NPASS Compound

Natural Product: NPC2596

Natural Product ID	NPC2596
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(4-Hydroxyphenyl)Ethyl 4-Methoxybenzoate
IUPAC Name	2-(4-hydroxyphenyl)ethyl 4-methoxybenzoate
Synonyms	P-Hydroxyphenethyl Anisate
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1078244
PubChem CID	14704104
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0002344] Methoxybenzoic acids and derivatives [CHEMONTID:0002346] P-methoxybenzoic 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 36 37 0 0 0 0 0 0 0 0999 V2000 7.2968 0.1121 -0.7736 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4599 -0.1041 0.3369 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0846 -0.1416 0.1743 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2345 -0.3509 1.2374 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8753 -0.3826 1.0433 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2925 -0.2116 -0.1944 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1505 -0.0022 -1.2566 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5064 0.0300 -1.0661 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8500 -0.2480 -0.3835 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3044 -0.0945 -1.5011 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0107 -0.4594 0.6965 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3689 -0.5005 0.5555 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9966 0.7348 0.0147 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4770 0.4920 -0.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0366 -0.0414 -1.2042 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4117 -0.2762 -1.2980 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2260 0.0249 -0.2433 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6640 0.5568 0.8950 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3251 0.7838 0.9825 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6075 -0.2041 -0.3203 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9788 0.9553 -1.4103 H 0 0 0 0 0 0 0 0 0 0 0 0 8.3197 0.3660 -0.4124 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3159 -0.8136 -1.3887 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6913 -0.4852 2.2097 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2270 -0.5515 1.9125 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7670 0.1381 -2.2449 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1529 0.1962 -1.9193 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8153 -0.7113 1.5473 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6024 -1.3349 -0.1694 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8771 1.5506 0.7697 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6804 1.0273 -0.9861 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3936 -0.2824 -2.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8274 -0.6938 -2.2011 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3096 0.7938 1.7268 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9362 1.2024 1.8975 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9627 -1.0743 0.0589 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 6 9 1 0 9 10 2 0 9 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 17 20 1 0 8 3 1 0 19 14 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 5 25 1 0 7 26 1 0 8 27 1 0 12 28 1 0 12 29 1 0 13 30 1 0 13 31 1 0 15 32 1 0 16 33 1 0 18 34 1 0 19 35 1 0 20 36 1 0 M END

Standard InCHIKey	DSMAYKYXHOGICG-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H16O4/c1-19-15-8-4-13(5-9-15)16(18)20-11-10-12-2-6-14(17)7-3-12/h2-9,17H,10-11H2,1H3
SMILES	COc1ccc(cc1)C(=O)OCCc1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	272.1	Volume:	284.885 ? Van der Waals volume.
Dense:	0.955	LogP:	3.587 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.387 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.802 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	13.0
TPSA:	55.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.85	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.602	Fsp³:	0.188
MCE-18:	11.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.325	Fluc inhibitor:	0.957 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.015 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.581 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.917	Promiscuous compounds:	0.531

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.647	MDCK Permeability:	-4.461
Pgp-inhibitor:	0.248	Pgp-substrate:	0.15
PAMPA:	0.126 ? 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):	0.073
20% Bioavailability (F20%):	0.763	30% Bioavailability (F30%):	0.729
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.036	MRP1:	0.291
Plasma Protein Binding (PPB):	91.858%	Volume Distribution (VD):	-0.03
Fu:	9.577% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.984
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.639
BSEP inhibitor:	0.908

ADMET: Metabolism

CYP1A2-inhibitor:	0.123	CYP1A2-substrate:	0.991
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.96
CYP2C9-inhibitor:	0.127	CYP2C9-substrate:	0.526
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.051
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	1.0 ? 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):

8.153

Half-life (T1/2):

