NPASS Compound

Natural Product: NPC598498

Natural Product ID	NPC598498
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 hexadeca-9,12-dienoate
IUPAC Name	2,3-dihydroxypropyl hexadeca-9,12-dienoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000175] Glycerolipids [CHEMONTID:0003808] Monoradylglycerols [CHEMONTID:0001133] Monoacylglycerols [CHEMONTID:0001597] 1-monoacylglycerols

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 57 56 0 0 0 0 0 0 0 0999 V2000 7.1930 1.8201 2.3691 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7136 0.8920 1.2704 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6718 1.6384 -0.0664 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2080 0.7132 -1.1004 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1371 0.9022 -1.8132 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1831 2.0361 -1.7532 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8310 1.4945 -1.4097 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6282 0.2090 -1.2122 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2831 -0.2946 -0.8754 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7763 -1.2844 -1.9007 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5946 -1.8121 -1.5850 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6484 -2.5306 -0.2625 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0334 -3.0625 0.0349 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0413 -1.9649 0.0889 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7225 -0.9605 1.1495 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7611 0.1199 1.1639 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6363 1.0262 0.3187 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7988 0.1565 2.0276 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8366 1.0279 2.1855 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9077 1.1036 1.1454 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8512 2.1081 1.5230 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4843 1.4324 -0.2449 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.6886 1.4749 -1.0250 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3743 1.2521 3.3020 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1188 2.3649 2.0606 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4287 2.5905 2.5968 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6780 0.5771 1.4813 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3873 0.0336 1.1694 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7118 1.9956 -0.3130 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0013 2.4954 0.0458 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7815 -0.2195 -1.3173 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8690 0.1420 -2.5754 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1409 2.4536 -2.8117 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4772 2.8650 -1.1038 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0039 2.1795 -1.3225 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4338 -0.5065 -1.2898 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5750 0.5333 -0.8172 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3965 -0.8406 0.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5273 -2.1074 -1.9804 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8096 -0.7619 -2.8780 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2705 -0.9215 -1.5726 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9590 -2.4403 -2.4223 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3179 -1.8269 0.5254 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0375 -3.3907 -0.2165 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9635 -3.5312 1.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2573 -3.8219 -0.7223 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0326 -2.4191 0.3762 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1102 -1.5057 -0.9304 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6920 -1.4981 2.1198 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7656 -0.4684 0.9638 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3484 0.7515 3.1691 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4985 2.0900 2.3966 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5153 0.1446 1.1684 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.7271 1.7272 1.7125 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9253 2.3565 -0.3088 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9424 0.5670 -0.7334 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0472 0.5555 -0.9499 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 3 5 6 1 0 6 7 1 0 7 8 2 3 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 20 22 1 0 22 23 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 0 2 28 1 0 3 29 1 0 3 30 1 0 4 31 1 0 5 32 1 0 6 33 1 0 6 34 1 0 7 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 12 43 1 0 12 44 1 0 13 45 1 0 13 46 1 0 14 47 1 0 14 48 1 0 15 49 1 0 15 50 1 0 19 51 1 0 19 52 1 0 20 53 1 0 21 54 1 0 22 55 1 0 22 56 1 0 23 57 1 0 M END

Standard InCHIKey	UYILNCYYYVUPEC-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C19H34O4/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-19(22)23-17-18(21)16-20/h4-5,7-8,18,20-21H,2-3,6,9-17H2,1H3
SMILES	CCCC=CCC=CCCCCCCCC(=O)OCC(O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	326.25	Volume:	364.432 ? Van der Waals volume.
Dense:	0.895	LogP:	4.136 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.296 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.544 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	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:	0.272	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.021	Fsp³:	0.737
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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.028	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.004 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.001 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.919	Promiscuous compounds:	0.044

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.057	MDCK Permeability:	-4.879
Pgp-inhibitor:	0.0	Pgp-substrate:	0.094
PAMPA:	0.342 ? 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):	0.133
20% Bioavailability (F20%):	0.476	30% Bioavailability (F30%):	0.692
50% Bioavailability (F50%):	0.822

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.098	MRP1:	0.926
Plasma Protein Binding (PPB):	97.371%	Volume Distribution (VD):	-0.375
Fu:	3.168% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.031
OATP1B3 inhibitor:	0.872	BCRP inhibitor:	0.133
BSEP inhibitor:	0.77

