NPASS Compound

Natural Product: NPC509785

Natural Product ID	NPC509785
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	henicosa-4,7-dienoic acid
IUPAC Name	henicosa-4,7-dienoic 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 61 60 0 0 0 0 0 0 0 0999 V2000 -7.5411 -1.5005 0.2799 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8324 -0.4471 -0.5068 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5506 -0.9648 -1.1154 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6179 -1.4484 -0.0399 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2394 -0.3807 0.9481 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3065 -0.8336 2.0089 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0171 -1.4307 1.7060 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0321 -0.6228 0.9493 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4207 -0.3095 -0.4475 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2881 0.4694 -1.1253 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0304 1.7483 -0.4027 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0536 2.5416 -1.1413 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3146 1.7096 -1.1708 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4046 2.4344 -1.8647 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5205 2.7556 -1.3190 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8820 2.4518 0.0809 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0826 1.5905 0.1177 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0950 0.4114 0.6493 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9473 -0.2286 1.2787 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5619 -1.5337 0.5904 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6822 -2.4810 0.6911 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6913 -3.5636 0.0385 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7562 -2.2041 1.5107 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.6340 -1.2900 0.2486 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4145 -2.5269 -0.0957 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2654 -1.4714 1.3629 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5281 -0.1149 -1.3127 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5810 0.3958 0.1742 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7761 -1.8726 -1.7482 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0859 -0.1961 -1.7679 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1817 -2.2298 0.5560 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7515 -2.0023 -0.4461 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2334 -0.1712 1.5746 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0909 0.6202 0.5386 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8896 -1.5562 2.7008 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1533 0.0496 2.7393 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2232 -2.3982 1.1073 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4767 -1.7954 2.6473 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0010 -1.0879 0.9827 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8701 0.3777 1.4696 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4980 -1.3000 -1.0114 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3320 0.2607 -0.5354 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5453 0.6912 -2.1695 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5957 -0.2259 -1.0469 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3819 1.5711 0.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9453 2.3602 -0.2852 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2318 3.5203 -0.6660 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6528 2.7296 -2.1553 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5175 1.3824 -0.1551 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1495 0.7641 -1.7583 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2509 2.7208 -2.9285 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2886 3.2931 -1.8924 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0478 2.1435 0.7029 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2665 3.4550 0.5267 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9825 2.0369 -0.3514 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0412 -0.1396 0.6209 H 0 0 0 0 0 0 0 0 0 0 0 0 5.3068 -0.5415 2.3219 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0729 0.3856 1.4892 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2216 -1.3473 -0.4502 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6991 -2.0007 1.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6540 -2.6538 1.4435 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 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 3 15 16 1 0 16 17 1 0 17 18 2 3 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 1 24 1 0 1 25 1 0 1 26 1 0 2 27 1 0 2 28 1 0 3 29 1 0 3 30 1 0 4 31 1 0 4 32 1 0 5 33 1 0 5 34 1 0 6 35 1 0 6 36 1 0 7 37 1 0 7 38 1 0 8 39 1 0 8 40 1 0 9 41 1 0 9 42 1 0 10 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 15 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 18 56 1 0 19 57 1 0 19 58 1 0 20 59 1 0 20 60 1 0 23 61 1 0 M END

Standard InCHIKey	HXJAKZFPMQDMKS-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C21H38O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21(22)23/h14-15,17-18H,2-13,16,19-20H2,1H3,(H,22,23)
SMILES	CCCCCCCCCCCCCC=CCC=CCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	322.29	Volume:	381.443 ? Van der Waals volume.
Dense:	0.845	LogP:	8.09 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.066 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.651 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	17.0	Rigid Bonds:	3.0
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:	0.23	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.335	Fsp³:	0.762
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:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.529	Fluc inhibitor:	0.315 ? 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:	0.016 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.993	Promiscuous compounds:	0.906

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.039	MDCK Permeability:	-4.726
Pgp-inhibitor:	0.0	Pgp-substrate:	0.003
PAMPA:	0.012 ? 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):	0.31
20% Bioavailability (F20%):	0.372	30% Bioavailability (F30%):	0.844
50% Bioavailability (F50%):	0.432

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.018	MRP1:	0.987
Plasma Protein Binding (PPB):	98.467%	Volume Distribution (VD):	0.579
Fu:	0.882% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.432
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.176
BSEP inhibitor:	0.299

