NPASS Compound

Natural Product: NPC471313

Natural Product ID	NPC471313
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(9Z,12Z)-N-(Pyridin-3-Ylmethyl)Octadeca-9,12-Dienamide
IUPAC Name	(9Z,12Z)-N-(pyridin-3-ylmethyl)octadeca-9,12-dienamide
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2413171
PubChem CID	71770307
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000331] Fatty amides [CHEMONTID:0001096] N-acyl amines

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 65 65 0 0 0 0 0 0 0 0999 V2000 -8.4165 0.4381 -2.0510 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7852 -0.7960 -1.4766 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6252 -0.4913 -0.5587 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5400 0.2588 -1.3032 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3670 0.5681 -0.3793 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8538 1.3956 0.7340 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7888 1.0441 1.9783 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2094 -0.2515 2.4300 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0656 0.0924 3.3148 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8099 -0.2459 3.1108 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3936 -1.0344 1.9321 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3932 -0.2225 1.1199 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8241 0.1199 1.9122 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7688 0.9214 1.0611 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2197 0.1650 -0.1823 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9199 -1.0970 0.1922 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3628 -1.8575 -1.0216 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3466 -1.0796 -1.7899 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8895 -0.0424 -1.2908 N 0 0 0 0 0 0 0 0 0 0 0 0 5.8550 0.8131 -1.9052 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0867 0.8098 -1.0896 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0532 -0.1317 -1.3732 C 0 0 0 0 0 0 0 0 0 0 0 0 9.2160 -0.1920 -0.6593 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4207 0.7023 0.3565 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4790 1.6175 0.6307 N 0 0 0 0 0 0 0 0 0 0 0 0 7.3367 1.6884 -0.0590 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6457 -1.5435 -3.0781 O 0 0 0 0 0 0 0 0 0 0 0 0 -9.5018 0.4508 -1.7474 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.4531 0.3284 -3.1745 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9414 1.3735 -1.7461 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5218 -1.3782 -0.8606 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4563 -1.4948 -2.2996 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2049 -1.4464 -0.2166 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9962 0.0521 0.3132 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9065 1.2175 -1.7085 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1686 -0.3573 -2.1262 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7189 1.2680 -1.0080 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8144 -0.3270 -0.1194 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2973 2.3746 0.4506 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1902 1.7545 2.7404 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0558 -0.6897 3.0859 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0163 -0.9810 1.6742 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2648 0.6897 4.2407 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0357 0.0730 3.8524 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2091 -1.4053 1.3106 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7883 -1.8979 2.3538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0937 -0.8253 0.2340 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8522 0.7210 0.7625 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3179 -0.7673 2.3604 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5485 0.7729 2.7725 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6962 1.1976 1.6073 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2258 1.8244 0.7117 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3754 -0.0016 -0.8924 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9078 0.8468 -0.7022 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3079 -1.7576 0.8485 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8395 -0.8023 0.7838 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4789 -2.1444 -1.6395 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8543 -2.8289 -0.7150 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0367 0.6319 -2.9695 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4429 1.8603 -1.8437 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9082 -0.8590 -2.1850 H 0 0 0 0 0 0 0 0 0 0 0 0 9.9485 -0.9537 -0.9216 H 0 0 0 0 0 0 0 0 0 0 0 0 10.3272 0.6582 0.9159 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5796 2.4363 0.1732 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5154 -1.2630 -3.5036 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 2 0 7 8 1 0 8 9 1 0 9 10 2 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 1 0 17 18 1 0 18 19 2 3 19 20 1 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 18 27 1 0 26 21 1 0 1 28 1 0 1 29 1 0 1 30 1 0 2 31 1 0 2 32 1 0 3 33 1 0 3 34 1 0 4 35 1 0 4 36 1 0 5 37 1 0 5 38 1 0 6 39 1 0 7 40 1 0 8 41 1 0 8 42 1 0 9 43 1 0 10 44 1 0 11 45 1 0 11 46 1 0 12 47 1 0 12 48 1 0 13 49 1 0 13 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 16 55 1 0 16 56 1 0 17 57 1 0 17 58 1 0 20 59 1 0 20 60 1 0 22 61 1 0 23 62 1 0 24 63 1 0 26 64 1 0 27 65 1 0 M END

