NPASS Compound

Natural Product: NPC563535

Natural Product ID	NPC563535
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	butyl 2-methylbut-2-enoate
IUPAC Name	butyl 2-methylbut-2-enoate
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 27 26 0 0 0 0 0 0 0 0999 V2000 3.3006 -1.3197 -0.7456 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0135 -0.9269 0.6529 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9585 -0.2007 0.9602 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7051 0.1735 2.3798 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0035 0.2690 -0.0261 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1908 -0.0308 -1.2318 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1000 1.0213 0.2457 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0252 1.4752 -0.7176 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6949 0.3628 -1.4734 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4676 -0.5766 -0.6107 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5781 0.0932 0.1605 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2312 -1.9177 -0.7854 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4955 -1.9616 -1.1866 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4904 -0.3991 -1.3265 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6982 -1.2529 1.4327 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6758 0.5382 2.5330 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8505 -0.7401 3.0205 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3961 0.9796 2.7238 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4329 2.0995 -1.4208 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7884 2.1498 -0.2811 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0120 -0.2169 -2.1012 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4263 0.8453 -2.1712 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9485 -1.3251 -1.2760 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8564 -1.1435 0.1073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5542 -0.4446 0.0568 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7621 1.1311 -0.1723 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3631 0.1069 1.2530 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 3 3 4 1 0 3 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 0 4 16 1 0 4 17 1 0 4 18 1 0 8 19 1 0 8 20 1 0 9 21 1 0 9 22 1 0 10 23 1 0 10 24 1 0 11 25 1 0 11 26 1 0 11 27 1 0 M END

Standard InCHIKey	RBGFLIOXJWFKKX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H16O2/c1-4-6-7-11-9(10)8(3)5-2/h5H,4,6-7H2,1-3H3
SMILES	CC=C(C)C(=O)OCCCC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	156.12	Volume:	176.528 ? Van der Waals volume.
Dense:	0.884	LogP:	2.794 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.511 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.325 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	2.0
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:	0.354	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.249	Fsp³:	0.667
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:	0.01	Fluc inhibitor:	0.246 ? 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:	0.005 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	1.0	Promiscuous compounds:	0.131

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.595	MDCK Permeability:	-4.574
Pgp-inhibitor:	0.055	Pgp-substrate:	0.088
PAMPA:	0.299 ? 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%):	0.649	30% Bioavailability (F30%):	0.808
50% Bioavailability (F50%):	0.717

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.591	MRP1:	0.97
Plasma Protein Binding (PPB):	94.881%	Volume Distribution (VD):	0.334
Fu:	6.353% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.346
OATP1B3 inhibitor:	0.951	BCRP inhibitor:	0.199
BSEP inhibitor:	0.802

ADMET: Metabolism

CYP1A2-inhibitor:	0.219	CYP1A2-substrate:	0.996
CYP2C19-inhibitor:	0.844	CYP2C19-substrate:	0.743
CYP2C9-inhibitor:	0.328	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.003	CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	0.754	CYP3A4-substrate:	0.996
CYP2B6-substrate:	0.227	CYP2C8-inhibitor:	0.738
HLM stability:	0.913 ? 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):

9.096

Half-life (T1/2):

0.678

ADMET: Toxicity

hERG Blockers:	0.145	hERG Blockers (10um):	0.597
Human Hepatotoxicity (H-HT):	0.244	Drug-induced Liver Injury (DILI):	0.315
AMES Toxicity:	0.208	Rat Oral Acute Toxicity:	0.245
Maximum Recommended Daily Dose:	0.191	Skin Sensitization:	0.834
Carcinogencity:	0.648	Eye Corrosion:	0.955
Eye Irritation:	0.993	Respiratory Toxicity:	0.475
Drug-induced Neurotoxicity:	0.237	Ototoxicity:	0.129
Hematotoxicity:	0.101	Drug-induced Nephrotoxicity:	0.218
Genotoxicity:	0.013	RPMI-8226 Immunitoxicity:	0.055
A549 Cytotoxicity:	0.046	Hek293 Cytotoxicity:	0.12
BCF:	1.567 ? 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:	3.476 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.576 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.321 ? 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
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23501116]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24471493]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	Flowers	n.a.	n.a.	PMID[28116906]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	Flower	n.a.	n.a.	Database[FooDB]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO15440	Chamaemelum nobile	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO15440	Chamaemelum nobile	Species	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

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

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 NPC563535 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	23763
0.1-0.2	23578
0.2-0.3	2358
0.3-0.4	114
0.4-0.5	33
0.5-0.6	9
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
0.6786	Remote Similarity	NPC15789
0.6	Remote Similarity	NPC166804
0.5833	Remote Similarity	NPC3693
0.5833	Remote Similarity	NPC476549
0.56	Remote Similarity	NPC140229
0.5385	Remote Similarity	NPC248233
0.5357	Remote Similarity	NPC12904
0.5357	Remote Similarity	NPC476550
0.5333	Remote Similarity	NPC223675
0.5333	Remote Similarity	NPC68577
0.5172	Remote Similarity	NPC286695

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC563535 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6841
0.1-0.2	2195
0.2-0.3	104
0.3-0.4	8
0.4-0.5	0
0.5-0.6	2
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
0.5862	Remote Similarity	NPD9378	Phase 4
0.5769	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