NPASS Compound

Natural Product: NPC245650

Natural Product ID	NPC245650
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2E,4E)-N-Isobutyl-6-Oxohepta-2,4-Dienamide
IUPAC Name	(2E,4E)-N-(2-methylpropyl)-6-oxohepta-2,4-dienamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL556470
PubChem CID	25195169
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000331] Fatty amides [CHEMONTID:0001096] N-acyl amines

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 31 30 0 0 0 0 0 0 0 0999 V2000 -4.5200 1.4586 -0.8505 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1592 0.8028 -0.8451 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6506 0.8412 0.6025 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3620 0.2208 0.6124 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.2450 -1.0389 0.5057 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1212 -1.5811 0.5265 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1841 -0.8232 0.6483 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5453 -1.3362 0.6714 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6082 -0.5636 0.7946 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9673 -1.0713 0.8181 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1987 -2.2924 0.7205 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0974 -0.1347 0.9593 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3600 -1.8201 0.3794 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1934 1.4167 -1.8002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9535 1.4481 0.1698 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2179 0.9453 -1.5629 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4429 2.5349 -1.1484 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2757 -0.2646 -1.0993 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6105 1.8937 0.9666 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4175 0.3474 1.2243 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3049 -2.6544 0.4397 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0063 0.2504 0.7353 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7167 -2.3963 0.5851 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3788 0.5028 0.8784 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6374 -0.0770 -0.0155 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7240 0.8513 1.2411 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7856 -0.5277 1.7365 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2112 -1.6379 0.8678 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1947 1.4702 -1.3011 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0163 0.7840 -2.7124 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4454 2.4512 -2.1052 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 2 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 10 12 1 0 5 13 1 0 2 14 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 6 21 1 0 7 22 1 0 8 23 1 0 9 24 1 0 12 25 1 0 12 26 1 0 12 27 1 0 13 28 1 0 14 29 1 0 14 30 1 0 14 31 1 0 M END

Standard InCHIKey	WOZPVGYGEASHHK-YDFGWWAZSA-N
Standard InCHI	InChI=1S/C11H17NO2/c1-9(2)8-12-11(14)7-5-4-6-10(3)13/h4-7,9H,8H2,1-3H3,(H,12,14)/b6-4+,7-5+
SMILES	CC(CN=C(/C=C/C=C/C(=O)C)O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	195.13	Volume:	216.844 ? Van der Waals volume.
Dense:	0.9	LogP:	1.109 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.226 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.72 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	4.0
TPSA:	49.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.317	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.408	Fsp³:	0.455
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:	0.085	Fluc inhibitor:	0.488 ? 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:	0.025 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.652	Promiscuous compounds:	0.165

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.538	MDCK Permeability:	-4.587
Pgp-inhibitor:	0.582	Pgp-substrate:	0.47
PAMPA:	0.556 ? 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):	0.026
20% Bioavailability (F20%):	0.322	30% Bioavailability (F30%):	0.829
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.472
Plasma Protein Binding (PPB):	68.105%	Volume Distribution (VD):	-0.363
Fu:	30.761% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.987
OATP1B3 inhibitor:	0.961	BCRP inhibitor:	0.01
BSEP inhibitor:	0.954

ADMET: Metabolism

CYP1A2-inhibitor:	0.286	CYP1A2-substrate:	0.922
CYP2C19-inhibitor:	0.888	CYP2C19-substrate:	0.876
CYP2C9-inhibitor:	0.012	CYP2C9-substrate:	0.372
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.062
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	0.865
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.554 ? 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):

9.0

Half-life (T1/2):

0.767

ADMET: Toxicity

hERG Blockers:	0.066	hERG Blockers (10um):	0.18
Human Hepatotoxicity (H-HT):	0.96	Drug-induced Liver Injury (DILI):	0.954
AMES Toxicity:	0.899	Rat Oral Acute Toxicity:	0.437
Maximum Recommended Daily Dose:	0.544	Skin Sensitization:	0.993
Carcinogencity:	0.892	Eye Corrosion:	0.05
Eye Irritation:	0.917	Respiratory Toxicity:	0.822
Drug-induced Neurotoxicity:	0.508	Ototoxicity:	0.443
Hematotoxicity:	0.418	Drug-induced Nephrotoxicity:	0.84
Genotoxicity:	0.856	RPMI-8226 Immunitoxicity:	0.032
A549 Cytotoxicity:	0.023	Hek293 Cytotoxicity:	0.208
BCF:	0.932 ? 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:	3.613 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.904 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.47 ? 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
NPO23557	Zanthoxylum ailanthoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19128011]
NPO23557	Zanthoxylum ailanthoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23557	Zanthoxylum ailanthoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23557	Zanthoxylum ailanthoides	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23557	Zanthoxylum ailanthoides	Species	Rutaceae	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
IC50	2

Activity Type	# Activity
Non-molecular	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
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	4.2	ug.mL-1	PMID[19128011]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	=	6.2	ug.mL-1	PMID[19128011]

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 NPC245650 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	34754
0.1-0.2	14803
0.2-0.3	235
0.3-0.4	31
0.4-0.5	13
0.5-0.6	17
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
0.6471	Remote Similarity	NPC145032
0.6471	Remote Similarity	NPC307435
0.6471	Remote Similarity	NPC304223
0.6471	Remote Similarity	NPC54542
0.6286	Remote Similarity	NPC267340
0.5833	Remote Similarity	NPC243539
0.575	Remote Similarity	NPC6795
0.5676	Remote Similarity	NPC195986
0.5556	Remote Similarity	NPC267692
0.5526	Remote Similarity	NPC104138
0.5526	Remote Similarity	NPC273023
0.5526	Remote Similarity	NPC24216
0.5526	Remote Similarity	NPC306420
0.5385	Remote Similarity	NPC261158
0.5385	Remote Similarity	NPC303672
0.5349	Remote Similarity	NPC187315
0.5238	Remote Similarity	NPC305288
0.5238	Remote Similarity	NPC14326
0.5238	Remote Similarity	NPC163912
0.5122	Remote Similarity	NPC167759
0.5122	Remote Similarity	NPC56028
0.5122	Remote Similarity	NPC123669

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC245650 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6248
0.1-0.2	2838
0.2-0.3	63
0.3-0.4	1
0.4-0.5	0
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