Standard InCHIKey	MLYVBAFDBYQXMS-HZJYTTRNSA-N
Standard InCHI	InChI=1S/C24H38N2O/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-19-24(27)26-22-23-18-17-20-25-21-23/h6-7,9-10,17-18,20-21H,2-5,8,11-16,19,22H2,1H3,(H,26,27)/b7-6-,10-9-
SMILES	CCCCC/C=CC/C=CCCCCCCCC(=NCc1cccnc1)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	370.3	Volume:	430.069 ? Van der Waals volume.
Dense:	0.861	LogP:	6.389 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.934 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.688 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	9.0
TPSA:	45.48 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.143	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.765	Fsp³:	0.583
MCE-18:	5.0 ? 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:	0.666	Fluc inhibitor:	0.005 ? 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:	0.34 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.296	Promiscuous compounds:	0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.018	MDCK Permeability:	-4.726
Pgp-inhibitor:	0.103	Pgp-substrate:	0.0
PAMPA:	0.001 ? 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%):	0.366	30% Bioavailability (F30%):	0.413
50% Bioavailability (F50%):	0.84

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.008	MRP1:	0.999
Plasma Protein Binding (PPB):	97.439%	Volume Distribution (VD):	-0.026
Fu:	2.528% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.013
OATP1B3 inhibitor:	0.6	BCRP inhibitor:	0.036
BSEP inhibitor:	0.994

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.003	CYP2C19-substrate:	0.471
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.003
CYP2D6-inhibitor:	0.994	CYP2D6-substrate:	0.922
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.994	CYP2C8-inhibitor:	1.0
HLM stability:	0.191 ? 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):

5.416

Half-life (T1/2):

0.299

ADMET: Toxicity

hERG Blockers:	0.265	hERG Blockers (10um):	0.563
Human Hepatotoxicity (H-HT):	0.651	Drug-induced Liver Injury (DILI):	0.013
AMES Toxicity:	0.455	Rat Oral Acute Toxicity:	0.055
Maximum Recommended Daily Dose:	0.214	Skin Sensitization:	1.0
Carcinogencity:	0.27	Eye Corrosion:	0.045
Eye Irritation:	0.971	Respiratory Toxicity:	0.915
Drug-induced Neurotoxicity:	0.039	Ototoxicity:	0.124
Hematotoxicity:	0.008	Drug-induced Nephrotoxicity:	0.794
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.01
A549 Cytotoxicity:	0.035	Hek293 Cytotoxicity:	0.062
BCF:	1.443 ? 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:	4.918 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.088 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.167 ? 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
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12932133]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23891163]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[24972328]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33320645]
NPO18988	Lepidium meyenii	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO18988	Lepidium meyenii	Species	Brassicaceae	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

Activity Type	# Activity
IC50	1
Imax	1
Inhibition	2
Activity	1

Activity Type	# Activity
Individual protein	4
Cell line	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1418	Individual protein	Anandamide amidohydrolase	Homo sapiens	IC50	=	8410.0	nM	PubChem BioAssay data set
NPT1418	Individual protein	Anandamide amidohydrolase	Homo sapiens	Imax	=	94.0	%	PMID[23891163]
NPT1418	Individual protein	Anandamide amidohydrolase	Homo sapiens	Inhibition	=	52.2	%	PMID[25611519]
NPT1418	Individual protein	Anandamide amidohydrolase	Homo sapiens	Inhibition	=	81.9	%	PMID[16499313]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT30043	Cell line	Vero	Chlorocebus sabaeus	Activity	n.a.	n.a.	n.a.	PMID[36655123]

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 NPC471313 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	30730
0.1-0.2	18344
0.2-0.3	713
0.3-0.4	41
0.4-0.5	17
0.5-0.6	10
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9362	High Similarity	NPC471311
0.6296	Remote Similarity	NPC209764
0.6	Remote Similarity	NPC121872
0.5818	Remote Similarity	NPC483616
0.5741	Remote Similarity	NPC74936
0.5741	Remote Similarity	NPC159178
0.5645	Remote Similarity	NPC289330
0.5484	Remote Similarity	NPC483621
0.5397	Remote Similarity	NPC160120
0.5357	Remote Similarity	NPC483617
0.5238	Remote Similarity	NPC483619
0.5238	Remote Similarity	NPC483622
0.5161	Remote Similarity	NPC53596

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC471313 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3543
0.1-0.2	5406
0.2-0.3	187
0.3-0.4	12
0.4-0.5	1
0.5-0.6	0
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
		NPD

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