NPASS Compound

Natural Product: NPC476654

Natural Product ID	NPC476654
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 (5E,7E)-octadeca-5,7-dienoate
IUPAC Name	2,3-dihydroxypropyl (5E,7E)-octadeca-5,7-dienoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	76316612
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 63 62 0 0 0 0 0 0 0 0999 V2000 -9.8149 1.2270 0.7576 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4086 1.0109 0.2154 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3607 -0.3922 -0.3146 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9905 -0.7670 -0.8895 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6341 0.1264 -2.0115 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3917 -0.0903 -2.7465 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0633 0.0213 -2.1523 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6310 -0.8617 -1.0532 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1557 -0.5625 -0.6813 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8348 -1.5224 0.4436 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4519 -1.3248 0.8752 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3220 -0.4184 0.3062 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6946 -0.2994 0.8130 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5367 0.5812 0.3018 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9371 0.7794 0.7406 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2580 -0.1665 1.8442 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6340 -0.0877 2.3997 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6610 -0.3765 1.3750 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3767 -0.6688 0.2027 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9832 -0.3024 1.7996 O 0 0 0 0 0 0 0 0 0 0 0 0 9.0572 -0.5442 0.9538 C 0 0 0 0 0 0 0 0 0 0 0 0 9.0474 0.4485 -0.1810 C 0 0 0 0 0 0 0 0 0 0 0 0 9.1675 1.8265 0.4352 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2425 2.8367 -0.4947 O 0 0 0 0 0 0 0 0 0 0 0 0 10.1485 0.1600 -0.9920 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.8208 1.9860 1.5660 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.4971 1.5481 -0.0813 H 0 0 0 0 0 0 0 0 0 0 0 0 -10.1920 0.2534 1.1273 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1933 1.7803 -0.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7134 1.1469 1.0439 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6462 -1.0719 0.5009 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1413 -0.4930 -1.1086 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1366 -1.7995 -1.3071 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2700 -0.7899 -0.0634 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4788 0.0856 -2.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6325 1.2167 -1.6669 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4153 0.6572 -3.6318 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4730 -1.0815 -3.3438 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2389 -0.0052 -2.9573 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9517 1.0887 -1.7437 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1526 -0.7574 -0.1009 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6449 -1.9165 -1.3695 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0493 0.4585 -0.3021 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4949 -0.7796 -1.5216 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5638 -1.2854 1.2635 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0606 -2.5719 0.1544 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0696 -1.9482 1.6852 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0377 0.2035 -0.4920 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0391 -0.9281 1.6117 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1125 1.1922 -0.5141 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6458 0.8175 -0.0934 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9562 1.8145 1.2013 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0338 -1.1955 1.4643 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4994 0.0170 2.6545 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7319 -0.8622 3.1817 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7776 0.9065 2.8712 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0913 -1.5886 0.5677 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9963 -0.3302 1.5399 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1654 0.3663 -0.8317 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2956 1.9528 1.1102 H 0 0 0 0 0 0 0 0 0 0 0 0 10.0863 1.8290 1.0694 H 0 0 0 0 0 0 0 0 0 0 0 0 9.4827 2.5179 -1.4038 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6312 -0.6294 -0.6943 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 22 25 1 0 1 26 1 0 1 27 1 0 1 28 1 0 2 29 1 0 2 30 1 0 3 31 1 0 3 32 1 0 4 33 1 0 4 34 1 0 5 35 1 0 5 36 1 0 6 37 1 0 6 38 1 0 7 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 9 43 1 0 9 44 1 0 10 45 1 0 10 46 1 0 11 47 1 0 12 48 1 0 13 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 17 56 1 0 21 57 1 0 21 58 1 0 22 59 1 0 23 60 1 0 23 61 1 0 24 62 1 0 25 63 1 0 M END

Standard InCHIKey	VIJAZCBOAKGHAD-LDHFCIDVSA-N
Standard InCHI	InChI=1S/C21H38O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-21(24)25-19-20(23)18-22/h11-14,20,22-23H,2-10,15-19H2,1H3/b12-11+,14-13+
SMILES	CCCCCCCCCC/C=C/C=C/CCCC(=O)OCC(CO)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	354.28	Volume:	399.024 ? Van der Waals volume.
Dense:	0.888	LogP:	4.463 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.647 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.366 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	18.0	Rigid Bonds:	3.0
TPSA:	66.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	0.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.226	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.982	Fsp³:	0.762
MCE-18:	2.0 ? 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:	0.317	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:	0.01 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.896	Promiscuous compounds:	0.219

