NPASS Compound

Natural Product: NPC474642

Natural Product ID	NPC474642
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(R,4E,15E)-Docosa-4,15-Dien-1-Yn-3-Ol
IUPAC Name	(3R,4E,15E)-docosa-4,15-dien-1-yn-3-ol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL477904
PubChem CID	10403623
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0001334] Fatty alcohols [CHEMONTID:0002951] Long-chain fatty alcohols

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 7.7287 1.1356 -2.7342 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2946 0.7604 -2.1405 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5390 0.7596 -0.6881 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5403 0.3971 0.3372 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0817 -1.0311 0.3104 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4774 -1.7013 -0.8349 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1612 -1.0879 -1.3315 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7479 -0.1260 -0.5238 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5839 0.7601 -0.5953 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7641 0.4530 -1.8523 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3221 1.5669 -1.8662 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9813 1.5799 -0.4960 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5871 0.3334 -0.1019 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9348 0.0375 1.2452 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8548 0.6006 2.1910 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3031 0.4812 1.7548 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5831 -1.0138 1.5416 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0024 -1.1345 1.1793 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8807 -1.8767 1.6748 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.3769 -1.7060 1.0191 C 0 0 2 0 0 0 0 0 0 0 0 0 -8.6272 -0.4555 1.4443 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.8522 0.6548 1.8392 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.0888 -2.6980 1.5260 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6058 1.8959 -3.4609 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2933 1.5289 -1.8180 H 0 0 0 0 0 0 0 0 0 0 0 0 8.2543 0.2046 -2.9696 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6649 1.6221 -2.4722 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9884 -0.1360 -2.6402 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4940 0.1192 -0.5005 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9625 1.7953 -0.4383 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8349 1.1776 0.6109 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1986 0.4119 1.3367 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0922 -1.6393 0.5136 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5624 -1.2732 1.2899 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1971 -2.7679 -0.5470 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1272 -1.8057 -1.7160 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6226 -1.5262 -2.1685 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2290 -0.1293 0.4746 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9302 1.8285 -0.6116 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9231 0.5804 0.2998 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3214 -0.5009 -1.6558 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3583 0.4293 -2.7627 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3420 2.5260 -1.8045 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8170 1.6069 -2.7689 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6570 2.4865 -0.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1957 1.8856 0.2669 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5496 0.2487 -0.8132 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0414 -0.5945 -0.5811 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1890 -1.1842 1.3009 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9401 -0.1354 1.8502 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7570 -0.0343 3.1492 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5661 1.6056 2.5101 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9547 0.9608 2.4525 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4925 0.8977 0.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2052 -1.6021 2.3539 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0229 -1.3463 0.6105 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3298 -0.4212 0.3263 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8576 -2.6040 2.4908 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.1562 -1.7235 -0.1103 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.1042 1.8940 2.3050 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6906 -2.9710 2.4447 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 2 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 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 1 0 21 22 3 0 20 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 8 38 1 0 9 39 1 0 9 40 1 0 10 41 1 0 10 42 1 0 11 43 1 0 11 44 1 0 12 45 1 0 12 46 1 0 13 47 1 0 13 48 1 0 14 49 1 0 14 50 1 0 15 51 1 0 15 52 1 0 16 53 1 0 16 54 1 0 17 55 1 0 17 56 1 0 18 57 1 0 19 58 1 0 20 59 1 6 22 60 1 0 23 61 1 0 M END

Standard InCHIKey	HEXQBSKJVUFXNG-AMPPGYCNSA-N
Standard InCHI	InChI=1S/C22H38O/c1-3-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22(23)4-2/h2,9-10,20-23H,3,5-8,11-19H2,1H3/b10-9+,21-20+/t22-/m0/s1
SMILES	CCCCCC/C=C/CCCCCCCCC/C=C/[C@H](C#C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	318.29	Volume:	387.313 ? Van der Waals volume.
Dense:	0.822	LogP:	6.959 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	4.263 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.376 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	16.0	Rigid Bonds:	3.0
TPSA:	20.23 ? Topological Polar Surface Area.	H-Bond Acceptor:	1.0
H-Bond Donor:	1.0	Rings:	0.0
Heavy Atoms:	1.0

MedChem Properties

QED Drug-Likeness Score:	0.194	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.128	Fsp³:	0.727
MCE-18:	1.0 ? 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:	0.598	Fluc inhibitor:	0.003 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.002 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.987	Promiscuous compounds:	0.106

