NPASS Compound

Natural Product: NPC235242

Natural Product ID	NPC235242
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(10E,14Z)-9-Oxooctadeca-10,14-Dien-12-Ynoic Acid
IUPAC Name	(10E,14Z)-9-oxooctadeca-10,14-dien-12-ynoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1956877
PubChem CID	57345550
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000262] Fatty acids and conjugates [CHEMONTID:0002949] Long-chain fatty acids

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 47 46 0 0 0 0 0 0 0 0999 V2000 -8.7223 0.9378 0.0002 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2901 1.2307 -0.3774 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4014 0.3728 0.5278 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7604 -1.0352 0.2700 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8372 -1.8594 -0.1741 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5128 -1.3533 -0.3908 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3957 -0.9069 -0.5638 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0849 -0.3579 -0.7687 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9755 -0.9639 -0.3368 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3454 -0.3984 -0.5500 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4762 0.6871 -1.1533 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5224 -1.1266 -0.0426 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9562 -0.6153 1.3068 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3087 0.8433 1.1879 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4416 1.0333 0.2047 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6851 0.2715 0.6575 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7439 0.5539 -0.4174 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0394 -0.1539 -0.0781 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0033 0.1712 -1.1619 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7188 0.9002 -2.1387 O 0 0 0 0 0 0 0 0 0 0 0 0 9.2971 -0.3566 -1.1008 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.7855 0.5136 1.0443 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3232 1.8651 0.0121 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1970 0.1904 -0.6738 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0363 2.3130 -0.2334 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1103 0.9022 -1.4144 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3599 0.5609 0.2599 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6149 0.6108 1.6073 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7585 -1.4064 0.4356 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1066 -2.9071 -0.3654 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9320 0.5843 -1.2892 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1206 -1.9019 0.1816 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3856 -1.1199 -0.7511 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3094 -2.2164 0.1018 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8166 -1.2453 1.6495 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1437 -0.7621 2.0564 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6153 1.2354 2.1931 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4005 1.3734 0.8750 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1936 0.7257 -0.8218 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6954 2.1296 0.1126 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5254 -0.8103 0.6420 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0318 0.5910 1.6442 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8865 1.6436 -0.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3994 0.1869 -1.3872 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3861 0.1745 0.9173 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9110 -1.2496 -0.0360 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0870 0.1445 -1.4932 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 3 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 1 22 1 0 1 23 1 0 1 24 1 0 2 25 1 0 2 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 5 30 1 0 8 31 1 0 9 32 1 0 12 33 1 0 12 34 1 0 13 35 1 0 13 36 1 0 14 37 1 0 14 38 1 0 15 39 1 0 15 40 1 0 16 41 1 0 16 42 1 0 17 43 1 0 17 44 1 0 18 45 1 0 18 46 1 0 21 47 1 0 M END

Standard InCHIKey	SNUNXDVKYBQMPJ-UZWKOAOVSA-N
Standard InCHI	InChI=1S/C18H26O3/c1-2-3-4-5-6-8-11-14-17(19)15-12-9-7-10-13-16-18(20)21/h4-5,11,14H,2-3,7,9-10,12-13,15-16H2,1H3,(H,20,21)/b5-4-,14-11+
SMILES	CCC/C=CC#C/C=C/C(=O)CCCCCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	290.19	Volume:	330.436 ? Van der Waals volume.
Dense:	0.878	LogP:	4.505 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.146 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.894 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	5.0
TPSA:	54.37 ? 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:	0.351	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.935	Fsp³:	0.556
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:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.036	Fluc inhibitor:	0.016 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.009 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.978	Promiscuous compounds:	0.15

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.074	MDCK Permeability:	-4.877
Pgp-inhibitor:	0.001	Pgp-substrate:	0.002
PAMPA:	0.959 ? 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):	0.175
20% Bioavailability (F20%):	0.019	30% Bioavailability (F30%):	0.042
50% Bioavailability (F50%):	0.712

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.71
Plasma Protein Binding (PPB):	97.684%	Volume Distribution (VD):	-0.59
Fu:	1.656% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.066
OATP1B3 inhibitor:	0.664	BCRP inhibitor:	0.001
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.841
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.978
CYP2C9-inhibitor:	0.972	CYP2C9-substrate:	0.391
CYP2D6-inhibitor:	0.012	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.944
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.048 ? 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):

4.015

Half-life (T1/2):

0.767

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.224
Human Hepatotoxicity (H-HT):	0.481	Drug-induced Liver Injury (DILI):	0.69
AMES Toxicity:	0.143	Rat Oral Acute Toxicity:	0.128
Maximum Recommended Daily Dose:	0.353	Skin Sensitization:	0.787
Carcinogencity:	0.16	Eye Corrosion:	0.988
Eye Irritation:	0.997	Respiratory Toxicity:	0.962
Drug-induced Neurotoxicity:	0.069	Ototoxicity:	0.476
Hematotoxicity:	0.076	Drug-induced Nephrotoxicity:	0.181
Genotoxicity:	0.003	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.012	Hek293 Cytotoxicity:	0.128
BCF:	1.318 ? 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:	4.104 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.381 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.761 ? 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
NPO4561	Cantharellus cibarius	Species	Cantharellaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22342624]
NPO4561	Cantharellus cibarius	Species	Cantharellaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4561	Cantharellus cibarius	Species	Cantharellaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO4561	Cantharellus cibarius	Species	Cantharellaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO4561	Cantharellus cibarius	Species	Cantharellaceae	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
EC50	1
FC	1

Activity Type	# Activity
Cell line	1
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT99	Individual protein	Peroxisome proliferator-activated receptor gamma	Homo sapiens	EC50	=	1880.0	nM	PMID[16562846]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT65	Cell line	HepG2	Homo sapiens	FC	=	2.43	n.a.	PMID[25286284]

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 NPC235242 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	31854
0.1-0.2	17000
0.2-0.3	793
0.3-0.4	102
0.4-0.5	77
0.5-0.6	20
0.6-0.7	8
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
0.6818	Remote Similarity	NPC106851
0.6818	Remote Similarity	NPC282788
0.6818	Remote Similarity	NPC274927
0.6667	Remote Similarity	NPC40082
0.6522	Remote Similarity	NPC251042
0.6522	Remote Similarity	NPC174447
0.6522	Remote Similarity	NPC122521
0.6	Remote Similarity	NPC225929
0.5918	Remote Similarity	NPC470320
0.5745	Remote Similarity	NPC477201
0.5714	Remote Similarity	NPC18712
0.5714	Remote Similarity	NPC74845
0.5625	Remote Similarity	NPC179764
0.56	Remote Similarity	NPC325977
0.551	Remote Similarity	NPC187777
0.5306	Remote Similarity	NPC274290
0.5294	Remote Similarity	NPC143396
0.5238	Remote Similarity	NPC281245
0.5116	Remote Similarity	NPC424
0.5116	Remote Similarity	NPC36061
0.5116	Remote Similarity	NPC69510
0.5116	Remote Similarity	NPC77272
0.5116	Remote Similarity	NPC290563
0.5116	Remote Similarity	NPC139029
0.5116	Remote Similarity	NPC281972
0.5116	Remote Similarity	NPC261831
0.5116	Remote Similarity	NPC87564
0.5102	Remote Similarity	NPC28205

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC235242 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5733
0.1-0.2	3249
0.2-0.3	139
0.3-0.4	16
0.4-0.5	11
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
0.5116	Remote Similarity	NPD3195	Phase 2
0.5116	Remote Similarity	NPD3196	Approved

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