NPASS Compound

Natural Product: NPC556834

Natural Product ID	NPC556834
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	methyl octadeca-6,9,12-trienoate
IUPAC Name	methyl octadeca-6,9,12-trienoate
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 53 52 0 0 0 0 0 0 0 0999 V2000 -7.6213 -1.7723 -1.1218 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0946 -0.3884 -0.7786 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5015 -0.3243 0.5893 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3416 -1.2548 0.7973 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1964 -0.9883 -0.1411 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6889 0.3934 0.0440 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4418 0.5937 0.4024 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9477 1.9871 0.5840 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8322 2.1637 -0.3740 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3867 2.4541 -0.0247 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8387 2.6498 1.3663 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9068 1.6683 1.7417 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3509 0.7597 0.8915 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4053 -0.1954 1.2899 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5938 -0.0058 0.3780 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2313 -0.2611 -1.0526 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5001 -0.0493 -1.8686 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5239 -1.0039 -1.3928 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3977 -2.2127 -1.6992 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6160 -0.6387 -0.6268 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5942 -1.5661 -0.1747 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8955 -2.5681 -0.8488 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5600 -1.9899 -0.5736 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.8542 -1.7939 -2.2070 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0032 0.2778 -0.7616 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4484 0.0180 -1.5693 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2955 -0.6334 1.3135 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2623 0.7204 0.8219 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9609 -1.0722 1.8287 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6559 -2.3114 0.7557 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3850 -1.6919 0.1302 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4445 -1.2059 -1.1988 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4037 1.1926 -0.1335 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7576 -0.2179 0.5706 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7495 2.7053 0.2513 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7266 2.2228 1.6224 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0377 2.0436 -1.4615 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1373 2.5612 -0.8454 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0772 2.6261 2.1291 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2599 3.7000 1.3942 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3166 1.7187 2.7440 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9438 0.7034 -0.1033 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0185 -1.2408 1.2481 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7175 0.0470 2.3490 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4304 -0.6263 0.7337 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8655 1.0829 0.4610 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4357 0.3909 -1.4071 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9172 -1.3028 -1.2425 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2493 -0.3370 -2.9123 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8388 0.9924 -1.8736 H 0 0 0 0 0 0 0 0 0 0 0 0 9.3167 -1.8328 -0.9719 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1254 -2.4870 0.2350 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1109 -1.0746 0.6924 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 3 7 8 1 0 8 9 1 0 9 10 2 3 10 11 1 0 11 12 1 0 12 13 2 3 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 1 22 1 0 1 23 1 0 1 24 1 0 2 25 1 0 2 26 1 0 3 27 1 0 3 28 1 0 4 29 1 0 4 30 1 0 5 31 1 0 5 32 1 0 6 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 10 38 1 0 11 39 1 0 11 40 1 0 12 41 1 0 13 42 1 0 14 43 1 0 14 44 1 0 15 45 1 0 15 46 1 0 16 47 1 0 16 48 1 0 17 49 1 0 17 50 1 0 21 51 1 0 21 52 1 0 21 53 1 0 M END

Standard InCHIKey	JFRWATCOFCPIBM-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C19H32O2/c1-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19(20)21-2/h7-8,10-11,13-14H,3-6,9,12,15-18H2,1-2H3
SMILES	CCCCCC=CCC=CCC=CCCCCC(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	292.24	Volume:	344.215 ? Van der Waals volume.
Dense:	0.849	LogP:	6.487 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.874 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.761 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	14.0	Rigid Bonds:	4.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.245	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.558	Fsp³:	0.632
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:	0.165	Fluc inhibitor:	0.322 ? 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:	0.013 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.996	Promiscuous compounds:	0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.98	MDCK Permeability:	-4.745
Pgp-inhibitor:	0.519	Pgp-substrate:	0.059
PAMPA:	0.006 ? 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):	0.025
20% Bioavailability (F20%):	0.113	30% Bioavailability (F30%):	0.701
50% Bioavailability (F50%):	0.72

