NPASS Compound

Natural Product: NPC160991

Natural Product ID	NPC160991
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(+)-Threo-Guaiacylglycerol-Beta-O-4'-Sinapyl Ether
IUPAC Name	(1R,2R)-1-(4-hydroxy-3-methoxyphenyl)-2-[4-[(E)-3-hydroxyprop-1-enyl]-2,6-dimethoxyphenoxy]propane-1,3-diol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2268766
PubChem CID	76326750
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 55 56 0 0 0 0 0 0 0 0999 V2000 -5.0973 5.1409 0.5901 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3088 4.2028 -0.3991 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3696 3.0256 -0.2657 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5394 2.7239 -1.2327 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5927 1.6267 -1.2317 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7847 1.3974 -2.3543 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8821 0.3554 -2.3750 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1280 0.2167 -3.5393 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.2451 1.0580 -4.6425 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7341 -0.5021 -1.2986 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5268 -0.2724 -0.2041 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4447 0.7752 -0.1656 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4475 -1.0791 0.9111 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2742 -0.8273 2.0187 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1563 -1.5041 -1.3649 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5042 -1.6116 -1.1665 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0411 -2.5405 -0.1474 C 0 0 1 0 0 0 0 0 0 0 0 0 2.0937 -2.0548 1.2426 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1458 -2.3989 2.1636 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1831 -1.9503 3.4819 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2104 -1.1285 3.8750 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1880 -0.7520 2.9904 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1275 -1.2142 1.6818 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1814 0.0736 3.4666 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2283 0.5062 2.6238 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1972 -0.7079 5.2094 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6669 -3.8724 -0.2841 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2815 -1.8346 -2.4701 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8927 -2.9860 -3.1078 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3323 4.6990 1.4652 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3360 3.7953 -0.3193 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1855 4.6496 -1.4260 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3718 2.4260 0.6201 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5685 3.3612 -2.1193 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9063 2.0682 -3.1914 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1398 0.9385 -5.2549 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2179 2.1314 -4.3067 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6423 0.9244 -5.3301 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0619 0.9381 0.7028 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0725 0.2196 2.3546 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3353 -0.8438 1.6372 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1202 -1.5609 2.8431 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8615 -0.5732 -0.8490 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1803 -2.6001 -0.4180 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3264 -3.0398 1.8858 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4026 -2.2521 4.1776 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9075 -0.9133 0.9871 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7365 1.3986 3.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8616 0.7721 1.6000 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0202 -0.2755 2.5214 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3943 0.2794 5.3743 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9040 -4.1455 0.2619 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3430 -2.0097 -2.1374 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3238 -0.9318 -3.0924 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0212 -3.3215 -2.7456 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 7 10 2 0 10 11 1 0 11 12 2 0 11 13 1 0 13 14 1 0 10 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 21 26 1 0 17 27 1 0 16 28 1 0 28 29 1 0 12 5 1 0 23 18 1 0 1 30 1 0 2 31 1 0 2 32 1 0 3 33 1 0 4 34 1 0 6 35 1 0 9 36 1 0 9 37 1 0 9 38 1 0 12 39 1 0 14 40 1 0 14 41 1 0 14 42 1 0 16 43 1 1 17 44 1 6 19 45 1 0 20 46 1 0 23 47 1 0 25 48 1 0 25 49 1 0 25 50 1 0 26 51 1 0 27 52 1 0 28 53 1 0 28 54 1 0 29 55 1 0 M END

Standard InCHIKey	JVQPMSYMHZSFNV-WEPWYQGCSA-N
Standard InCHI	InChI=1S/C21H26O8/c1-26-16-11-14(6-7-15(16)24)20(25)19(12-23)29-21-17(27-2)9-13(5-4-8-22)10-18(21)28-3/h4-7,9-11,19-20,22-25H,8,12H2,1-3H3/b5-4+/t19-,20-/m1/s1
SMILES	OC/C=C/c1cc(OC)c(c(c1)OC)O[C@@H]([C@@H](c1ccc(c(c1)OC)O)O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	406.16	Volume:	406.526 ? Van der Waals volume.
Dense:	0.999	LogP:	1.072 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.4 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.925 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	13.0
TPSA:	117.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	4.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.473	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.349	Fsp³:	0.333
MCE-18:	30.0 ? 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:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.454	Fluc inhibitor:	0.706 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.069 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.374 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.28	Promiscuous compounds:	0.463

