NPASS Compound

Natural Product: NPC544487

Natural Product ID	NPC544487
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Butyl isobutyrate
IUPAC Name	butyl 2-methylpropanoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 26 25 0 0 0 0 0 0 0 0999 V2000 4.0562 -0.7600 -0.5388 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1984 0.3323 0.0554 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7641 -0.1538 0.1689 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9416 0.9650 0.7653 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3823 0.5216 0.8753 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2036 0.1270 -0.1369 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7889 0.1431 -1.3026 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5780 -0.3136 0.1815 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3616 0.7819 0.8562 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2374 -0.8219 -1.0579 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8226 -0.8884 -1.6320 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1007 -0.5250 -0.3417 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7174 -1.7154 -0.0664 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2430 1.2813 -0.5088 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5516 0.4894 1.1023 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3716 -0.4809 -0.7906 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6895 -1.0053 0.8865 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3741 1.1955 1.7681 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0425 1.8608 0.1133 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5542 -1.1722 0.9146 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8105 1.0645 1.7804 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5020 1.6643 0.2126 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3384 0.3395 1.1946 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1458 -1.3823 -0.7728 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5544 -1.5421 -1.5467 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4164 -0.0053 -1.7732 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 1 0 6 7 2 0 6 8 1 0 8 9 1 0 8 10 1 0 1 11 1 0 1 12 1 0 1 13 1 0 2 14 1 0 2 15 1 0 3 16 1 0 3 17 1 0 4 18 1 0 4 19 1 0 8 20 1 0 9 21 1 0 9 22 1 0 9 23 1 0 10 24 1 0 10 25 1 0 10 26 1 0 M END

Standard InCHIKey	JSLCOZYBKYHZNL-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C8H16O2/c1-4-5-6-10-8(9)7(2)3/h7H,4-6H2,1-3H3
SMILES	CCCCOC(=O)C(C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	144.12	Volume:	161.868 ? Van der Waals volume.
Dense:	0.89	LogP:	2.495 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.298 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.867 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	1.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.445	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.838	Fsp³:	0.875
MCE-18:	0.0 ? 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:	0.03	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	1.0	Promiscuous compounds:	0.089

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.443	MDCK Permeability:	-4.595
Pgp-inhibitor:	0.302	Pgp-substrate:	0.225
PAMPA:	0.149 ? 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):	0.068
20% Bioavailability (F20%):	0.651	30% Bioavailability (F30%):	0.558
50% Bioavailability (F50%):	0.734

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.413	MRP1:	0.97
Plasma Protein Binding (PPB):	68.342%	Volume Distribution (VD):	0.163
Fu:	29.449% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.233
OATP1B3 inhibitor:	0.886	BCRP inhibitor:	0.318
BSEP inhibitor:	0.985

ADMET: Metabolism

CYP1A2-inhibitor:	0.138	CYP1A2-substrate:	0.988
CYP2C19-inhibitor:	0.778	CYP2C19-substrate:	0.014
CYP2C9-inhibitor:	0.013	CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.116
CYP3A4-inhibitor:	0.993	CYP3A4-substrate:	0.941
CYP2B6-substrate:	0.015	CYP2C8-inhibitor:	0.993
HLM stability:	0.719 ? 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):

8.257

Half-life (T1/2):

0.43

ADMET: Toxicity

hERG Blockers:	0.168	hERG Blockers (10um):	0.628
Human Hepatotoxicity (H-HT):	0.243	Drug-induced Liver Injury (DILI):	0.293
AMES Toxicity:	0.167	Rat Oral Acute Toxicity:	0.19
Maximum Recommended Daily Dose:	0.106	Skin Sensitization:	0.565
Carcinogencity:	0.522	Eye Corrosion:	0.959
Eye Irritation:	0.992	Respiratory Toxicity:	0.399
Drug-induced Neurotoxicity:	0.21	Ototoxicity:	0.201
Hematotoxicity:	0.129	Drug-induced Nephrotoxicity:	0.257
Genotoxicity:	0.006	RPMI-8226 Immunitoxicity:	0.043
A549 Cytotoxicity:	0.03	Hek293 Cytotoxicity:	0.087
BCF:	1.059 ? 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:	2.905 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.086 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.867 ? 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
NPO54898	Artemisia magellanica	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31241852]
NPO22103	Ammi visnaga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38256954]
NPO52418	Heracleum persicum	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39519893]
NPO22103	Ammi visnaga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO22103	Ammi visnaga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO22103	Ammi visnaga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO22103	Ammi visnaga	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO22103	Ammi visnaga	Species	Apiaceae	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
NPO52418	Heracleum persicum	Oil	n.a.	0.5 Â± 0.0	n.a.	n.a.	%	PMID[39519893]
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

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

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 NPC544487 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	25951
0.1-0.2	22767
0.2-0.3	1032
0.3-0.4	61
0.4-0.5	27
0.5-0.6	6
0.6-0.7	5
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
0.7826	Intermediate Similarity	NPC155872
0.7391	Intermediate Similarity	NPC35371
0.6667	Remote Similarity	NPC3693
0.6667	Remote Similarity	NPC476549
0.6364	Remote Similarity	NPC140229
0.6154	Remote Similarity	NPC187922
0.6087	Remote Similarity	NPC166804
0.5926	Remote Similarity	NPC14608
0.5417	Remote Similarity	NPC248233
0.5385	Remote Similarity	NPC476550
0.5385	Remote Similarity	NPC601675
0.5217	Remote Similarity	NPC127696
0.52	Remote Similarity	NPC40965

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC544487 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6449
0.1-0.2	2551
0.2-0.3	133
0.3-0.4	13
0.4-0.5	3
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
0.5833	Remote Similarity	NPD900	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