NPASS Compound

Natural Product: NPC181709

Natural Product ID	NPC181709
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Methyl P-Hydroxycinnamyl Ketone
IUPAC Name	(E)-4-(4-hydroxyphenyl)but-3-en-2-one
Synonyms	Methyl P-Hydroxycinnamyl Ketone
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL9184
PubChem CID	796857
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000476] Cinnamic acids and derivatives [CHEMONTID:0001391] Hydroxycinnamic 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

Standard InCHIKey	OCNIKEFATSKIBE-NSCUHMNNSA-N
Standard InCHI	InChI=1S/C10H10O2/c1-8(11)2-3-9-4-6-10(12)7-5-9/h2-7,12H,1H3/b3-2+
SMILES	CC(=O)/C=C/c1ccc(cc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	162.07	Volume:	177.358 ? Van der Waals volume.
Dense:	0.914	LogP:	2.018 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.075 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.432 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	8.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.675	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.914	Fsp³:	0.1
MCE-18:	6.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.419	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.019 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.185 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.999	Promiscuous compounds:	0.435

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.706	MDCK Permeability:	-4.78
Pgp-inhibitor:	0.362	Pgp-substrate:	0.075
PAMPA:	0.332 ? 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):	0.013
20% Bioavailability (F20%):	0.84	30% Bioavailability (F30%):	0.78
50% Bioavailability (F50%):	0.984

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.016	MRP1:	0.297
Plasma Protein Binding (PPB):	79.588%	Volume Distribution (VD):	-0.215
Fu:	19.104% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.978
OATP1B3 inhibitor:	0.983	BCRP inhibitor:	0.221
BSEP inhibitor:	0.931

ADMET: Metabolism

CYP1A2-inhibitor:	0.141	CYP1A2-substrate:	0.71
CYP2C19-inhibitor:	0.017	CYP2C19-substrate:	0.187
CYP2C9-inhibitor:	0.104	CYP2C9-substrate:	0.463
CYP2D6-inhibitor:	0.958	CYP2D6-substrate:	0.081
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.987
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.116 ? 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):

11.502

Half-life (T1/2):

1.01

ADMET: Toxicity

hERG Blockers:	0.221	hERG Blockers (10um):	0.497
Human Hepatotoxicity (H-HT):	0.791	Drug-induced Liver Injury (DILI):	0.218
AMES Toxicity:	0.492	Rat Oral Acute Toxicity:	0.077
Maximum Recommended Daily Dose:	0.31	Skin Sensitization:	0.944
Carcinogencity:	0.264	Eye Corrosion:	0.87
Eye Irritation:	0.997	Respiratory Toxicity:	0.497
Drug-induced Neurotoxicity:	0.802	Ototoxicity:	0.157
Hematotoxicity:	0.106	Drug-induced Nephrotoxicity:	0.193
Genotoxicity:	0.444	RPMI-8226 Immunitoxicity:	0.049
A549 Cytotoxicity:	0.112	Hek293 Cytotoxicity:	0.207
BCF:	1.055 ? 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:	3.622 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.696 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.438 ? 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
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[ 10835233]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Fruit	n.a.	n.a.	DOI[10.1016/S0963-9969(99)00095-2]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	seeds	Mengha, Yunnan Province, China	1991-Aug	PMID[11277741]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	seeds	n.a.	n.a.	PMID[11325233]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	Seeds	n.a.	n.a.	PMID[11430002]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[21381697]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[37570937]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9461664]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Leaf	n.a.	n.a.	Database[FooDB]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Fruits	n.a.		Database[FooDB]
NPO19774	Rubus idaeus	Species	n.a.	n.a.		n.a.	n.a.	Database[FooDB]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Seed	n.a.	n.a.	Database[FooDB]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Fruit	n.a.	n.a.	Database[FooDB]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	Fruits	n.a.		Database[Phenol-Explorer]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.		Database[Phenol-Explorer]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO6836	Alpinia blepharocalyx	Species	Zingiberaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19774	Rubus idaeus	Species	n.a.	n.a.	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	6
ED50	2
Ratio IC50	1
Activity	3

Activity Type	# Activity
Cell line	6
Organism	3
Non-molecular	1
Others	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
NPT111	Cell line	K562	Homo sapiens	IC50	=	60000.0	nM	DOI[10.1016/S0960-894X(97)10147-0]
NPT453	Cell line	HT-1080	Homo sapiens	ED50	>	100.0	uM	PMID[11277741]
NPT804	Cell line	HT-22	Mus musculus	Activity	=	50.0	%	PMID[25313922]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	ED50	>	100.0	uM	PMID[11277741]
NPT21334	Cell line	MC3T3-E1	Mus musculus	Activity	=	110.0	%	PMID[31257875]
NPT21334	Cell line	MC3T3-E1	Mus musculus	Activity	=	150.0	%	PMID[31257875]
NPT19	Organism	Escherichia coli	Escherichia coli	IC50	=	1202264.43	nM	PMID[12161116]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	IC50	=	1803017740859.57	nM	PMID[15911266]
NPT419	Organism	Oryctolagus cuniculus	Oryctolagus cuniculus	IC50	=	66069.34	nM	PMID[15911266]
NPT2	Others	Unspecified	n.a.	Ratio IC50	>	5.0	n.a.	PMID[21500839]
NPT2	Others	Unspecified	n.a.	IC50	>	50000.0	nM	PMID[21500839]

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 NPC181709 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	13677
0.1-0.2	29975
0.2-0.3	5384
0.3-0.4	680
0.4-0.5	113
0.5-0.6	18
0.6-0.7	6
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
0.7419	Intermediate Similarity	NPC68269
0.7097	Intermediate Similarity	NPC79672
0.6786	Remote Similarity	NPC248817
0.6452	Remote Similarity	NPC286006
0.6389	Remote Similarity	NPC201967
0.6389	Remote Similarity	NPC51698
0.6053	Remote Similarity	NPC130193
0.6	Remote Similarity	NPC311343
0.5833	Remote Similarity	NPC171843
0.5806	Remote Similarity	NPC239808
0.5714	Remote Similarity	NPC253746
0.5714	Remote Similarity	NPC17525
0.5676	Remote Similarity	NPC304638
0.5625	Remote Similarity	NPC104216
0.561	Remote Similarity	NPC14007
0.5588	Remote Similarity	NPC184169
0.5476	Remote Similarity	NPC71941
0.5476	Remote Similarity	NPC88141
0.5294	Remote Similarity	NPC175298
0.525	Remote Similarity	NPC116842
0.5238	Remote Similarity	NPC472585
0.5227	Remote Similarity	NPC285350
0.5172	Remote Similarity	NPC265146
0.5128	Remote Similarity	NPC19174
0.5128	Remote Similarity	NPC73532
0.5128	Remote Similarity	NPC115159

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC181709 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3489
0.1-0.2	5336
0.2-0.3	294
0.3-0.4	25
0.4-0.5	6
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