 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.9833 1.3924 -0.7655 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1865 1.9454 -1.7273 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.5847 3.1632 -0.4321 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3599 1.7153 2.4781 O 0 0 0 0 0 0 0 0 0 0 0 0 4.4509 -0.3230 -0.6173 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7025 -0.3057 0.1711 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0602 -1.3447 0.9735 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2297 -1.2878 1.7083 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0566 -0.1794 1.6426 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6797 0.8675 0.8229 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5192 0.8164 0.0912 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5324 1.9627 0.7822 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2634 3.1007 -0.0143 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2322 -0.1429 2.3918 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1579 -0.7061 -3.5703 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1795 0.2312 -2.6413 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6530 1.2092 -2.5759 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4338 1.2620 -0.4948 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5680 1.4620 0.2213 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6255 0.5153 2.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6655 -0.9664 1.7844 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6290 -1.7244 -0.7531 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2939 0.6487 1.3817 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7214 0.8642 1.1918 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3348 -2.0139 -1.9077 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4655 -2.1429 -3.7358 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9477 -3.1477 -3.9623 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7236 -3.6507 -2.7089 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7056 0.9573 0.8787 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6206 -1.2247 -0.0588 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5456 -0.4912 2.7469 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0885 -1.9085 1.6511 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7008 -1.3681 2.7216 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1406 2.0766 1.5968 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7512 3.0335 0.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8446 0.8618 -1.2512 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6480 1.9388 -2.5835 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2463 2.5065 -0.7714 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9450 1.6911 3.2743 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1918 -1.3916 -0.8060 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7004 0.1218 -1.6033 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4799 -2.2393 1.0671 H 0 0 0 0 0 0 0 0 0 0 0 0 7.5196 -2.1219 2.3551 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2583 1.6650 -0.5425 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9207 3.9264 0.3526 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5696 2.8268 -1.0645 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2102 3.3900 0.0104 H 0 0 0 0 0 0 0 0 0 0 0 0 9.2412 -0.5854 3.2781 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 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 11 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 18 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 23 26 1 0 22 27 1 0 4 28 1 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 33 35 1 0 35 36 1 0 32 37 1 0 7 3 1 0 13 8 1 0 24 17 1 0 34 29 1 0 1 38 1 0 2 39 1 0 2 40 1 0 3 41 1 6 4 42 1 1 5 43 1 0 5 44 1 0 7 45 1 6 9 46 1 0 10 47 1 0 13 48 1 0 15 49 1 0 15 50 1 0 15 51 1 0 17 52 1 1 18 53 1 6 19 54 1 0 19 55 1 0 20 56 1 0 22 57 1 1 23 58 1 1 24 59 1 6 25 60 1 0 26 61 1 0 27 62 1 0 28 63 1 0 28 64 1 0 30 65 1 0 31 66 1 0 34 67 1 0 36 68 1 0 36 69 1 0 36 70 1 0 37 71 1 0 M END

Standard InCHIKey	HLMUYOCDACORAV-NAHKDHJCSA-N
Standard InCHI	InChI=1S/C26H34O11/c1-33-19-8-13(3-5-17(19)29)7-15-12-35-24(16(15)10-27)14-4-6-18(20(9-14)34-2)36-25-21(11-28)37-26(32)23(31)22(25)30/h3-6,8-9,15-16,21-32H,7,10-12H2,1-2H3/t15-,16-,21-,22-,23-,24+,25-,26-/m1/s1
SMILES	OC[C@@H]1[C@@H](CO[C@H]1c1ccc(c(c1)OC)O[C@@H]1[C@@H](CO)O[C@H]([C@@H]([C@H]1O)O)O)Cc1ccc(c(c1)OC)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	522.21	Volume:	504.9 ? Van der Waals volume.
Dense:	1.034	LogP:	0.133 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.72 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.098 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	23.0
TPSA:	167.53 ? 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:	0.265	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.455	Fsp³:	0.538
MCE-18:	89.7 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.531	Fluc inhibitor:	0.289 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.076 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.116 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.088	Promiscuous compounds:	0.097

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.635	MDCK Permeability:	-5.141
Pgp-inhibitor:	0.019	Pgp-substrate:	0.543
PAMPA:	0.185 ? 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):	0.006
20% Bioavailability (F20%):	0.271	30% Bioavailability (F30%):	0.819
50% Bioavailability (F50%):	0.893

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.028	MRP1:	0.301
Plasma Protein Binding (PPB):	74.645%	Volume Distribution (VD):	-0.273
Fu:	24.586% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.94	BCRP inhibitor:	0.047
BSEP inhibitor:	0.679

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.024	CYP2C19-substrate:	0.004
CYP2C9-inhibitor:	0.532	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.194
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.994
HLM stability:	0.029 ? 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):

2.655

Half-life (T1/2):

2.73

ADMET: Toxicity

hERG Blockers:	0.026	hERG Blockers (10um):	0.094
Human Hepatotoxicity (H-HT):	0.887	Drug-induced Liver Injury (DILI):	0.96
AMES Toxicity:	0.977	Rat Oral Acute Toxicity:	0.059
Maximum Recommended Daily Dose:	0.028	Skin Sensitization:	1.0
Carcinogencity:	0.372	Eye Corrosion:	0.0
Eye Irritation:	0.247	Respiratory Toxicity:	0.067
Drug-induced Neurotoxicity:	0.14	Ototoxicity:	0.952
Hematotoxicity:	0.725	Drug-induced Nephrotoxicity:	0.837
Genotoxicity:	0.906	RPMI-8226 Immunitoxicity:	0.212
A549 Cytotoxicity:	0.942	Hek293 Cytotoxicity:	0.609
BCF:	0.708 ? 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:	3.236 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.823 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.91 ? 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
NPO12339	Daphne feddei	Species	Thymelaeaceae	Eukaryota	stem bark	Kunming, Yunnan Province, China	n.a.	PMID[18986199]
NPO12339	Daphne feddei	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12339	Daphne feddei	Species	Thymelaeaceae	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
IC50	1

Activity Type	# Activity
Cell line	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
NPT113	Cell line	RAW264.7	Mus musculus	IC50	>	300000.0	nM	PubChem BioAssay data set

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 NPC476356 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	17029
0.1-0.2	29724
0.2-0.3	2697
0.3-0.4	297
0.4-0.5	98
0.5-0.6	8
0.6-0.7	4
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
0.7222	Intermediate Similarity	NPC64201
0.6588	Remote Similarity	NPC185307
0.6301	Remote Similarity	NPC187998
0.6301	Remote Similarity	NPC257582
0.6301	Remote Similarity	NPC241522
0.5974	Remote Similarity	NPC42300
0.5921	Remote Similarity	NPC486558
0.5843	Remote Similarity	NPC470950
0.5714	Remote Similarity	NPC282833
0.5676	Remote Similarity	NPC206882
0.5402	Remote Similarity	NPC471063
0.5109	Remote Similarity	NPC39657
0.5062	Remote Similarity	NPC67247

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476356 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3979
0.1-0.2	5037
0.2-0.3	130
0.3-0.4	4
0.4-0.5	0
0.5-0.6	0
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
		NPD

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