NPASS Compound

Natural Product: NPC503962

Natural Product ID	NPC503962
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	13-methoxy-heneicosanoic acid
IUPAC Name	13-methoxyhenicosanoic 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

Standard InCHIKey	MZXNTCGVKVBBBA-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C22H44O3/c1-3-4-5-6-12-15-18-21(25-2)19-16-13-10-8-7-9-11-14-17-20-22(23)24/h21H,3-20H2,1-2H3,(H,23,24)
SMILES	CCCCCCCCC(CCCCCCCCCCCC(=O)O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	356.33	Volume:	412.802 ? Van der Waals volume.
Dense:	0.863	LogP:	7.098 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.947 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.402 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	20.0	Rigid Bonds:	1.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.236	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.575	Fsp³:	0.955
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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.189	Fluc inhibitor:	0.206 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.003 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.006 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.98	Promiscuous compounds:	0.196

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.196	MDCK Permeability:	-4.801
Pgp-inhibitor:	0.0	Pgp-substrate:	0.017
PAMPA:	0.027 ? 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):	0.914
20% Bioavailability (F20%):	0.799	30% Bioavailability (F30%):	0.961
50% Bioavailability (F50%):	0.511

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.009	MRP1:	0.996
Plasma Protein Binding (PPB):	97.599%	Volume Distribution (VD):	0.637
Fu:	2.223% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.188
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.247
BSEP inhibitor:	0.142

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.919
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.012
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.921
CYP2D6-inhibitor:	0.998	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.998	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):

4.004

Half-life (T1/2):

1.005

ADMET: Toxicity

hERG Blockers:	0.119	hERG Blockers (10um):	0.26
Human Hepatotoxicity (H-HT):	0.601	Drug-induced Liver Injury (DILI):	0.2
AMES Toxicity:	0.008	Rat Oral Acute Toxicity:	0.019
Maximum Recommended Daily Dose:	0.094	Skin Sensitization:	0.987
Carcinogencity:	0.382	Eye Corrosion:	0.987
Eye Irritation:	0.997	Respiratory Toxicity:	0.879
Drug-induced Neurotoxicity:	0.007	Ototoxicity:	0.653
Hematotoxicity:	0.218	Drug-induced Nephrotoxicity:	0.729
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.026
A549 Cytotoxicity:	0.018	Hek293 Cytotoxicity:	0.014
BCF:	0.621 ? 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:	4.01 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.769 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.755 ? 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
NPO2061	Schizymenia dubyi	Species	Schizymeniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2061	Schizymenia dubyi	Species	Schizymeniaceae	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 NPC503962 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	32973
0.1-0.2	15238
0.2-0.3	1339
0.3-0.4	168
0.4-0.5	73
0.5-0.6	42
0.6-0.7	7
0.7-0.8	3
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7143	Intermediate Similarity	NPC171736
0.7143	Intermediate Similarity	NPC301585
0.7143	Intermediate Similarity	NPC261080
0.7143	Intermediate Similarity	NPC132565
0.7143	Intermediate Similarity	NPC209970
0.7143	Intermediate Similarity	NPC216630
0.7143	Intermediate Similarity	NPC201844
0.7143	Intermediate Similarity	NPC301696
0.7143	Intermediate Similarity	NPC196924
0.7143	Intermediate Similarity	NPC307783
0.7143	Intermediate Similarity	NPC154186
0.7143	Intermediate Similarity	NPC149184
0.7143	Intermediate Similarity	NPC279026
0.7143	Intermediate Similarity	NPC113928
0.7143	Intermediate Similarity	NPC14227
0.697	Remote Similarity	NPC602547
0.6786	Remote Similarity	NPC155263
0.6071	Remote Similarity	NPC214610
0.6071	Remote Similarity	NPC118968
0.6071	Remote Similarity	NPC183424
0.6071	Remote Similarity	NPC294085
0.6053	Remote Similarity	NPC52264
0.5882	Remote Similarity	NPC424
0.5882	Remote Similarity	NPC36061
0.5882	Remote Similarity	NPC69510
0.5882	Remote Similarity	NPC77272
0.5882	Remote Similarity	NPC8219
0.5882	Remote Similarity	NPC290563
0.5882	Remote Similarity	NPC139029
0.5882	Remote Similarity	NPC281972
0.5882	Remote Similarity	NPC261831
0.5882	Remote Similarity	NPC87564
0.5862	Remote Similarity	NPC175342
0.5789	Remote Similarity	NPC137538
0.5714	Remote Similarity	NPC18712
0.5714	Remote Similarity	NPC74845
0.5714	Remote Similarity	NPC95145
0.5714	Remote Similarity	NPC268826
0.5714	Remote Similarity	NPC325642
0.5714	Remote Similarity	NPC65174
0.5588	Remote Similarity	NPC281245
0.5556	Remote Similarity	NPC87394
0.5556	Remote Similarity	NPC324004
0.5556	Remote Similarity	NPC328497
0.5455	Remote Similarity	NPC55023
0.5455	Remote Similarity	NPC21844
0.5429	Remote Similarity	NPC129972
0.5429	Remote Similarity	NPC301528
0.5429	Remote Similarity	NPC71317
0.5429	Remote Similarity	NPC92114
0.5429	Remote Similarity	NPC163746
0.5429	Remote Similarity	NPC103286
0.5405	Remote Similarity	NPC154245
0.5405	Remote Similarity	NPC85813
0.5405	Remote Similarity	NPC223697
0.5405	Remote Similarity	NPC6095
0.5357	Remote Similarity	NPC174368
0.5349	Remote Similarity	NPC68343
0.5349	Remote Similarity	NPC328089
0.5312	Remote Similarity	NPC604140
0.5172	Remote Similarity	NPC134782
0.5143	Remote Similarity	NPC314679
0.5135	Remote Similarity	NPC321062
0.5128	Remote Similarity	NPC40082

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC503962 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5976
0.1-0.2	2859
0.2-0.3	254
0.3-0.4	43
0.4-0.5	9
0.5-0.6	3
0.6-0.7	2
0.7-0.8	3
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
0.7143	Intermediate Similarity	NPD2270	Pre-clinical
0.7143	Intermediate Similarity	NPD633	Phase 3
0.7143	Intermediate Similarity	NPD9448	Phase 2
0.6071	Remote Similarity	NPD9655	Phase 4
0.6	Remote Similarity	NPD3199	Clinical (unspecified phase)
0.5882	Remote Similarity	NPD3195	Phase 2
0.5882	Remote Similarity	NPD3196	Approved
0.5405	Remote Similarity	NPD4266	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