NPASS Compound

Natural Product: NPC536600

Natural Product ID	NPC536600
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Octadeca-5,9,12,15-tetraenoic acid
IUPAC Name	octadeca-5,9,12,15-tetraenoic acid
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 48 47 0 0 0 0 0 0 0 0999 V2000 -6.3699 0.1150 2.0765 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8022 -0.9805 1.2212 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1488 -0.3495 0.0301 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1484 0.9580 -0.1136 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4799 1.5469 -1.3264 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9159 0.5070 -2.1906 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6634 0.4065 -2.4899 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6155 1.3273 -2.0036 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6142 0.5245 -1.2167 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3620 0.7632 0.0402 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5793 0.0649 0.9010 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4269 -1.0048 0.2843 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3874 -0.4936 -0.7175 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6796 -0.6444 -0.5941 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3407 -1.3178 0.5164 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2847 -0.3346 1.2307 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3139 0.1362 0.2399 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2599 1.0838 0.8952 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0896 1.3497 2.1061 O 0 0 0 0 0 0 0 0 0 0 0 0 8.2820 1.6373 0.1722 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.1122 0.7095 1.5437 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7712 -0.3431 3.0147 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5414 0.7691 2.4052 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1085 -1.6368 1.7564 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6211 -1.6243 0.8338 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6678 -0.9677 -0.7252 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5947 1.6595 0.5763 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2719 2.0795 -1.9504 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7932 2.3586 -1.0443 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6246 -0.2303 -2.6083 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3750 -0.4262 -3.1530 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0366 1.6265 -2.9317 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9327 2.2187 -1.4942 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1543 -0.2751 -1.7768 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9268 1.5914 0.5087 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2445 0.7868 1.4567 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0208 -0.4366 1.7565 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7821 -1.7376 -0.2905 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8511 -1.6020 1.0942 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0336 0.0528 -1.6207 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3010 -0.2262 -1.4102 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6959 -1.7094 1.3131 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9742 -2.1863 0.1558 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6488 0.5303 1.5606 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7155 -0.7611 2.1382 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8593 0.7131 -0.5901 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8438 -0.7244 -0.1921 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0376 2.1248 0.6121 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 3 4 5 1 0 5 6 1 0 6 7 2 3 7 8 1 0 8 9 1 0 9 10 2 3 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 3 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 18 20 1 0 1 21 1 0 1 22 1 0 1 23 1 0 2 24 1 0 2 25 1 0 3 26 1 0 4 27 1 0 5 28 1 0 5 29 1 0 6 30 1 0 7 31 1 0 8 32 1 0 8 33 1 0 9 34 1 0 10 35 1 0 11 36 1 0 11 37 1 0 12 38 1 0 12 39 1 0 13 40 1 0 14 41 1 0 15 42 1 0 15 43 1 0 16 44 1 0 16 45 1 0 17 46 1 0 17 47 1 0 20 48 1 0 M END

Standard InCHIKey	DNOBNGNBPVOMLW-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H28O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18(19)20/h3-4,6-7,9-10,13-14H,2,5,8,11-12,15-17H2,1H3,(H,19,20)
SMILES	CCC=CCC=CCC=CCCC=CCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	276.21	Volume:	324.282 ? Van der Waals volume.
Dense:	0.852	LogP:	6.16 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.267 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.443 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	12.0	Rigid Bonds:	5.0
TPSA:	37.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.381	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.907	Fsp³:	0.5
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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.03	Fluc inhibitor:	0.331 ? 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:	0.004 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.998	Promiscuous compounds:	0.527

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.034	MDCK Permeability:	-4.832
Pgp-inhibitor:	0.003	Pgp-substrate:	0.003
PAMPA:	0.576 ? 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):	0.036
20% Bioavailability (F20%):	0.023	30% Bioavailability (F30%):	0.294
50% Bioavailability (F50%):	0.131

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.329	MRP1:	0.961
Plasma Protein Binding (PPB):	97.625%	Volume Distribution (VD):	-0.633
Fu:	2.466% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.222
OATP1B3 inhibitor:	0.574	BCRP inhibitor:	0.01
BSEP inhibitor:	0.398

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.002
CYP2C19-inhibitor:	0.988	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.99	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.003 ? 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):

6.326

Half-life (T1/2):