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.073	MDCK Permeability:	-4.709
Pgp-inhibitor:	0.0	Pgp-substrate:	0.492
PAMPA:	0.033 ? 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):	0.123
20% Bioavailability (F20%):	0.972	30% Bioavailability (F30%):	0.995
50% Bioavailability (F50%):	0.985

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.4
Plasma Protein Binding (PPB):	98.033%	Volume Distribution (VD):	-0.348
Fu:	1.172% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.036
OATP1B3 inhibitor:	0.998	BCRP inhibitor:	0.494
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.947
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.988	CYP2C9-substrate:	0.38
CYP2D6-inhibitor:	0.996	CYP2D6-substrate:	0.881
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.412 ? 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):

4.953

Half-life (T1/2):

0.664

ADMET: Toxicity

hERG Blockers:	0.206	hERG Blockers (10um):	0.545
Human Hepatotoxicity (H-HT):	0.348	Drug-induced Liver Injury (DILI):	0.018
AMES Toxicity:	0.532	Rat Oral Acute Toxicity:	0.018
Maximum Recommended Daily Dose:	0.105	Skin Sensitization:	0.995
Carcinogencity:	0.273	Eye Corrosion:	0.05
Eye Irritation:	0.735	Respiratory Toxicity:	0.084
Drug-induced Neurotoxicity:	0.032	Ototoxicity:	0.799
Hematotoxicity:	0.084	Drug-induced Nephrotoxicity:	0.554
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.033
A549 Cytotoxicity:	0.1	Hek293 Cytotoxicity:	0.109
BCF:	1.44 ? 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:	4.984 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.314 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.733 ? 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
NPO33615	Aspergillus sp. MF-93	Species	Aspergillaceae	Eukaryota	n.a.	Quan-Zhou Gulf, Fujian Province, China	2002	PMID[18823067]
NPO33615	Aspergillus sp. MF-93	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Organism	1

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
NPT786	Organism	Tobacco mosaic virus	Tobacco mosaic virus	Inhibition	=	12.5	%	PMID[18823067]

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 NPC476654 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	15669
0.1-0.2	30024
0.2-0.3	3534
0.3-0.4	520
0.4-0.5	74
0.5-0.6	16
0.6-0.7	6
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC476655
1.0	High Similarity	NPC476656
0.8333	Intermediate Similarity	NPC104537
0.7895	Intermediate Similarity	NPC321919
0.7692	Intermediate Similarity	NPC330426
0.7692	Intermediate Similarity	NPC127091
0.7692	Intermediate Similarity	NPC22101
0.75	Intermediate Similarity	NPC474321
0.725	Intermediate Similarity	NPC209327
0.7143	Intermediate Similarity	NPC488257
0.7143	Intermediate Similarity	NPC469937
0.7143	Intermediate Similarity	NPC94699
0.7143	Intermediate Similarity	NPC320588
0.7143	Intermediate Similarity	NPC53463
0.7073	Intermediate Similarity	NPC273508
0.6829	Remote Similarity	NPC271921
0.6667	Remote Similarity	NPC277597
0.6341	Remote Similarity	NPC476657
0.6341	Remote Similarity	NPC476659
0.619	Remote Similarity	NPC475443
0.619	Remote Similarity	NPC473829
0.5952	Remote Similarity	NPC476660
0.5789	Remote Similarity	NPC128061
0.5789	Remote Similarity	NPC228473
0.5778	Remote Similarity	NPC48218
0.5778	Remote Similarity	NPC141481
0.5778	Remote Similarity	NPC464342
0.575	Remote Similarity	NPC609455
0.5714	Remote Similarity	NPC485026
0.5652	Remote Similarity	NPC473772
0.5455	Remote Similarity	NPC476658
0.5417	Remote Similarity	NPC473559
0.5417	Remote Similarity	NPC324981
0.5366	Remote Similarity	NPC223677
0.5366	Remote Similarity	NPC28779
0.5128	Remote Similarity	NPC26253
0.5116	Remote Similarity	NPC148192

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC476654 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6020
0.1-0.2	2918
0.2-0.3	182
0.3-0.4	25
0.4-0.5	4
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
0.5556	Remote Similarity	NPD3728	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