NPASS Compound

Natural Product: NPC217472

Natural Product ID	NPC217472
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-Hydroxyethyl 3-(3,4-Dihydroxyphenyl)Acrylate
IUPAC Name	2-hydroxyethyl (E)-3-(3,4-dihydroxyphenyl)prop-2-enoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL252521
PubChem CID	23656804
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic acids and derivatives [CHEMONTID:0000059] Coumaric acids and derivatives

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 28 28 0 0 0 0 0 0 0 0999 V2000 -6.2382 -0.5106 -0.4533 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8964 -0.1808 -0.1643 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2606 -1.2741 0.6605 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9309 -0.9345 0.9425 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9473 -0.7482 -0.0015 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2517 -0.8949 -1.2137 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5648 -0.3853 0.3786 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3564 -0.2126 -0.5345 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7114 0.1414 -0.1899 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1254 0.3199 1.1016 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4359 0.6602 1.4011 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3666 0.8300 0.3995 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9631 0.6527 -0.9154 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6664 0.3167 -1.1986 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9277 0.8308 -1.9160 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6951 1.1723 0.6577 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7195 0.3366 -0.5532 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8952 0.7874 0.3785 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3515 -0.0132 -1.0993 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8249 -1.4377 1.6055 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2349 -2.2293 0.0584 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3637 -0.2747 1.4091 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0935 -0.3404 -1.6007 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4564 0.2055 1.9506 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7683 0.8029 2.4271 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3648 0.1812 -2.2319 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6121 0.0632 -1.9764 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9368 2.1354 0.8614 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 2 0 5 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 13 15 1 0 12 16 1 0 14 9 1 0 1 17 1 0 2 18 1 0 2 19 1 0 3 20 1 0 3 21 1 0 7 22 1 0 8 23 1 0 10 24 1 0 11 25 1 0 14 26 1 0 15 27 1 0 16 28 1 0 M END

Standard InCHIKey	GQMXXQFZDGUTPH-DUXPYHPUSA-N
Standard InCHI	InChI=1S/C11H12O5/c12-5-6-16-11(15)4-2-8-1-3-9(13)10(14)7-8/h1-4,7,12-14H,5-6H2/b4-2+
SMILES	OCCOC(=O)/C=C/c1ccc(c(c1)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	224.07	Volume:	221.025 ? Van der Waals volume.
Dense:	1.014	LogP:	1.313 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.121 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.095 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	8.0
TPSA:	86.99 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	3.0	Rings:	1.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.397	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.201	Fsp³:	0.182
MCE-18:	7.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.608	Fluc inhibitor:	0.976 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.243 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.403 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.876	Promiscuous compounds:	0.96

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.976	MDCK Permeability:	-4.954
Pgp-inhibitor:	0.004	Pgp-substrate:	0.058
PAMPA:	0.771 ? 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):	0.319
20% Bioavailability (F20%):	0.976	30% Bioavailability (F30%):	0.988
50% Bioavailability (F50%):	0.991

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.061	MRP1:	0.126
Plasma Protein Binding (PPB):	65.542%	Volume Distribution (VD):	-0.339
Fu:	31.981% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.958
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.11
BSEP inhibitor:	0.112

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.028
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.014
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.005
CYP2D6-inhibitor:	0.02	CYP2D6-substrate:	0.464
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.843
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.982
HLM stability:	0.155 ? 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):

12.512

Half-life (T1/2):

