NPASS Compound

Natural Product: NPC536243

Natural Product ID	NPC536243
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	hexadeca-7,10,13-trienoic acid
IUPAC Name	hexadeca-7,10,13-trienoic 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 44 43 0 0 0 0 0 0 0 0999 V2000 6.4078 1.7156 0.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4461 0.8750 -0.1898 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7888 -0.5321 -0.0167 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9912 -1.4470 0.4791 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5904 -1.2074 0.9544 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7309 -2.0760 0.1132 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7886 -1.6471 -0.6594 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4388 -0.2242 -0.8108 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0351 0.0041 -0.3876 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6875 -0.9942 0.0494 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1131 -0.8695 0.5002 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5348 0.5677 0.3601 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9529 0.7176 0.8318 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8697 -0.1284 0.0205 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3054 0.0482 0.4934 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.7987 1.4289 0.3590 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.9441 1.7251 0.8252 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1170 2.4640 -0.2443 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3964 1.3865 1.6857 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1311 2.7867 0.5485 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4531 1.5962 0.2816 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6234 1.1171 -1.2772 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4310 1.1799 0.0356 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7930 -0.8461 -0.3267 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3205 -2.4896 0.5787 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5481 -1.5758 2.0420 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3145 -0.1673 0.9939 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9013 -3.1806 0.1415 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2138 -2.3855 -1.2474 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1325 0.4943 -0.3696 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4042 -0.0668 -1.9501 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3821 0.9895 -0.4440 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2302 -1.9909 0.0956 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6827 -1.4940 -0.2458 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2676 -1.1787 1.5319 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5115 0.8159 -0.7233 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8437 1.2259 0.9397 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9504 0.3182 1.8917 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2651 1.7731 0.9084 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8751 0.1329 -1.0567 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5919 -1.2086 0.0621 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9907 -0.6389 -0.0418 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3075 -0.2306 1.5682 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6589 3.2169 -0.6688 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 1 0 14 15 1 0 15 16 1 0 16 17 2 0 16 18 1 0 1 19 1 0 1 20 1 0 1 21 1 0 2 22 1 0 2 23 1 0 3 24 1 0 4 25 1 0 5 26 1 0 5 27 1 0 6 28 1 0 7 29 1 0 8 30 1 0 8 31 1 0 9 32 1 0 10 33 1 0 11 34 1 0 11 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 13 39 1 0 14 40 1 0 14 41 1 0 15 42 1 0 15 43 1 0 18 44 1 0 M END

Standard InCHIKey	KBGYPXOSNDMZRV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H26O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16(17)18/h3-4,6-7,9-10H,2,5,8,11-15H2,1H3,(H,17,18)
SMILES	CCC=CCC=CCC=CCCCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	250.19	Volume:	292.327 ? Van der Waals volume.
Dense:	0.856	LogP:	5.662 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.166 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.283 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	4.0
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:	0.419	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.632	Fsp³:	0.562
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:	0.011	Fluc inhibitor:	0.305 ? 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:	0.017 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.998	Promiscuous compounds:	0.552

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.066	MDCK Permeability:	-4.826
Pgp-inhibitor:	0.005	Pgp-substrate:	0.006
PAMPA:	0.571 ? 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):	0.063
20% Bioavailability (F20%):	0.065	30% Bioavailability (F30%):	0.36
50% Bioavailability (F50%):	0.14

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.334	MRP1:	0.958
Plasma Protein Binding (PPB):	97.754%	Volume Distribution (VD):	-0.656
Fu:	2.022% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.173
OATP1B3 inhibitor:	0.589	BCRP inhibitor:	0.015
BSEP inhibitor:	0.475

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.145	CYP2C19-substrate:	0.009
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.967	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.0 ? 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):

4.445

Half-life (T1/2):

0.402

ADMET: Toxicity

hERG Blockers:	0.055	hERG Blockers (10um):	0.135
Human Hepatotoxicity (H-HT):	0.099	Drug-induced Liver Injury (DILI):	0.006
AMES Toxicity:	0.447	Rat Oral Acute Toxicity:	0.096
Maximum Recommended Daily Dose:	0.091	Skin Sensitization:	0.998
Carcinogencity:	0.247	Eye Corrosion:	0.98
Eye Irritation:	0.998	Respiratory Toxicity:	0.858
Drug-induced Neurotoxicity:	0.06	Ototoxicity:	0.32
Hematotoxicity:	0.037	Drug-induced Nephrotoxicity:	0.173
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.021
A549 Cytotoxicity:	0.009	Hek293 Cytotoxicity:	0.013
BCF:	1.151 ? 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:	3.741 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.052 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.718 ? 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
NPO31351	Spirodela polyrrhiza	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31351	Spirodela polyrrhiza	Species	Araceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC536243 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	39416
0.1-0.2	9164
0.2-0.3	937
0.3-0.4	170
0.4-0.5	68
0.5-0.6	63
0.6-0.7	7
0.7-0.8	4
0.8-0.85	5
0.85-0.9	2
0.9-0.95	0
0.95-1	5