0.366

ADMET: Toxicity

hERG Blockers:	0.367	hERG Blockers (10um):	0.78
Human Hepatotoxicity (H-HT):	0.098	Drug-induced Liver Injury (DILI):	0.312
AMES Toxicity:	0.188	Rat Oral Acute Toxicity:	0.051
Maximum Recommended Daily Dose:	0.239	Skin Sensitization:	0.364
Carcinogencity:	0.729	Eye Corrosion:	0.041
Eye Irritation:	0.977	Respiratory Toxicity:	0.154
Drug-induced Neurotoxicity:	0.454	Ototoxicity:	0.136
Hematotoxicity:	0.02	Drug-induced Nephrotoxicity:	0.061
Genotoxicity:	0.042	RPMI-8226 Immunitoxicity:	0.044
A549 Cytotoxicity:	0.061	Hek293 Cytotoxicity:	0.621
BCF:	1.502 ? 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:	4.309 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.168 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.796 ? 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
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	Roots	Zhang County, Gansu Province, China	2002-Sep	PMID[19702283]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	rhizome	n.a.	PMID[20707067]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	root	n.a.	PMID[20707067]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	n.a.	root	n.a.	PMID[21534583]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	Roots	n.a.	n.a.	PMID[23691978]
NPO2392	Hansenia weberbaueriana	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25333853]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[37382684]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2392	Hansenia weberbaueriana	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24644	Hansenia forbesii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30125	Notopterygium forbesii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2953	Ostericum grosseserratum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30125	Notopterygium forbesii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO24644	Hansenia forbesii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2392	Hansenia weberbaueriana	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO30526	Notopterygium incisum	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO30125	Notopterygium forbesii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO24644	Hansenia forbesii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2392	Hansenia weberbaueriana	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2953	Ostericum grosseserratum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO2953	Ostericum grosseserratum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24644	Hansenia forbesii	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25837	Euphorbia micractina	Species	Euphorbiaceae	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
Potency	24

Activity Type	# Activity
Individual protein	15
Cell line	1
Organism	2
Nucleic acid	2
Others	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	14125.4	nM	PubChem BioAssay data set
NPT157	Individual protein	Breast cancer type 1 susceptibility protein	Homo sapiens	Potency	n.a.	5011.9	nM	PubChem BioAssay data set
NPT160	Individual protein	TAR DNA-binding protein 43	Homo sapiens	Potency	n.a.	19952.6	nM	PubChem BioAssay data set
NPT537	Individual protein	Ras-related protein Rab-9A	Homo sapiens	Potency	=	4466.8	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	12589.3	nM	PubChem BioAssay data set
NPT531	Individual protein	Nuclear receptor ROR-gamma	Mus musculus	Potency	=	7079.5	nM	PubChem BioAssay data set
NPT54	Individual protein	Nonstructural protein 1	Influenza A virus	Potency	=	10000.0	nM	PubChem BioAssay data set
NPT538	Individual protein	Niemann-Pick C1 protein	Homo sapiens	Potency	=	3981.1	nM	PubChem BioAssay data set
NPT484	Individual protein	Luciferin 4-monooxygenase	Photinus pyralis	Potency	n.a.	6745.6	nM	PubChem BioAssay data set
NPT93	Individual protein	Survival motor neuron protein	Homo sapiens	Potency	=	354.8	nM	PubChem BioAssay data set
NPT51	Individual protein	Microtubule-associated protein tau	Homo sapiens	Potency	=	8912.5	nM	PubChem BioAssay data set
NPT536	Nucleic acid	microRNA 21	Homo sapiens	Potency	=	6561.4	nM	PubChem BioAssay data set
NPT56	Individual protein	Beta-lactamase AmpC	Escherichia coli K-12	Potency	=	794.3	nM	PubChem BioAssay data set
NPT539	Individual protein	Cellular tumor antigen p53	Homo sapiens	Potency	n.a.	56234.1	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	12995.3	nM	PubChem BioAssay data set
NPT64	Individual protein	ATPase family AAA domain-containing protein 5	Homo sapiens	Potency	n.a.	10322.5	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT71	Cell line	HEK293	Homo sapiens	Potency	n.a.	8199.5	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	13115.4	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	10417.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	23109.3	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	6309.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	6513.1	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	2511.9	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 NPC2596 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	22228
0.1-0.2	20953
0.2-0.3	6064
0.3-0.4	580
0.4-0.5	30
0.5-0.6	3
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	Natural Product ID
0.5476	Remote Similarity	NPC602256
0.5227	Remote Similarity	NPC42211
0.5116	Remote Similarity	NPC27633

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC2596 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3369
0.1-0.2	5317
0.2-0.3	432
0.3-0.4	30
0.4-0.5	1
0.5-0.6	1
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
0.5116	Remote Similarity	NPD9545	Pre-clinical

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