NPASS Compound

Natural Product: NPC220893

Natural Product ID	NPC220893
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Benzyl 3-Methylbutanoate
IUPAC Name	benzyl 3-methylbutanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3184059
PubChem CID	7651
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0001097] Benzyloxycarbonyls

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 30 30 0 0 0 0 0 0 0 0999 V2000 2.1906 -1.0309 0.6934 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8384 -0.1960 -0.3644 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2571 0.1965 -0.0292 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0585 1.0954 -0.5318 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6523 0.8078 -0.9328 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0790 1.8017 -1.0981 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1640 -0.4409 -1.1154 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.1156 -0.8117 -1.4837 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1438 -0.3559 -0.5206 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8607 0.8043 -0.7060 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8165 1.2251 0.2269 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0376 0.4566 1.3487 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3102 -0.7108 1.5252 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3695 -1.1357 0.6190 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3151 -0.5090 1.1536 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8917 -1.2593 1.5297 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7575 -1.9776 0.2632 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8441 -0.7746 -1.3334 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7492 0.4417 -1.0107 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8196 -0.6023 0.4689 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2855 1.1589 0.5432 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0452 1.5833 0.4700 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5988 1.6968 -1.2919 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3969 -0.4978 -2.5190 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1932 -1.9380 -1.5276 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6737 1.3772 -1.6005 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3443 2.1472 0.0202 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7706 0.7706 2.0732 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5301 -1.2744 2.4304 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8257 -2.0484 0.7927 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 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 14 9 1 0 1 15 1 0 1 16 1 0 1 17 1 0 2 18 1 0 3 19 1 0 3 20 1 0 3 21 1 0 4 22 1 0 4 23 1 0 8 24 1 0 8 25 1 0 10 26 1 0 11 27 1 0 12 28 1 0 13 29 1 0 14 30 1 0 M END

Standard InCHIKey	HVJKZICIMIWFCP-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H16O2/c1-10(2)8-12(13)14-9-11-6-4-3-5-7-11/h3-7,10H,8-9H2,1-2H3
SMILES	CC(C)CC(=O)OCc1ccccc1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	192.12	Volume:	214.586 ? Van der Waals volume.
Dense:	0.895	LogP:	3.32 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.998 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.36 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	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:	0.686	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.525	Fsp³:	0.417
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:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.095	Fluc inhibitor:	0.078 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.014 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.253 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.987	Promiscuous compounds:	0.014

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.58	MDCK Permeability:	-4.304
Pgp-inhibitor:	0.175	Pgp-substrate:	0.0
PAMPA:	0.235 ? 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):	0.023
20% Bioavailability (F20%):	0.021	30% Bioavailability (F30%):	0.619
50% Bioavailability (F50%):	0.297

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.941	MRP1:	0.414
Plasma Protein Binding (PPB):	87.17%	Volume Distribution (VD):	-0.299
Fu:	13.195% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.97
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.003
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.186	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.902	CYP2C19-substrate:	0.946
CYP2C9-inhibitor:	0.066	CYP2C9-substrate:	0.028
CYP2D6-inhibitor:	0.002	CYP2D6-substrate:	0.618
CYP3A4-inhibitor:	0.984	CYP3A4-substrate:	0.991
CYP2B6-substrate:	0.602	CYP2C8-inhibitor:	0.999
HLM stability:	0.685 ? 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):

8.06

Half-life (T1/2):

0.864

ADMET: Toxicity

hERG Blockers:	0.157	hERG Blockers (10um):	0.634
Human Hepatotoxicity (H-HT):	0.261	Drug-induced Liver Injury (DILI):	0.21
AMES Toxicity:	0.329	Rat Oral Acute Toxicity:	0.118
Maximum Recommended Daily Dose:	0.194	Skin Sensitization:	0.701
Carcinogencity:	0.643	Eye Corrosion:	0.787
Eye Irritation:	0.982	Respiratory Toxicity:	0.243
Drug-induced Neurotoxicity:	0.497	Ototoxicity:	0.143
Hematotoxicity:	0.177	Drug-induced Nephrotoxicity:	0.332
Genotoxicity:	0.04	RPMI-8226 Immunitoxicity:	0.056
A549 Cytotoxicity:	0.036	Hek293 Cytotoxicity:	0.099
BCF:	1.297 ? 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:	3.972 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.197 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.809 ? 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
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[ 21030913]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	leaf	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	flower	n.a.	DOI[10.1007/s11418-006-0112-9]
NPO54898	Artemisia magellanica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31241852]
NPO44665	Achillea coarctata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36006860]
NPO23312	Matricaria aurea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37896017]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[6387056]
NPO44665	Achillea coarctata	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23312	Matricaria aurea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26589	Artemisia annua L.	Strain	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23312	Matricaria aurea	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26589	Artemisia annua L.	Strain	Asteraceae	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
NPO23312	Matricaria aurea	Oil	Aerial parts	0.1	n.a.	n.a.	%	PMID[37896017]
NPO44665	Achillea coarctata	Oil	n.a.	0.2	n.a.	n.a.	%	PMID[36006860]
NPO44665	Achillea coarctata	Oil	n.a.	0.1	n.a.	n.a.	%	PMID[36006860]
NPO44665	Achillea coarctata	Oil	n.a.	0.3	n.a.	n.a.	%	PMID[36006860]
NPO44665	Achillea coarctata	Oil	n.a.	0.4	n.a.	n.a.	%	PMID[36006860]
NPO44665	Achillea coarctata	Oil	n.a.	0.5	n.a.	n.a.	%	PMID[36006860]
NPO54898	Artemisia magellanica	Oil	n.a.	0.1	n.a.	n.a.	%	PMID[31241852]

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	4

Activity Type	# Activity
Others	4

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.	68589.6	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	24336.5	nM	PubChem BioAssay data set
NPT2	Others	Unspecified	n.a.	Potency	n.a.	12301.3	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	LD50	>	5000.0	mg/kg	ToxVal
-	Oryctolagus cuniculus	LD50	>	5000.0	mg/kg	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 NPC220893 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	12465
0.1-0.2	34539
0.2-0.3	2720
0.3-0.4	120
0.4-0.5	6
0.5-0.6	4
0.6-0.7	1
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
0.6552	Remote Similarity	NPC58616
0.5882	Remote Similarity	NPC173443
0.5517	Remote Similarity	NPC165212
0.5517	Remote Similarity	NPC5324
0.5161	Remote Similarity	NPC52330

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC220893 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	2468
0.1-0.2	5873
0.2-0.3	767
0.3-0.4	40
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