NPASS Compound

Natural Product: NPC298224

Natural Product ID	NPC298224
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	4-(4-Methoxyphenyl)Butan-2-One
IUPAC Name	4-(4-methoxyphenyl)butan-2-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3184371
PubChem CID	61007
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002341] Phenol ethers [CHEMONTID:0000138] Anisoles

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 27 27 0 0 0 0 0 0 0 0999 V2000 4.7966 0.3050 0.1379 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6388 -0.5032 0.5966 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8506 -1.5960 1.0840 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2436 -0.0295 0.4784 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3371 -1.1136 -0.0503 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0383 -0.5832 -0.1346 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5567 0.0354 -1.2586 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8441 0.5156 -1.2873 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6746 0.3995 -0.1951 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1945 -0.2096 0.9397 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8999 -0.6821 0.9423 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9511 0.9135 -0.3302 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9437 0.8902 0.6689 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8960 1.2431 0.7100 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7478 -0.2741 0.1684 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6171 0.6036 -0.9413 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1884 0.8343 -0.2013 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8515 0.2350 1.4995 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6728 -1.2913 -1.1147 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3471 -2.0246 0.5295 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0707 0.1322 -2.1081 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2174 1.0011 -2.2000 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8490 -0.2985 1.8009 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5285 -1.1768 1.8522 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5114 -0.0515 0.5648 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4415 0.9573 1.6512 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6074 1.7681 0.5045 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 9 12 1 0 12 13 1 0 11 6 1 0 1 14 1 0 1 15 1 0 1 16 1 0 4 17 1 0 4 18 1 0 5 19 1 0 5 20 1 0 7 21 1 0 8 22 1 0 10 23 1 0 11 24 1 0 13 25 1 0 13 26 1 0 13 27 1 0 M END

Standard InCHIKey	PCBSXBYCASFXTM-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C11H14O2/c1-9(12)3-4-10-5-7-11(13-2)8-6-10/h5-8H,3-4H2,1-2H3
SMILES	CC(=O)CCc1ccc(cc1)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	178.1	Volume:	197.29 ? Van der Waals volume.
Dense:	0.903	LogP:	1.981 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.027 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.879 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	7.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	1.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.706	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.461	Fsp³:	0.364
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:	0.04	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.028 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.06 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.997	Promiscuous compounds:	0.015

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.714	MDCK Permeability:	-4.512
Pgp-inhibitor:	0.959	Pgp-substrate:	0.203
PAMPA:	0.044 ? 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):	0.077
20% Bioavailability (F20%):	0.128	30% Bioavailability (F30%):	0.17
50% Bioavailability (F50%):	0.775

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.104	MRP1:	0.25
Plasma Protein Binding (PPB):	97.379%	Volume Distribution (VD):	-0.188
Fu:	2.159% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.709
OATP1B3 inhibitor:	0.774	BCRP inhibitor:	0.669
BSEP inhibitor:	0.989

ADMET: Metabolism

CYP1A2-inhibitor:	0.993	CYP1A2-substrate:	0.16
CYP2C19-inhibitor:	0.994	CYP2C19-substrate:	0.669
CYP2C9-inhibitor:	0.993	CYP2C9-substrate:	0.016
CYP2D6-inhibitor:	0.993	CYP2D6-substrate:	0.392
CYP3A4-inhibitor:	0.406	CYP3A4-substrate:	0.014
CYP2B6-substrate:	0.255	CYP2C8-inhibitor:	0.911
HLM stability:	0.802 ? 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):

9.932

Half-life (T1/2):

0.922

ADMET: Toxicity

hERG Blockers:	0.127	hERG Blockers (10um):	0.486
Human Hepatotoxicity (H-HT):	0.527	Drug-induced Liver Injury (DILI):	0.177
AMES Toxicity:	0.325	Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.209	Skin Sensitization:	0.873
Carcinogencity:	0.583	Eye Corrosion:	0.942
Eye Irritation:	0.992	Respiratory Toxicity:	0.572
Drug-induced Neurotoxicity:	0.719	Ototoxicity:	0.416
Hematotoxicity:	0.522	Drug-induced Nephrotoxicity:	0.684
Genotoxicity:	0.011	RPMI-8226 Immunitoxicity:	0.044
A549 Cytotoxicity:	0.011	Hek293 Cytotoxicity:	0.068
BCF:	0.439 ? 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:	2.862 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.907 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.21 ? 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
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1016/S0031-9422(00)94055-X]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	flower	n.a.	DOI[10.3390/70200245]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24617303]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27128895]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[29140705]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	Resinous Wood	n.a.	n.a.	PMID[29227647]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38790803]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38792158]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1983	Fructus anisi stellati	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28295	Foeniculum vulgare	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14558	Aquilaria sinensis	Species	Thymelaeaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13274	Illicium verum	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12588	Cornus officinalis	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12265	Aquilaria agallochum	Species	Thymelaeaceae	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	9
AC50	3

Activity Type	# Activity
Others	12

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
NPT2	Others	Unspecified	n.a.	Potency	n.a.	266	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	27306	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	13685.4	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	61130.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	54941	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	33488.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	118.8	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	21131.7	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	68589.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	AC50	n.a.	8912.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	AC50	n.a.	1258.9	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	AC50	n.a.	1122.0	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
-	Rattus norvegicus	NOAEL	=	500.0	mg/kg-day	ToxVal
-	Rattus norvegicus	LD50	>=	5000.0	mg/kg	ToxVal
-	Rattus norvegicus	LD50	>	5000.0	mg/kg	ToxVal
-	Rattus norvegicus	NOAEL	=	128.0	mg/kg-day	ToxVal
-	Oryctolagus cuniculus	LD50	>	5000.0	mg/kg	ToxVal
-	Homo sapiens	DNEL systemic	=	12.34	mg/m3	ToxVal

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 NPC298224 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	19840
0.1-0.2	25771
0.2-0.3	3834
0.3-0.4	350
0.4-0.5	51
0.5-0.6	8
0.6-0.7	2
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
0.75	Intermediate Similarity	NPC321956
0.6333	Remote Similarity	NPC38209
0.6	Remote Similarity	NPC74458
0.5556	Remote Similarity	NPC474272
0.5484	Remote Similarity	NPC71853
0.5455	Remote Similarity	NPC97811
0.5455	Remote Similarity	NPC605225
0.5385	Remote Similarity	NPC299406
0.5294	Remote Similarity	NPC260000
0.5152	Remote Similarity	NPC42383
0.5122	Remote Similarity	NPC266425

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC298224 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2968
0.1-0.2	5456
0.2-0.3	685
0.3-0.4	36
0.4-0.5	4
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
0.5366	Remote Similarity	NPD1651	Phase 4

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