NPASS Compound

Natural Product: NPC588788

Natural Product ID	NPC588788
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MG(18:4(6Z,9Z,12Z,15Z)/0:0/0:0)
IUPAC Name	[(2~{S})-2,3-dihydroxypropyl] (6~{Z},9~{Z},12~{Z},15~{Z})-octadeca-6,9,12,15-tetraenoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 59 58 0 0 0 0 0 0 0 0999 V2000 5.0193 2.0943 1.8283 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5236 1.0091 0.8522 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0449 -0.0661 1.6804 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6182 -1.2782 1.6727 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5059 -1.7333 0.7841 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0501 -2.7843 -0.0523 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0917 -2.7425 -1.3365 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5899 -1.6240 -2.1203 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5454 -2.1541 -3.0232 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3184 -1.7714 -3.0533 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7952 -0.7126 -2.1532 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2300 0.4197 -2.9194 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0086 0.7861 -2.8069 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9999 0.1526 -1.9319 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5095 1.2180 -0.9400 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5065 0.6154 0.0007 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0413 1.6181 0.9696 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0133 0.9530 1.8871 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6230 0.5652 3.0241 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3195 0.7738 1.4722 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.2550 0.1334 2.3427 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5970 0.0591 1.6134 C 0 0 1 0 0 0 0 0 0 0 0 0 -8.5365 -0.5513 2.4129 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.0447 1.4298 1.2248 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0489 1.9863 0.4229 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5194 1.5412 2.6468 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8806 2.7016 2.1870 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2874 2.6950 1.2847 H 0 0 0 0 0 0 0 0 0 0 0 0 6.3941 1.4975 0.3448 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7011 0.8036 0.1854 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8784 0.1634 2.3749 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0372 -2.0817 2.3192 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9139 -0.9674 0.3387 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7941 -2.2576 1.5158 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4476 -3.6685 0.4952 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5284 -3.5875 -1.9166 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3993 -0.7008 -1.6177 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4495 -1.3625 -2.8414 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8972 -2.9582 -3.7257 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6389 -2.2610 -3.7866 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5366 -0.3551 -1.4050 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0059 -1.1909 -1.5549 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9474 0.9311 -3.5965 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3119 1.6470 -3.4359 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8937 -0.1369 -2.5867 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7269 -0.7483 -1.4252 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6200 1.5141 -0.3598 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9349 2.0284 -1.5485 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0490 -0.2436 0.5411 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3722 0.2436 -0.5930 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2070 2.0280 1.5632 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5924 2.3930 0.4074 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8942 -0.8878 2.5788 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3323 0.7211 3.2529 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4177 -0.5338 0.6786 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.3773 -0.6644 1.9067 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.9584 1.3776 0.6026 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1910 2.0819 2.1092 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2069 1.8421 -0.5344 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 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 22 24 1 0 24 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 4 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 7 36 1 0 8 37 1 0 8 38 1 0 9 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 12 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 15 48 1 0 16 49 1 0 16 50 1 0 17 51 1 0 17 52 1 0 21 53 1 0 21 54 1 0 22 55 1 6 23 56 1 0 24 57 1 0 24 58 1 0 25 59 1 0 M END

Standard InCHIKey	YICVZGXPPMTJCG-LIYQNMAISA-N
Standard InCHI	InChI=1S/C21H34O4/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/h3-4,6-7,9-10,12-13,20,22-23H,2,5,8,11,14-19H2,1H3/b4-3-,7-6-,10-9-,13-12-/t20-/m0/s1
SMILES	CC/C=CC/C=CC/C=CC/C=CCCCCC(=O)OC[C@@H](O)CO

Calculated Properties

Physi-Chem Properties

Molecular Weight:	350.25	Volume:	393.751 ? Van der Waals volume.
Dense:	0.89	LogP:	4.886 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.378 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.041 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	5.0
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:	0.263	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.419	Fsp³:	0.571
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:	0.107	Fluc inhibitor:	0.028 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.005 ? 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:	0.761	Promiscuous compounds:	0.244