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC70387
0.9655	High Similarity	NPC52955
0.9655	High Similarity	NPC88966
0.9655	High Similarity	NPC25417
0.9655	High Similarity	NPC1813
0.8966	High Similarity	NPC149821
0.8667	High Similarity	NPC321062
0.8387	Intermediate Similarity	NPC154245
0.8387	Intermediate Similarity	NPC85813
0.8387	Intermediate Similarity	NPC223697
0.8387	Intermediate Similarity	NPC6095
0.8065	Intermediate Similarity	NPC5413
0.7667	Intermediate Similarity	NPC117572
0.7667	Intermediate Similarity	NPC281245
0.75	Intermediate Similarity	NPC91495
0.7419	Intermediate Similarity	NPC424
0.7419	Intermediate Similarity	NPC36061
0.7419	Intermediate Similarity	NPC69510
0.7419	Intermediate Similarity	NPC77272
0.7419	Intermediate Similarity	NPC290563
0.7419	Intermediate Similarity	NPC139029
0.7419	Intermediate Similarity	NPC281972
0.7419	Intermediate Similarity	NPC261831
0.7419	Intermediate Similarity	NPC87564
0.7273	Intermediate Similarity	NPC59051
0.7188	Intermediate Similarity	NPC207292
0.6875	Remote Similarity	NPC92114
0.6667	Remote Similarity	NPC95145
0.6667	Remote Similarity	NPC325642
0.6667	Remote Similarity	NPC65174
0.6053	Remote Similarity	NPC284212
0.6053	Remote Similarity	NPC606120
0.6	Remote Similarity	NPC294548
0.5952	Remote Similarity	NPC320642
0.5952	Remote Similarity	NPC329550
0.5938	Remote Similarity	NPC180534
0.5938	Remote Similarity	NPC270796
0.5938	Remote Similarity	NPC611531
0.5854	Remote Similarity	NPC323597
0.5854	Remote Similarity	NPC211752
0.5854	Remote Similarity	NPC323498
0.5814	Remote Similarity	NPC323045
0.5814	Remote Similarity	NPC317881
0.575	Remote Similarity	NPC477201
0.5714	Remote Similarity	NPC317583
0.5714	Remote Similarity	NPC268826
0.5682	Remote Similarity	NPC322461
0.5667	Remote Similarity	NPC155263
0.5641	Remote Similarity	NPC225929
0.5588	Remote Similarity	NPC34416
0.5556	Remote Similarity	NPC48162
0.5556	Remote Similarity	NPC605544
0.5556	Remote Similarity	NPC607260
0.5517	Remote Similarity	NPC214610
0.5517	Remote Similarity	NPC118968
0.5517	Remote Similarity	NPC183424
0.5517	Remote Similarity	NPC294085
0.5484	Remote Similarity	NPC171736
0.5484	Remote Similarity	NPC301585
0.5484	Remote Similarity	NPC261080
0.5484	Remote Similarity	NPC132565
0.5484	Remote Similarity	NPC209970
0.5484	Remote Similarity	NPC216630
0.5484	Remote Similarity	NPC201844
0.5484	Remote Similarity	NPC301696
0.5484	Remote Similarity	NPC196924
0.5484	Remote Similarity	NPC307783
0.5484	Remote Similarity	NPC154186
0.5484	Remote Similarity	NPC149184
0.5484	Remote Similarity	NPC279026
0.5484	Remote Similarity	NPC113928
0.5484	Remote Similarity	NPC14227
0.5476	Remote Similarity	NPC243532
0.5476	Remote Similarity	NPC473863
0.5435	Remote Similarity	NPC329249
0.5435	Remote Similarity	NPC92558
0.5366	Remote Similarity	NPC106851
0.5366	Remote Similarity	NPC282788
0.5366	Remote Similarity	NPC274927
0.5349	Remote Similarity	NPC68343
0.5349	Remote Similarity	NPC328089
0.5333	Remote Similarity	NPC175342
0.525	Remote Similarity	NPC323436
0.525	Remote Similarity	NPC327388
0.5238	Remote Similarity	NPC179764
0.5227	Remote Similarity	NPC325977
0.5227	Remote Similarity	NPC327112
0.5172	Remote Similarity	NPC134782
0.5135	Remote Similarity	NPC224227
0.5116	Remote Similarity	NPC251042
0.5116	Remote Similarity	NPC255863
0.5116	Remote Similarity	NPC174447
0.5116	Remote Similarity	NPC136164
0.5116	Remote Similarity	NPC122521
0.5116	Remote Similarity	NPC245947
0.5111	Remote Similarity	NPC328311

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC536243 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6944
0.1-0.2	1966
0.2-0.3	185
0.3-0.4	32
0.4-0.5	8
0.5-0.6	7
0.6-0.7	1
0.7-0.8	4
0.8-0.85	2
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9655	High Similarity	NPD3172	Approved
0.8387	Intermediate Similarity	NPD4266	Phase 2
0.8065	Intermediate Similarity	NPD3173	Phase 4
0.7667	Intermediate Similarity	NPD4222	Phase 3
0.7419	Intermediate Similarity	NPD3195	Phase 2
0.7419	Intermediate Similarity	NPD3196	Approved
0.7368	Intermediate Similarity	NPD39	Phase 4
0.6053	Remote Similarity	NPD3194	Phase 4
0.5938	Remote Similarity	NPD5326	Phase 3
0.5938	Remote Similarity	NPD622	Pre-clinical
0.5517	Remote Similarity	NPD9655	Phase 4
0.5484	Remote Similarity	NPD2270	Pre-clinical
0.5484	Remote Similarity	NPD633	Phase 3
0.5484	Remote Similarity	NPD9448	Phase 2
0.5227	Remote Similarity	NPD4246	Phase 2

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