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.077
CYP2C19-inhibitor:	0.004	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.047
CYP2D6-inhibitor:	0.979	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.998	CYP2C8-inhibitor:	0.994
HLM stability:	0.001 ? 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):

4.519

Half-life (T1/2):

0.578

ADMET: Toxicity

hERG Blockers:	0.12	hERG Blockers (10um):	0.376
Human Hepatotoxicity (H-HT):	0.144	Drug-induced Liver Injury (DILI):	0.019
AMES Toxicity:	0.065	Rat Oral Acute Toxicity:	0.108
Maximum Recommended Daily Dose:	0.05	Skin Sensitization:	0.999
Carcinogencity:	0.102	Eye Corrosion:	0.999
Eye Irritation:	0.999	Respiratory Toxicity:	0.877
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.156
Hematotoxicity:	0.043	Drug-induced Nephrotoxicity:	0.216
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.023
A549 Cytotoxicity:	0.157	Hek293 Cytotoxicity:	0.026
BCF:	0.737 ? 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:	4.04 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.672 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.959 ? 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
NPO63497	Bathysiphon lanosum	Genus	Bathysiphonidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC509785 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	37940
0.1-0.2	10268
0.2-0.3	1264
0.3-0.4	239
0.4-0.5	97
0.5-0.6	18
0.6-0.7	21
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
0.7576	Intermediate Similarity	NPC154245
0.7576	Intermediate Similarity	NPC85813
0.7576	Intermediate Similarity	NPC223697
0.7576	Intermediate Similarity	NPC59051
0.7576	Intermediate Similarity	NPC6095
0.7273	Intermediate Similarity	NPC321062
0.7273	Intermediate Similarity	NPC91495
0.7273	Intermediate Similarity	NPC5413
0.6774	Remote Similarity	NPC270796
0.6667	Remote Similarity	NPC424
0.6667	Remote Similarity	NPC36061
0.6667	Remote Similarity	NPC69510
0.6667	Remote Similarity	NPC77272
0.6667	Remote Similarity	NPC290563
0.6667	Remote Similarity	NPC139029
0.6667	Remote Similarity	NPC281972
0.6667	Remote Similarity	NPC92114
0.6667	Remote Similarity	NPC261831
0.6667	Remote Similarity	NPC87564
0.6571	Remote Similarity	NPC52955
0.6571	Remote Similarity	NPC88966
0.6571	Remote Similarity	NPC25417
0.6571	Remote Similarity	NPC1813
0.6364	Remote Similarity	NPC281245
0.6286	Remote Similarity	NPC70387
0.6	Remote Similarity	NPC149821
0.6	Remote Similarity	NPC95145
0.6	Remote Similarity	NPC325642
0.6	Remote Similarity	NPC65174
0.5714	Remote Similarity	NPC323597
0.5714	Remote Similarity	NPC211752
0.5714	Remote Similarity	NPC323498
0.5581	Remote Similarity	NPC317583
0.5556	Remote Similarity	NPC207292
0.55	Remote Similarity	NPC52264
0.5455	Remote Similarity	NPC320642
0.5455	Remote Similarity	NPC329550
0.5429	Remote Similarity	NPC117572
0.5405	Remote Similarity	NPC224227
0.5333	Remote Similarity	NPC323045
0.5333	Remote Similarity	NPC317881
0.525	Remote Similarity	NPC137538
0.5238	Remote Similarity	NPC477201
0.5217	Remote Similarity	NPC322461
0.5122	Remote Similarity	NPC487561
0.5106	Remote Similarity	NPC605544
0.5106	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 NPC509785 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6805
0.1-0.2	2115
0.2-0.3	185
0.3-0.4	24
0.4-0.5	10
0.5-0.6	3
0.6-0.7	4
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
0.7632	Intermediate Similarity	NPD39	Phase 4
0.7576	Intermediate Similarity	NPD4266	Phase 2
0.7273	Intermediate Similarity	NPD3173	Phase 4
0.6774	Remote Similarity	NPD5326	Phase 3
0.6667	Remote Similarity	NPD3195	Phase 2
0.6667	Remote Similarity	NPD3196	Approved
0.6571	Remote Similarity	NPD3172	Approved
0.55	Remote Similarity	NPD3194	Phase 4
0.5429	Remote Similarity	NPD4222	Phase 3
0.5135	Remote Similarity	NPD3174	Discontinued

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