NPASS Compound

Natural Product: NPC237594

Natural Product ID	NPC237594
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Erythro-(7S,8R)-Guaiacylglycerol-B-Coniferyl Aldehyde Ether
IUPAC Name	(E)-3-[4-[(1S,2R)-1,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)propan-2-yl]oxy-3-methoxyphenyl]prop-2-enal
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2430312
PubChem CID	73350868
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 49 50 0 0 0 0 0 0 0 0999 V2000 -3.6379 2.0232 2.9450 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6857 1.1766 2.5828 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5362 0.1251 1.6841 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2756 -0.0722 1.1342 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0505 -1.0878 0.2418 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1276 -1.9216 -0.1012 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3741 -1.7271 0.4418 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5821 -0.7013 1.3377 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8567 -0.4993 1.8957 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7419 -1.3524 -0.3634 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5628 -0.8278 0.4260 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4671 -1.4924 1.7879 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3366 -2.8725 1.6821 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6116 -1.1434 -0.2642 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5931 -0.2906 -0.6897 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5372 1.0652 -0.4752 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5411 1.9449 -0.9094 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6260 1.4323 -1.5769 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6993 2.2902 -2.0523 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7517 3.5811 -1.9063 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8862 4.3581 -2.4264 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9458 5.5980 -2.2912 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6751 0.0778 -1.7875 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7089 -0.7981 -1.3735 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7628 -2.1693 -1.5890 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8907 -2.6763 -2.2795 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5642 -2.7419 -0.4278 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2293 2.5294 2.0447 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8068 1.4193 3.3721 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9882 2.7774 3.6537 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4605 0.5809 1.4020 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9671 -2.7373 -0.8121 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1949 -2.3705 0.1740 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0173 0.2977 2.4835 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7210 -0.9702 -1.4035 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6317 0.2525 0.6104 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4151 -1.0586 2.2991 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3666 -1.2807 2.3566 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2185 -3.2684 2.3916 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7183 1.5525 0.0422 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4313 3.0087 -0.7047 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5571 1.8424 -2.5859 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9696 4.0945 -1.4056 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7030 3.8711 -2.9426 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5292 -0.3485 -2.3160 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0131 -2.1022 -3.2226 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7977 -2.5036 -1.6762 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7557 -3.7334 -2.5801 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1560 -3.1514 0.2490 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 2 0 8 9 1 0 5 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 11 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 18 23 1 0 23 24 2 0 24 25 1 0 25 26 1 0 10 27 1 0 8 3 1 0 24 15 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 6 32 1 0 7 33 1 0 9 34 1 0 10 35 1 6 11 36 1 1 12 37 1 0 12 38 1 0 13 39 1 0 16 40 1 0 17 41 1 0 19 42 1 0 20 43 1 0 21 44 1 0 23 45 1 0 26 46 1 0 26 47 1 0 26 48 1 0 27 49 1 0 M END

Standard InCHIKey	LWLOALZBDOVWAE-WGLWSTOQSA-N
Standard InCHI	InChI=1S/C20H22O7/c1-25-17-11-14(6-7-15(17)23)20(24)19(12-22)27-16-8-5-13(4-3-9-21)10-18(16)26-2/h3-11,19-20,22-24H,12H2,1-2H3/b4-3+/t19-,20+/m1/s1
SMILES	COc1cc(ccc1O)[C@@H]([C@@H](CO)Oc1ccc(/C=C/C=O)cc1OC)O

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	fruit	n.a.	PMID[15739361]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	seed	n.a.	PMID[23845552]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	seeds	n.a.	n.a.	PMID[23999046]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12011	Crataegus pinnatifida	Species	Rosaceae	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	12

Activity Type	# Activity
Cell line	10
Non-molecular	2

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
NPT171	Cell line	MRC5	Homo sapiens	IC50	>	50000.0	nM	PMID[15043429]
NPT111	Cell line	K562	Homo sapiens	IC50	>	50000.0	nM	PMID[10780915]
NPT466	Cell line	U-937	Homo sapiens	IC50	>	50000.0	nM	PubChem BioAssay data set
NPT116	Cell line	HL-60	Homo sapiens	IC50	=	36550.0	nM	PMID[21130542]
NPT453	Cell line	HT-1080	Homo sapiens	IC50	=	35220.0	nM	PMID[18672931]
NPT81	Cell line	A549	Homo sapiens	IC50	=	33650.0	nM	PMID[25938459]
NPT393	Cell line	HCT-116	Homo sapiens	IC50	=	32450.0	nM	PMID[25856683]
NPT65	Cell line	HepG2	Homo sapiens	IC50	=	38540.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	50000.0	nM	Open TG-GATES in vivo data: Biochemistry
NPT165	Cell line	HeLa	Homo sapiens	IC50	>	50000.0	nM	PMID[2016726]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	36440.0	nM	PMID[23999046]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	929.0	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 NPC237594 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	21962
0.1-0.2	23631
0.2-0.3	3570
0.3-0.4	555
0.4-0.5	92
0.5-0.6	19
0.6-0.7	16
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC476387
1.0	High Similarity	NPC119060
0.8393	Intermediate Similarity	NPC147821
0.8393	Intermediate Similarity	NPC319625
0.8393	Intermediate Similarity	NPC183181
0.8393	Intermediate Similarity	NPC41706
0.807	Intermediate Similarity	NPC267291
0.6949	Remote Similarity	NPC58607
0.6949	Remote Similarity	NPC191037
0.6949	Remote Similarity	NPC178284
0.6897	Remote Similarity	NPC9370
0.6897	Remote Similarity	NPC287495
0.6774	Remote Similarity	NPC249791
0.6667	Remote Similarity	NPC114901
0.6667	Remote Similarity	NPC48990
0.6667	Remote Similarity	NPC601893
0.6557	Remote Similarity	NPC7903
0.6557	Remote Similarity	NPC160991
0.6494	Remote Similarity	NPC470827
0.6452	Remote Similarity	NPC111247
0.6452	Remote Similarity	NPC292056
0.6438	Remote Similarity	NPC470413
0.6133	Remote Similarity	NPC470769
0.5974	Remote Similarity	NPC470828
0.5833	Remote Similarity	NPC310854
0.5741	Remote Similarity	NPC39793
0.5672	Remote Similarity	NPC224876
0.5672	Remote Similarity	NPC472969
0.5606	Remote Similarity	NPC481839
0.5479	Remote Similarity	NPC114119
0.5479	Remote Similarity	NPC471415
0.5455	Remote Similarity	NPC83375
0.5441	Remote Similarity	NPC118787
0.5395	Remote Similarity	NPC107145
0.5385	Remote Similarity	NPC16208
0.5325	Remote Similarity	NPC473909
0.5224	Remote Similarity	NPC163332
0.5224	Remote Similarity	NPC75695
0.5152	Remote Similarity	NPC214729
0.5152	Remote Similarity	NPC479110
0.5094	Remote Similarity	NPC179309
0.5063	Remote Similarity	NPC260397

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC237594 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4269
0.1-0.2	4703
0.2-0.3	164
0.3-0.4	13
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