NPASS Compound

Natural Product: NPC17837

Natural Product ID	NPC17837
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Perrottetin E 11'-Methyl Ether
IUPAC Name	2-[4-[2-(3-hydroxyphenyl)ethyl]phenoxy]-4-[2-(3-methoxyphenyl)ethyl]phenol
Synonyms	Perrottetin E 11'-Methyl Ether; Perrottetin E-11'-Methyl Ether
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL458919
PubChem CID	14841123
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related 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 61 64 0 0 0 0 0 0 0 0999 V2000 -9.8695 1.9619 0.6455 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0129 1.6103 -0.4297 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9256 0.7793 -0.2541 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6594 0.2741 0.9970 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5595 -0.5629 1.1601 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7489 -0.8841 0.0967 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0299 -0.3691 -1.1511 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1574 -0.7148 -2.2967 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0338 0.3003 -2.4102 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1933 0.3369 -1.1843 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5042 1.1956 -0.1334 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7218 1.2226 0.9952 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6255 0.3956 1.0851 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3227 -0.4469 0.0508 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0977 -0.4863 -1.0888 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2321 -1.2999 0.0880 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0814 -0.9756 0.2156 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7723 -0.6175 -0.9508 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1070 -0.2721 -0.9323 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8294 -0.2628 0.2422 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2685 0.1038 0.3023 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1368 -1.1190 0.1170 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5557 -0.6986 0.1852 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2186 -0.6819 1.3949 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5475 -0.2897 1.4684 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2475 0.0975 0.3219 C 0 0 0 0 0 0 0 0 0 0 0 0 9.5889 0.0811 -0.8814 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2726 -0.3113 -0.9283 C 0 0 0 0 0 0 0 0 0 0 0 0 10.2962 0.4701 -2.0248 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1630 -0.6128 1.3960 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8073 -0.9649 1.3843 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8208 0.4269 2.2520 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1214 0.4625 -1.3170 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.3100 2.4888 1.4417 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.7095 2.5679 0.2810 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.2309 0.9874 1.0696 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2531 0.4844 1.8760 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3043 -0.9882 2.1234 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8784 -1.5403 0.2007 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7765 -1.7349 -2.1372 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6897 -0.7055 -3.2588 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5113 1.3116 -2.4809 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4393 0.1316 -3.3304 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3727 1.8330 -0.2352 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9631 1.8909 1.8143 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8460 -1.1706 -1.9210 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2282 -0.6146 -1.9004 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6403 0.0057 -1.8411 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4822 0.7733 -0.5799 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4812 0.6515 1.2216 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8903 -1.8191 0.9564 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9158 -1.5778 -0.8477 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7112 -0.9740 2.3006 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0362 -0.2875 2.4266 H 0 0 0 0 0 0 0 0 0 0 0 0 11.2909 0.4058 0.3773 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7719 -0.3197 -1.8699 H 0 0 0 0 0 0 0 0 0 0 0 0 10.2724 -0.2159 -2.7887 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6918 -0.6186 2.3385 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2976 -1.2452 2.2927 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3310 1.2609 2.5266 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3507 0.8709 -2.2874 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 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 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 27 29 1 0 20 30 1 0 30 31 2 0 13 32 1 0 7 33 2 0 33 3 1 0 15 10 1 0 31 17 1 0 28 23 1 0 1 34 1 0 1 35 1 0 1 36 1 0 4 37 1 0 5 38 1 0 6 39 1 0 8 40 1 0 8 41 1 0 9 42 1 0 9 43 1 0 11 44 1 0 12 45 1 0 15 46 1 0 18 47 1 0 19 48 1 0 21 49 1 0 21 50 1 0 22 51 1 0 22 52 1 0 24 53 1 0 25 54 1 0 26 55 1 0 28 56 1 0 29 57 1 0 30 58 1 0 31 59 1 0 32 60 1 0 33 61 1 0 M END