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.302	MRP1:	0.983
Plasma Protein Binding (PPB):	97.988%	Volume Distribution (VD):	-0.43
Fu:	1.627% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.08
OATP1B3 inhibitor:	0.717	BCRP inhibitor:	0.558
BSEP inhibitor:	0.992

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.999
CYP2C19-inhibitor:	0.934	CYP2C19-substrate:	0.173
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	1.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.996 ? 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):

6.255

Half-life (T1/2):

0.21

ADMET: Toxicity

hERG Blockers:	0.26	hERG Blockers (10um):	0.55
Human Hepatotoxicity (H-HT):	0.066	Drug-induced Liver Injury (DILI):	0.001
AMES Toxicity:	0.354	Rat Oral Acute Toxicity:	0.07
Maximum Recommended Daily Dose:	0.074	Skin Sensitization:	1.0
Carcinogencity:	0.207	Eye Corrosion:	0.997
Eye Irritation:	0.997	Respiratory Toxicity:	0.712
Drug-induced Neurotoxicity:	0.029	Ototoxicity:	0.149
Hematotoxicity:	0.013	Drug-induced Nephrotoxicity:	0.232
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.027
A549 Cytotoxicity:	0.056	Hek293 Cytotoxicity:	0.028
BCF:	1.942 ? 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:	4.582 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.85 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.019 ? 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
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	fruit	n.a.	PMID[10606547]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[34771092]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38786901]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	Fruits	n.a.		Database[Phenol-Explorer]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.		Database[Phenol-Explorer]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO25443	Citrus reticulata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO10082	Citrus unshiu	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25443	Citrus reticulata	Species	Rutaceae	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 NPC556834 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	23167
0.1-0.2	24259
0.2-0.3	1998
0.3-0.4	303
0.4-0.5	93
0.5-0.6	17
0.6-0.7	14
0.7-0.8	0
0.8-0.85	1
0.85-0.9	1
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.963	High Similarity	NPC39633
0.8519	High Similarity	NPC309606
0.8276	Intermediate Similarity	NPC139545
0.7333	Intermediate Similarity	NPC228473
0.7188	Intermediate Similarity	NPC28779
0.6296	Remote Similarity	NPC201622
0.6296	Remote Similarity	NPC305660
0.6296	Remote Similarity	NPC161097
0.6296	Remote Similarity	NPC28598
0.6296	Remote Similarity	NPC22903
0.6296	Remote Similarity	NPC54980
0.625	Remote Similarity	NPC128061
0.6216	Remote Similarity	NPC475443
0.6216	Remote Similarity	NPC473829
0.6176	Remote Similarity	NPC10316
0.6176	Remote Similarity	NPC200845
0.6053	Remote Similarity	NPC330426
0.6053	Remote Similarity	NPC127091
0.6053	Remote Similarity	NPC22101
0.5946	Remote Similarity	NPC81896
0.5897	Remote Similarity	NPC54925
0.5789	Remote Similarity	NPC321919
0.5714	Remote Similarity	NPC223677
0.5667	Remote Similarity	NPC216130
0.5556	Remote Similarity	NPC476548
0.5484	Remote Similarity	NPC155880
0.5405	Remote Similarity	NPC277597
0.5405	Remote Similarity	NPC148192
0.5385	Remote Similarity	NPC57499
0.5349	Remote Similarity	NPC473559
0.5349	Remote Similarity	NPC324981
0.5263	Remote Similarity	NPC104537
0.525	Remote Similarity	NPC271921
0.5185	Remote Similarity	NPC219536
0.5185	Remote Similarity	NPC31551
0.5128	Remote Similarity	NPC245002

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC556834 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7032
0.1-0.2	1999
0.2-0.3	93
0.3-0.4	19
0.4-0.5	5
0.5-0.6	2
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
0.5588	Remote Similarity	NPD5343	Phase 4
0.5278	Remote Similarity	NPD6096	Phase 4

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