0.271

ADMET: Toxicity

hERG Blockers:	0.057	hERG Blockers (10um):	0.161
Human Hepatotoxicity (H-HT):	0.145	Drug-induced Liver Injury (DILI):	0.004
AMES Toxicity:	0.423	Rat Oral Acute Toxicity:	0.105
Maximum Recommended Daily Dose:	0.13	Skin Sensitization:	0.998
Carcinogencity:	0.199	Eye Corrosion:	0.982
Eye Irritation:	0.995	Respiratory Toxicity:	0.825
Drug-induced Neurotoxicity:	0.048	Ototoxicity:	0.381
Hematotoxicity:	0.044	Drug-induced Nephrotoxicity:	0.227
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.025
A549 Cytotoxicity:	0.017	Hek293 Cytotoxicity:	0.021
BCF:	1.204 ? 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:	3.809 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.097 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.084 ? 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
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20581114]
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25515814]
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Article]
NPO9262	Chamaecyparis hodginsii	Species	Cupressaceae	Eukaryota	n.a.	seed	n.a.	Database[Article]
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9262	Chamaecyparis hodginsii	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[MetaboLights]
NPO4011	Chlamydomonas reinhardtii	Species	Chlamydomonadaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9262	Chamaecyparis hodginsii	Species	Cupressaceae	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 NPC536600 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	40285
0.1-0.2	8556
0.2-0.3	745
0.3-0.4	167
0.4-0.5	60
0.5-0.6	25
0.6-0.7	11
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9615	High Similarity	NPC117572
0.7667	Intermediate Similarity	NPC149821
0.7419	Intermediate Similarity	NPC91495
0.7419	Intermediate Similarity	NPC70387
0.7188	Intermediate Similarity	NPC52955
0.7188	Intermediate Similarity	NPC88966
0.7188	Intermediate Similarity	NPC25417
0.7188	Intermediate Similarity	NPC1813
0.7188	Intermediate Similarity	NPC59051
0.6389	Remote Similarity	NPC323436
0.6389	Remote Similarity	NPC327388
0.6364	Remote Similarity	NPC321062
0.6364	Remote Similarity	NPC48162
0.6364	Remote Similarity	NPC5413
0.6333	Remote Similarity	NPC270796
0.6176	Remote Similarity	NPC154245
0.6176	Remote Similarity	NPC85813
0.6176	Remote Similarity	NPC223697
0.6176	Remote Similarity	NPC6095
0.6061	Remote Similarity	NPC207292
0.575	Remote Similarity	NPC323597
0.575	Remote Similarity	NPC211752
0.575	Remote Similarity	NPC323498
0.561	Remote Similarity	NPC320305
0.561	Remote Similarity	NPC321838
0.5526	Remote Similarity	NPC284212
0.55	Remote Similarity	NPC477779
0.5476	Remote Similarity	NPC325977
0.5476	Remote Similarity	NPC327112
0.5455	Remote Similarity	NPC281245
0.5349	Remote Similarity	NPC328311
0.5294	Remote Similarity	NPC424
0.5294	Remote Similarity	NPC36061
0.5294	Remote Similarity	NPC69510
0.5294	Remote Similarity	NPC77272
0.5294	Remote Similarity	NPC290563
0.5294	Remote Similarity	NPC139029
0.5294	Remote Similarity	NPC281972
0.5294	Remote Similarity	NPC92114
0.5294	Remote Similarity	NPC261831
0.5294	Remote Similarity	NPC87564
0.5227	Remote Similarity	NPC322461
0.5185	Remote Similarity	NPC174368
0.5111	Remote Similarity	NPC605544
0.5111	Remote Similarity	NPC607260

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC536600 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7021
0.1-0.2	1901
0.2-0.3	170
0.3-0.4	42
0.4-0.5	7
0.5-0.6	3
0.6-0.7	4
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9615	High Similarity	NPD4222	Phase 3
0.7188	Intermediate Similarity	NPD3172	Approved
0.641	Remote Similarity	NPD39	Phase 4
0.6364	Remote Similarity	NPD3173	Phase 4
0.6333	Remote Similarity	NPD5326	Phase 3
0.6176	Remote Similarity	NPD4266	Phase 2
0.5476	Remote Similarity	NPD4246	Phase 2
0.5294	Remote Similarity	NPD3195	Phase 2
0.5294	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