Standard InCHIKey	NZWFFDGHEUMZNF-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C29H28O4/c1-32-27-7-3-5-23(19-27)10-11-24-14-17-28(31)29(20-24)33-26-15-12-21(13-16-26)8-9-22-4-2-6-25(30)18-22/h2-7,12-20,30-31H,8-11H2,1H3
SMILES	COc1cccc(CCc2ccc(c(c2)Oc2ccc(CCc3cccc(c3)O)cc2)O)c1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	440.2	Volume:	479.438 ? Van der Waals volume.
Dense:	0.918	LogP:	5.906 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.42 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.308 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	24.0
TPSA:	58.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.313	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.141	Fsp³:	0.172
MCE-18:	21.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	1.0	Fluc inhibitor:	0.597 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.059 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.797 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.625	Promiscuous compounds:	0.098

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.036	MDCK Permeability:	-4.781
Pgp-inhibitor:	0.991	Pgp-substrate:	0.015
PAMPA:	0.008 ? 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):	0.143
20% Bioavailability (F20%):	0.957	30% Bioavailability (F30%):	0.954
50% Bioavailability (F50%):	0.967

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003	MRP1:	0.038
Plasma Protein Binding (PPB):	98.906%	Volume Distribution (VD):	0.278
Fu:	0.444% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.982
OATP1B3 inhibitor:	0.847	BCRP inhibitor:	0.268
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.977	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.985	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.8
CYP2D6-inhibitor:	0.991	CYP2D6-substrate:	0.996
CYP3A4-inhibitor:	0.985	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.354	CYP2C8-inhibitor:	1.0
HLM stability:	0.998 ? 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):

9.791

Half-life (T1/2):

0.555

ADMET: Toxicity

hERG Blockers:	0.948	hERG Blockers (10um):	0.967
Human Hepatotoxicity (H-HT):	0.729	Drug-induced Liver Injury (DILI):	0.159
AMES Toxicity:	0.624	Rat Oral Acute Toxicity:	0.057
Maximum Recommended Daily Dose:	0.771	Skin Sensitization:	0.803
Carcinogencity:	0.13	Eye Corrosion:	0.001
Eye Irritation:	0.545	Respiratory Toxicity:	0.391
Drug-induced Neurotoxicity:	0.388	Ototoxicity:	0.808
Hematotoxicity:	0.236	Drug-induced Nephrotoxicity:	0.726
Genotoxicity:	0.155	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.917	Hek293 Cytotoxicity:	0.962
BCF:	2.003 ? 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:	5.411 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.275 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.899 ? 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
NPO33046	liverworts	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[16378374]
NPO33046	liverworts	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[21652215]
NPO33046	liverworts	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]

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	=	49850.0	nM	PMID[22104973]

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 NPC17837 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	25539
0.1-0.2	20075
0.2-0.3	3862
0.3-0.4	294
0.4-0.5	59
0.5-0.6	14
0.6-0.7	10
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8542	High Similarity	NPC5948
0.7037	Intermediate Similarity	NPC599909
0.7037	Intermediate Similarity	NPC604545
0.6557	Remote Similarity	NPC599974
0.65	Remote Similarity	NPC226193
0.65	Remote Similarity	NPC601081
0.6393	Remote Similarity	NPC606874
0.6379	Remote Similarity	NPC474134
0.6364	Remote Similarity	NPC131128
0.625	Remote Similarity	NPC601376
0.62	Remote Similarity	NPC75440
0.6094	Remote Similarity	NPC141023
0.6	Remote Similarity	NPC601463
0.5902	Remote Similarity	NPC134431
0.5902	Remote Similarity	NPC156854
0.5873	Remote Similarity	NPC73656
0.5781	Remote Similarity	NPC606516
0.5769	Remote Similarity	NPC86947
0.5738	Remote Similarity	NPC304630
0.5714	Remote Similarity	NPC483726
0.5714	Remote Similarity	NPC610261
0.566	Remote Similarity	NPC53906
0.5522	Remote Similarity	NPC474390
0.5522	Remote Similarity	NPC210655
0.5472	Remote Similarity	NPC22610
0.5469	Remote Similarity	NPC483725
0.52	Remote Similarity	NPC233599

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC17837 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4152
0.1-0.2	4751
0.2-0.3	241
0.3-0.4	6
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