NPASS Compound

Natural Product: NPC474321

Natural Product ID	NPC474321
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2,3-Dihydroxypropyl (9E,11E)-13-Oxooctadeca-9,11-Dienoate
IUPAC Name	2,3-dihydroxypropyl (9E,11E)-13-oxooctadeca-9,11-dienoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL465241
PubChem CID	10237201
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000504] Lineolic acids and derivatives

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 62 61 0 0 0 0 0 0 0 0999 V2000 -7.3111 3.2962 0.8888 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0949 1.7996 0.7164 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7160 1.2466 2.0687 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4810 -0.2274 2.0461 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3922 -0.6516 1.1272 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0584 -0.0948 1.4294 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8944 0.6913 2.3809 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.8940 -0.4515 0.6213 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9593 -1.2703 -0.4027 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7457 -1.5705 -1.1523 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7548 -2.3880 -2.1929 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6443 -2.7915 -3.0339 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7270 -2.3082 -2.6394 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1555 -2.9192 -1.3487 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4654 -2.4588 -0.8605 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5616 -1.0725 -0.3769 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2263 0.0811 -1.2194 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5712 1.3659 -0.4215 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0079 1.4782 -0.1314 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3838 2.4078 0.6529 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0164 0.6858 -0.6179 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3496 0.8920 -0.2787 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6637 0.8268 1.1876 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1972 0.9141 1.2837 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5655 2.1407 0.7505 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3295 -0.4064 1.7191 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0622 3.7881 -0.0731 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3756 3.4348 1.1773 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6720 3.6398 1.7193 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9811 1.2820 0.3301 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2915 1.6757 -0.0311 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9170 1.8107 2.5426 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6226 1.4042 2.7230 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.3907 -0.8008 1.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2363 -0.5701 3.0901 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3004 -1.7724 1.1949 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7046 -0.4277 0.0786 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9098 -0.0315 0.8570 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9030 -1.7108 -0.6790 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8266 -1.0948 -0.8790 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7739 -2.7876 -2.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5581 -3.9059 -3.1594 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8754 -2.4390 -4.0835 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8603 -1.2483 -2.7585 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4045 -2.8466 -3.4239 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4117 -2.8688 -0.5184 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2830 -4.0627 -1.5720 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2843 -2.6736 -1.6335 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7547 -3.1944 -0.0195 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0597 -0.9788 0.6572 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6541 -0.9364 -0.0601 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7553 0.0663 -2.1686 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1105 0.2348 -1.3439 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2934 2.1982 -1.0905 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0092 1.3477 0.5183 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9908 0.0925 -0.7624 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7440 1.8482 -0.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3011 1.6930 1.7700 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4265 0.9093 2.3726 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5827 0.0480 0.7475 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9263 2.8516 0.9149 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2743 -0.3575 2.7159 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 2 0 9 10 1 0 10 11 2 0 11 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 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 23 26 1 0 1 27 1 0 1 28 1 0 1 29 1 0 2 30 1 0 2 31 1 0 3 32 1 0 3 33 1 0 4 34 1 0 4 35 1 0 5 36 1 0 5 37 1 0 8 38 1 0 9 39 1 0 10 40 1 0 11 41 1 0 12 42 1 0 12 43 1 0 13 44 1 0 13 45 1 0 14 46 1 0 14 47 1 0 15 48 1 0 15 49 1 0 16 50 1 0 16 51 1 0 17 52 1 0 17 53 1 0 18 54 1 0 18 55 1 0 22 56 1 0 22 57 1 0 23 58 1 0 24 59 1 0 24 60 1 0 25 61 1 0 26 62 1 0 M END