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.622
CYP2C19-inhibitor:	0.001	CYP2C19-substrate:	0.001
CYP2C9-inhibitor:	0.984	CYP2C9-substrate:	0.001
CYP2D6-inhibitor:	0.835	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.997
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.407 ? 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):

5.652

Half-life (T1/2):

0.504

ADMET: Toxicity

hERG Blockers:	0.067	hERG Blockers (10um):	0.394
Human Hepatotoxicity (H-HT):	0.104	Drug-induced Liver Injury (DILI):	0.001
AMES Toxicity:	0.616	Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.019	Skin Sensitization:	1.0
Carcinogencity:	0.259	Eye Corrosion:	0.629
Eye Irritation:	0.938	Respiratory Toxicity:	0.043
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.691
Hematotoxicity:	0.011	Drug-induced Nephrotoxicity:	0.349
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.061	Hek293 Cytotoxicity:	0.021
BCF:	1.649 ? 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:	4.681 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.062 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.909 ? 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
NPO28907	Sonchus arvensis	Species	Asteraceae	Eukaryota	n.a	The rural area of ViÃƒÂ§osa, State of Minas Gerais (MG), Brazil	Adult stage	PMID[35282307]
NPO28907	Sonchus arvensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28907	Sonchus arvensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28907	Sonchus arvensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28907	Sonchus arvensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28907	Sonchus arvensis	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 NPC598498 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	15766
0.1-0.2	30519
0.2-0.3	3053
0.3-0.4	416
0.4-0.5	57
0.5-0.6	14
0.6-0.7	20
0.7-0.8	0
0.8-0.85	0
0.85-0.9	3
0.9-0.95	3
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9444	High Similarity	NPC330426
0.9444	High Similarity	NPC127091
0.9444	High Similarity	NPC22101
0.8919	High Similarity	NPC271921
0.8649	High Similarity	NPC321919
0.8611	High Similarity	NPC104537
0.7692	Intermediate Similarity	NPC475443
0.7692	Intermediate Similarity	NPC473829
0.725	Intermediate Similarity	NPC476654
0.725	Intermediate Similarity	NPC476655
0.725	Intermediate Similarity	NPC476656
0.7073	Intermediate Similarity	NPC209327
0.6944	Remote Similarity	NPC488257
0.6944	Remote Similarity	NPC469937
0.6944	Remote Similarity	NPC94699
0.6944	Remote Similarity	NPC320588
0.6944	Remote Similarity	NPC53463
0.6923	Remote Similarity	NPC277597
0.6905	Remote Similarity	NPC273508
0.6842	Remote Similarity	NPC28779
0.6667	Remote Similarity	NPC473559
0.6667	Remote Similarity	NPC324981
0.6591	Remote Similarity	NPC473772
0.641	Remote Similarity	NPC10316
0.641	Remote Similarity	NPC200845
0.625	Remote Similarity	NPC474321
0.6136	Remote Similarity	NPC54925
0.6053	Remote Similarity	NPC128061
0.6	Remote Similarity	NPC48218
0.6	Remote Similarity	NPC141481
0.6	Remote Similarity	NPC464342
0.6	Remote Similarity	NPC609455
0.5926	Remote Similarity	NPC489083
0.5897	Remote Similarity	NPC39633
0.561	Remote Similarity	NPC223677
0.5517	Remote Similarity	NPC21693
0.55	Remote Similarity	NPC139545
0.5455	Remote Similarity	NPC81896
0.5385	Remote Similarity	NPC26253
0.5349	Remote Similarity	NPC148192
0.5333	Remote Similarity	NPC110813
0.5333	Remote Similarity	NPC39290
0.5254	Remote Similarity	NPC236649
0.5227	Remote Similarity	NPC485026
0.5128	Remote Similarity	NPC309606
0.5122	Remote Similarity	NPC71761

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC598498 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6131
0.1-0.2	2836
0.2-0.3	154
0.3-0.4	23
0.4-0.5	3
0.5-0.6	3
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
0.55	Remote Similarity	NPD5343	Phase 4
0.5435	Remote Similarity	NPD3728	Approved
0.5238	Remote Similarity	NPD6096	Phase 4

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