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.046	MDCK Permeability:	-4.781
Pgp-inhibitor:	0.016	Pgp-substrate:	0.003
PAMPA:	0.058 ? 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):	0.001
20% Bioavailability (F20%):	0.12	30% Bioavailability (F30%):	0.121
50% Bioavailability (F50%):	0.943

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.179	MRP1:	0.985
Plasma Protein Binding (PPB):	96.991%	Volume Distribution (VD):	-0.264
Fu:	4.276% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.01
OATP1B3 inhibitor:	0.238	BCRP inhibitor:	0.521
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.053
CYP2C19-inhibitor:	0.01	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.053 ? 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):

6.471

Half-life (T1/2):

0.362

ADMET: Toxicity

hERG Blockers:	0.187	hERG Blockers (10um):	0.231
Human Hepatotoxicity (H-HT):	0.001	Drug-induced Liver Injury (DILI):	0.0
AMES Toxicity:	0.973	Rat Oral Acute Toxicity:	0.002
Maximum Recommended Daily Dose:	0.0	Skin Sensitization:	1.0
Carcinogencity:	0.0	Eye Corrosion:	1.0
Eye Irritation:	1.0	Respiratory Toxicity:	0.223
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.092
Hematotoxicity:	0.0	Drug-induced Nephrotoxicity:	0.455
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.009
A549 Cytotoxicity:	0.013	Hek293 Cytotoxicity:	0.0
BCF:	1.606 ? 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:	4.527 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.903 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.06 ? 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
NPO59665	Sargassum sagamianum	Species	Sargassaceae	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

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 NPC588788 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	15656
0.1-0.2	31119
0.2-0.3	2767
0.3-0.4	238
0.4-0.5	34
0.5-0.6	15
0.6-0.7	15
0.7-0.8	0
0.8-0.85	1
0.85-0.9	3
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9714	High Similarity	NPC271921
0.8649	High Similarity	NPC330426
0.8649	High Similarity	NPC127091
0.8649	High Similarity	NPC22101
0.8378	Intermediate Similarity	NPC321919
0.7838	Intermediate Similarity	NPC104537
0.7143	Intermediate Similarity	NPC473772
0.7027	Intermediate Similarity	NPC10316
0.7027	Intermediate Similarity	NPC200845
0.7	Intermediate Similarity	NPC475443
0.7	Intermediate Similarity	NPC473829
0.6829	Remote Similarity	NPC209327
0.6667	Remote Similarity	NPC273508
0.6585	Remote Similarity	NPC476654
0.6585	Remote Similarity	NPC476655
0.6585	Remote Similarity	NPC476656
0.625	Remote Similarity	NPC277597
0.6216	Remote Similarity	NPC488257
0.6216	Remote Similarity	NPC469937
0.6216	Remote Similarity	NPC94699
0.6216	Remote Similarity	NPC320588
0.6216	Remote Similarity	NPC53463
0.6154	Remote Similarity	NPC28779
0.6087	Remote Similarity	NPC473559
0.6087	Remote Similarity	NPC324981
0.6053	Remote Similarity	NPC139545
0.575	Remote Similarity	NPC609455
0.5714	Remote Similarity	NPC474321
0.5614	Remote Similarity	NPC236649
0.5556	Remote Similarity	NPC54925
0.5455	Remote Similarity	NPC489083
0.5435	Remote Similarity	NPC48218
0.5435	Remote Similarity	NPC141481
0.5435	Remote Similarity	NPC464342
0.5424	Remote Similarity	NPC110813
0.5385	Remote Similarity	NPC128061
0.525	Remote Similarity	NPC39633
0.5227	Remote Similarity	NPC81896
0.5167	Remote Similarity	NPC133377
0.5161	Remote Similarity	NPC38295
0.5085	Remote Similarity	NPC21693

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC588788 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6072
0.1-0.2	2933
0.2-0.3	128
0.3-0.4	12
0.4-0.5	2
0.5-0.6	1
0.6-0.7	2
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
0.6486	Remote Similarity	NPD5343	Phase 4
0.6154	Remote Similarity	NPD6096	Phase 4
0.5526	Remote Similarity	NPD6097	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