Standard InCHIKey	BABFYBAGZXSUDH-KDFHGORWSA-N
Standard InCHI	InChI=1S/C21H36O5/c1-2-3-11-14-19(23)15-12-9-7-5-4-6-8-10-13-16-21(25)26-18-20(24)17-22/h7,9,12,15,20,22,24H,2-6,8,10-11,13-14,16-18H2,1H3/b9-7+,15-12+
SMILES	CCCCCC(=O)/C=C/C=C/CCCCCCCC(=O)OCC(CO)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.26	Volume:	405.177 ? Van der Waals volume.
Dense:	0.909	LogP:	3.042 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.836 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.746 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	4.0
TPSA:	83.83 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	2.0	Rings:	0.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.176	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.063	Fsp³:	0.714
MCE-18:	3.0 ? 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:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.171	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.043 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.769	Promiscuous compounds:	0.253

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.12	MDCK Permeability:	-4.618
Pgp-inhibitor:	0.0	Pgp-substrate:	0.174
PAMPA:	0.699 ? 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):	0.019
20% Bioavailability (F20%):	0.743	30% Bioavailability (F30%):	0.883
50% Bioavailability (F50%):	0.935

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.245
Plasma Protein Binding (PPB):	94.43%	Volume Distribution (VD):	-0.504
Fu:	6.156% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.026
OATP1B3 inhibitor:	0.979	BCRP inhibitor:	0.017
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.699
CYP2C9-inhibitor:	0.219	CYP2C9-substrate:	0.719
CYP2D6-inhibitor:	0.903	CYP2D6-substrate:	0.988
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.727 ? 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):

5.192

Half-life (T1/2):

0.657

ADMET: Toxicity

hERG Blockers:	0.165	hERG Blockers (10um):	0.437
Human Hepatotoxicity (H-HT):	0.376	Drug-induced Liver Injury (DILI):	0.042
AMES Toxicity:	0.566	Rat Oral Acute Toxicity:	0.021
Maximum Recommended Daily Dose:	0.114	Skin Sensitization:	0.988
Carcinogencity:	0.325	Eye Corrosion:	0.034
Eye Irritation:	0.729	Respiratory Toxicity:	0.067
Drug-induced Neurotoxicity:	0.052	Ototoxicity:	0.728
Hematotoxicity:	0.097	Drug-induced Nephrotoxicity:	0.669
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.037
A549 Cytotoxicity:	0.048	Hek293 Cytotoxicity:	0.109
BCF:	1.316 ? 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:	4.695 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.193 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.843 ? 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
NPO33018	clitocybe clavipes	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12444711]

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
Inhibition	1

Activity Type	# Activity
Individual protein	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6555	Individual protein	Aldehyde dehydrogenase 1, mitochondrial	Saccharomyces cerevisiae	Inhibition	<	50.0	%	PMID[21456549]

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 NPC474321 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	14606
0.1-0.2	32078
0.2-0.3	2771
0.3-0.4	333
0.4-0.5	38
0.5-0.6	13
0.6-0.7	11
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
0.75	Intermediate Similarity	NPC476654
0.75	Intermediate Similarity	NPC476655
0.75	Intermediate Similarity	NPC476656
0.7045	Intermediate Similarity	NPC104537
0.6596	Remote Similarity	NPC330426
0.6596	Remote Similarity	NPC127091
0.6596	Remote Similarity	NPC22101
0.6383	Remote Similarity	NPC143857
0.6383	Remote Similarity	NPC229252
0.6047	Remote Similarity	NPC488257
0.6047	Remote Similarity	NPC469937
0.6047	Remote Similarity	NPC94699
0.6047	Remote Similarity	NPC320588
0.6047	Remote Similarity	NPC53463
0.6042	Remote Similarity	NPC321919
0.5918	Remote Similarity	NPC271921
0.5745	Remote Similarity	NPC277597
0.56	Remote Similarity	NPC209327
0.549	Remote Similarity	NPC273508
0.5472	Remote Similarity	NPC83965
0.54	Remote Similarity	NPC475443
0.54	Remote Similarity	NPC473829
0.5283	Remote Similarity	NPC176215
0.5283	Remote Similarity	NPC296436
0.52	Remote Similarity	NPC476660
0.5094	Remote Similarity	NPC48218
0.5094	Remote Similarity	NPC141481
0.5094	Remote Similarity	NPC464342

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474321 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5783
0.1-0.2	3198
0.2-0.3	153
0.3-0.4	14
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