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.157	MDCK Permeability:	-4.933
Pgp-inhibitor:	0.013	Pgp-substrate:	0.031
PAMPA:	0.56 ? 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%):	0.085	30% Bioavailability (F30%):	0.298
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.371
Plasma Protein Binding (PPB):	77.837%	Volume Distribution (VD):	0.098
Fu:	24.923% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.424
BSEP inhibitor:	0.462

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.053	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.07	CYP2C9-substrate:	0.185
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.019	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.792
HLM stability:	0.351 ? 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):

8.44

Half-life (T1/2):

1.732

ADMET: Toxicity

hERG Blockers:	0.084	hERG Blockers (10um):	0.381
Human Hepatotoxicity (H-HT):	0.836	Drug-induced Liver Injury (DILI):	0.183
AMES Toxicity:	0.38	Rat Oral Acute Toxicity:	0.05
Maximum Recommended Daily Dose:	0.277	Skin Sensitization:	0.789
Carcinogencity:	0.177	Eye Corrosion:	0.0
Eye Irritation:	0.486	Respiratory Toxicity:	0.139
Drug-induced Neurotoxicity:	0.422	Ototoxicity:	0.797
Hematotoxicity:	0.133	Drug-induced Nephrotoxicity:	0.613
Genotoxicity:	0.217	RPMI-8226 Immunitoxicity:	0.102
A549 Cytotoxicity:	0.153	Hek293 Cytotoxicity:	0.198
BCF:	0.348 ? 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:	2.795 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.322 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.412 ? 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
NPO9642	Brassica fruticulosa	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14518939]
NPO9642	Brassica fruticulosa	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9642	Brassica fruticulosa	Species	Brassicaceae	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
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.	IC50	=	23530.0	nM	PMID[26774654]

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 NPC160991 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	24823
0.1-0.2	20578
0.2-0.3	3830
0.3-0.4	494
0.4-0.5	84
0.5-0.6	27
0.6-0.7	11
0.7-0.8	0
0.8-0.85	1
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	NPC7903
0.8182	Intermediate Similarity	NPC267291
0.7885	Intermediate Similarity	NPC184447
0.7857	Intermediate Similarity	NPC147821
0.7857	Intermediate Similarity	NPC319625
0.7857	Intermediate Similarity	NPC183181
0.7857	Intermediate Similarity	NPC41706
0.7059	Intermediate Similarity	NPC260397
0.7037	Intermediate Similarity	NPC310854
0.6724	Remote Similarity	NPC16208
0.6557	Remote Similarity	NPC476387
0.6557	Remote Similarity	NPC237594
0.6557	Remote Similarity	NPC119060
0.6393	Remote Similarity	NPC481839
0.623	Remote Similarity	NPC75695
0.6167	Remote Similarity	NPC114901
0.6167	Remote Similarity	NPC48990
0.6094	Remote Similarity	NPC470098
0.6094	Remote Similarity	NPC473266
0.6061	Remote Similarity	NPC470097
0.597	Remote Similarity	NPC470826
0.5946	Remote Similarity	NPC470769
0.5833	Remote Similarity	NPC9370
0.5833	Remote Similarity	NPC287495
0.5789	Remote Similarity	NPC470828
0.5769	Remote Similarity	NPC78918
0.5769	Remote Similarity	NPC139617
0.5645	Remote Similarity	NPC58607
0.5645	Remote Similarity	NPC191037
0.5645	Remote Similarity	NPC178284
0.5645	Remote Similarity	NPC601893
0.55	Remote Similarity	NPC35932
0.55	Remote Similarity	NPC470827
0.5484	Remote Similarity	NPC203831
0.5469	Remote Similarity	NPC111247
0.5469	Remote Similarity	NPC292056
0.5342	Remote Similarity	NPC43065
0.5342	Remote Similarity	NPC473236
0.527	Remote Similarity	NPC324517
0.527	Remote Similarity	NPC321972
0.527	Remote Similarity	NPC469559
0.5238	Remote Similarity	NPC170694
0.5231	Remote Similarity	NPC163332
0.5224	Remote Similarity	NPC224876
0.5224	Remote Similarity	NPC472969
0.52	Remote Similarity	NPC475250
0.5195	Remote Similarity	NPC470413

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC160991 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5040
0.1-0.2	3969
0.2-0.3	130
0.3-0.4	10
0.4-0.5	1
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