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.016	MDCK Permeability:	-4.643
Pgp-inhibitor:	0.019	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):	0.104
20% Bioavailability (F20%):	0.477	30% Bioavailability (F30%):	0.987
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.0
Plasma Protein Binding (PPB):	99.728%	Volume Distribution (VD):	-0.174
Fu:	0.116% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.139
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.922
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.996
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.245
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.906
CYP2D6-inhibitor:	0.811	CYP2D6-substrate:	0.997
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.147 ? 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):

4.787

Half-life (T1/2):

0.644

ADMET: Toxicity

hERG Blockers:	0.086	hERG Blockers (10um):	0.728
Human Hepatotoxicity (H-HT):	0.79	Drug-induced Liver Injury (DILI):	0.018
AMES Toxicity:	0.022	Rat Oral Acute Toxicity:	0.15
Maximum Recommended Daily Dose:	0.587	Skin Sensitization:	0.998
Carcinogencity:	0.221	Eye Corrosion:	0.037
Eye Irritation:	0.899	Respiratory Toxicity:	1.0
Drug-induced Neurotoxicity:	0.143	Ototoxicity:	0.611
Hematotoxicity:	0.019	Drug-induced Nephrotoxicity:	0.39
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.291
A549 Cytotoxicity:	0.854	Hek293 Cytotoxicity:	0.543
BCF:	1.047 ? 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:	5.061 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.68 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.345 ? 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
NPO15047	Cribrochalina vasculum	Species	Niphatidae	Eukaryota	n.a.	Caribbean	n.a.	PMID[1431945]
NPO15047	Cribrochalina vasculum	Species	Niphatidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8691203]
NPO15047	Cribrochalina vasculum	Species	Niphatidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8984159]
NPO15047	Cribrochalina vasculum	Species	Niphatidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15047	Cribrochalina vasculum	Species	Niphatidae	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
-	Artemia salina	LC50	=	0.4	ug.mL-1	PMID[17485499]

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 NPC474642 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	34914
0.1-0.2	13452
0.2-0.3	1079
0.3-0.4	284
0.4-0.5	66
0.5-0.6	23
0.6-0.7	12
0.7-0.8	0
0.8-0.85	5
0.85-0.9	8
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473913
0.9583	High Similarity	NPC249670
0.875	High Similarity	NPC170776
0.875	High Similarity	NPC9273
0.875	High Similarity	NPC165447
0.875	High Similarity	NPC471959
0.875	High Similarity	NPC199286
0.875	High Similarity	NPC489046
0.875	High Similarity	NPC76198
0.875	High Similarity	NPC610719
0.84	Intermediate Similarity	NPC607242
0.8333	Intermediate Similarity	NPC125122
0.8333	Intermediate Similarity	NPC471276
0.8333	Intermediate Similarity	NPC471280
0.8333	Intermediate Similarity	NPC471281
0.7667	Intermediate Similarity	NPC473865
0.7241	Intermediate Similarity	NPC474644
0.7097	Intermediate Similarity	NPC474643
0.6562	Remote Similarity	NPC161838
0.6364	Remote Similarity	NPC471960
0.6364	Remote Similarity	NPC477727
0.6333	Remote Similarity	NPC600749
0.6333	Remote Similarity	NPC601019
0.625	Remote Similarity	NPC91226
0.625	Remote Similarity	NPC243546
0.625	Remote Similarity	NPC31194
0.625	Remote Similarity	NPC248884
0.6061	Remote Similarity	NPC471239
0.6061	Remote Similarity	NPC72699
0.6061	Remote Similarity	NPC55383
0.5946	Remote Similarity	NPC470966
0.5833	Remote Similarity	NPC197272
0.5789	Remote Similarity	NPC477661
0.5789	Remote Similarity	NPC603233
0.5789	Remote Similarity	NPC607245
0.5676	Remote Similarity	NPC89824
0.5676	Remote Similarity	NPC475477
0.5676	Remote Similarity	NPC256656
0.5676	Remote Similarity	NPC294278
0.5676	Remote Similarity	NPC477723
0.5556	Remote Similarity	NPC484320
0.5526	Remote Similarity	NPC471278
0.5417	Remote Similarity	NPC151719
0.5385	Remote Similarity	NPC48058
0.5385	Remote Similarity	NPC470963
0.5357	Remote Similarity	NPC182392
0.5263	Remote Similarity	NPC85079
0.5263	Remote Similarity	NPC151782
0.525	Remote Similarity	NPC470970
0.5172	Remote Similarity	NPC76976
0.5122	Remote Similarity	NPC224148
0.5122	Remote Similarity	NPC477726
0.5122	Remote Similarity	NPC477725

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC474642 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8058
0.1-0.2	1022
0.2-0.3	53
0.3-0.4	15
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