1.479

ADMET: Toxicity

hERG Blockers:	0.076	hERG Blockers (10um):	0.464
Human Hepatotoxicity (H-HT):	0.287	Drug-induced Liver Injury (DILI):	0.423
AMES Toxicity:	0.455	Rat Oral Acute Toxicity:	0.054
Maximum Recommended Daily Dose:	0.197	Skin Sensitization:	0.998
Carcinogencity:	0.386	Eye Corrosion:	0.506
Eye Irritation:	0.995	Respiratory Toxicity:	0.14
Drug-induced Neurotoxicity:	0.04	Ototoxicity:	0.379
Hematotoxicity:	0.021	Drug-induced Nephrotoxicity:	0.075
Genotoxicity:	0.118	RPMI-8226 Immunitoxicity:	0.016
A549 Cytotoxicity:	0.146	Hek293 Cytotoxicity:	0.161
BCF:	0.783 ? 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:	3.44 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.75 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.441 ? 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
NPO33086	bermuda buttercup	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[17922549]
NPO33086	bermuda buttercup	Species	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
Activity	5

Activity Type	# Activity
Organism	5

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
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	10.0	%	PMID[10425085]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	>=	80.0	%	PMID[10201823]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	100.0	%	PMID[22264489]
NPT364	Organism	Lactuca sativa	Lactuca sativa	Activity	=	60.0	%	PMID[22264489]

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 NPC217472 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	14877
0.1-0.2	30595
0.2-0.3	3677
0.3-0.4	483
0.4-0.5	163
0.5-0.6	40
0.6-0.7	15
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
0.7692	Intermediate Similarity	NPC95381
0.6923	Remote Similarity	NPC226250
0.6818	Remote Similarity	NPC261453
0.6818	Remote Similarity	NPC474967
0.6818	Remote Similarity	NPC33749
0.6667	Remote Similarity	NPC147654
0.6522	Remote Similarity	NPC328593
0.6383	Remote Similarity	NPC263386
0.6383	Remote Similarity	NPC141791
0.6327	Remote Similarity	NPC474895
0.625	Remote Similarity	NPC203124
0.625	Remote Similarity	NPC607366
0.6154	Remote Similarity	NPC475695
0.6122	Remote Similarity	NPC65791
0.6038	Remote Similarity	NPC476873
0.6	Remote Similarity	NPC150610
0.5957	Remote Similarity	NPC48315
0.5833	Remote Similarity	NPC474275
0.5833	Remote Similarity	NPC147192
0.5833	Remote Similarity	NPC224208
0.5833	Remote Similarity	NPC41661
0.5814	Remote Similarity	NPC304638
0.5745	Remote Similarity	NPC233669
0.5745	Remote Similarity	NPC275519
0.5745	Remote Similarity	NPC217052
0.5745	Remote Similarity	NPC329344
0.5745	Remote Similarity	NPC237506
0.5745	Remote Similarity	NPC32626
0.5667	Remote Similarity	NPC229784
0.5625	Remote Similarity	NPC281277
0.5556	Remote Similarity	NPC482045
0.5532	Remote Similarity	NPC27352
0.551	Remote Similarity	NPC309434
0.5472	Remote Similarity	NPC232880
0.5472	Remote Similarity	NPC155209
0.5385	Remote Similarity	NPC251407
0.5385	Remote Similarity	NPC168653
0.5357	Remote Similarity	NPC474875
0.5333	Remote Similarity	NPC470572
0.525	Remote Similarity	NPC131587
0.5192	Remote Similarity	NPC132921
0.5192	Remote Similarity	NPC168799
0.5192	Remote Similarity	NPC106406
0.5185	Remote Similarity	NPC258469
0.5185	Remote Similarity	NPC43158
0.5185	Remote Similarity	NPC610147
0.5161	Remote Similarity	NPC477293
0.5122	Remote Similarity	NPC19149
0.5116	Remote Similarity	NPC253746
0.5111	Remote Similarity	NPC94343
0.5102	Remote Similarity	NPC260952
0.5102	Remote Similarity	NPC82731
0.5094	Remote Similarity	NPC470849
0.5094	Remote Similarity	NPC488563
0.5091	Remote Similarity	NPC26241
0.5079	Remote Similarity	NPC287597

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC217472 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4013
0.1-0.2	4984
0.2-0.3	141
0.3-0.4	10
0.4-0.5	2
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