NPASS Compound

Natural Product: NPC274290

Natural Product ID	NPC274290
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(Z)-Hexadec-11-En-7,9-Diynoic Acid
IUPAC Name	(Z)-hexadec-11-en-7,9-diynoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL510276
PubChem CID	10422039
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000262] Fatty acids and conjugates [CHEMONTID:0002949] Long-chain fatty acids

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 40 39 0 0 0 0 0 0 0 0999 V2000 7.0540 -1.8666 -0.2843 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4879 -0.5255 0.0220 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2313 -0.0622 -0.3263 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0328 -0.7236 0.5276 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2638 -2.1846 0.2163 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1489 -3.0589 -0.4675 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2222 -2.2716 -0.5323 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1311 -1.3342 -0.5854 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1914 -0.2321 -0.6334 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9114 0.3641 -0.6650 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2056 1.4527 -0.6974 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3056 0.2637 -0.3820 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6781 0.7379 -0.1997 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9794 1.0749 1.2695 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3609 1.4723 1.2989 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6711 2.6188 0.3797 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6502 3.2748 -0.1184 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8857 3.0529 -0.0219 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0302 -1.6720 -0.8657 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3468 -2.3721 0.6885 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4749 -2.4935 -0.9517 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5686 -0.3368 1.2403 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3197 0.2716 -0.2822 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8963 -0.1325 -1.3474 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1613 1.0770 -0.1100 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2068 -0.2763 0.0565 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1866 -0.3776 1.5407 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0554 -2.6522 0.6408 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3793 -3.8801 -0.7619 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0997 1.6367 0.4901 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0914 1.9617 -1.3811 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2539 -0.4817 -1.1482 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0887 -0.3650 0.6033 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6806 1.7729 -0.7526 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4713 0.0740 -0.6103 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2103 1.4961 1.8752 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0856 -0.1215 1.7108 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0514 0.6012 0.9700 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7996 1.6711 2.3536 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.5262 2.5462 -0.7836 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 2 0 6 7 1 0 7 8 3 0 8 9 1 0 9 10 3 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 2 0 16 18 1 0 1 19 1 0 1 20 1 0 1 21 1 0 2 22 1 0 2 23 1 0 3 24 1 0 3 25 1 0 4 26 1 0 4 27 1 0 5 28 1 0 6 29 1 0 11 30 1 0 11 31 1 0 12 32 1 0 12 33 1 0 13 34 1 0 13 35 1 0 14 36 1 0 14 37 1 0 15 38 1 0 15 39 1 0 18 40 1 0 M END

Standard InCHIKey	ZYKRBUYXWXJLBD-WAYWQWQTSA-N
Standard InCHI	InChI=1S/C16H22O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15-16(17)18/h5-6H,2-4,11-15H2,1H3,(H,17,18)/b6-5-
SMILES	CCCC/C=CC#CC#CCCCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	246.16	Volume:	287.054 ? Van der Waals volume.
Dense:	0.858	LogP:	5.312 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.196 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.39 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	4.0
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:	0.523	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.912	Fsp³:	0.562
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:	0.002	Fluc inhibitor:	0.004 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.009 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.085 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.949	Promiscuous compounds:	0.058

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.927	MDCK Permeability:	-4.833
Pgp-inhibitor:	0.013	Pgp-substrate:	0.0
PAMPA:	0.996 ? 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):	0.003
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.906

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.506
Plasma Protein Binding (PPB):	99.109%	Volume Distribution (VD):	-0.219
Fu:	0.321% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.002	BCRP inhibitor:	0.032
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.753
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.54	CYP2D6-substrate:	0.018
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.006
CYP2B6-substrate:	0.986	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):

3.774

Half-life (T1/2):

1.042

ADMET: Toxicity

hERG Blockers:	0.051	hERG Blockers (10um):	0.264
Human Hepatotoxicity (H-HT):	0.345	Drug-induced Liver Injury (DILI):	0.195
AMES Toxicity:	0.12	Rat Oral Acute Toxicity:	0.195
Maximum Recommended Daily Dose:	0.583	Skin Sensitization:	0.969
Carcinogencity:	0.282	Eye Corrosion:	0.997
Eye Irritation:	0.995	Respiratory Toxicity:	0.985
Drug-induced Neurotoxicity:	0.053	Ototoxicity:	0.466
Hematotoxicity:	0.061	Drug-induced Nephrotoxicity:	0.204
Genotoxicity:	0.0	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.012	Hek293 Cytotoxicity:	0.133
BCF:	1.157 ? 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:	3.806 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.097 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.49 ? 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
NPO32503	heisteria acuminata	Species	Erythropalaceae	Eukaryota	bark	n.a.	n.a.	PMID[9584394]
NPO32503	heisteria acuminata	Species	Erythropalaceae	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

Activity Type	# Activity
Inhibition	3

Activity Type	# Activity
Others	3

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
NPT2	Others	Unspecified	n.a.	Inhibition	=	51.0	%	Open TG-GATES in vivo data: Biochemistry
NPT2	Others	Unspecified	n.a.	Inhibition	=	36.0	%	PMID[21861991]
NPT2	Others	Unspecified	n.a.	Inhibition	=	45.0	%	PMID[15620246]

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 NPC274290 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	36700
0.1-0.2	12168
0.2-0.3	721
0.3-0.4	130
0.4-0.5	89
0.5-0.6	34
0.6-0.7	9
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	1
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.973	High Similarity	NPC187777
0.9189	High Similarity	NPC28205
0.8049	Intermediate Similarity	NPC54766
0.7561	Intermediate Similarity	NPC179764
0.6977	Remote Similarity	NPC473863
0.6809	Remote Similarity	NPC225066
0.6667	Remote Similarity	NPC129458
0.6667	Remote Similarity	NPC226592
0.6383	Remote Similarity	NPC45626
0.6304	Remote Similarity	NPC267817
0.619	Remote Similarity	NPC18357
0.6154	Remote Similarity	NPC73245
0.6047	Remote Similarity	NPC225929
0.5957	Remote Similarity	NPC303765
0.5897	Remote Similarity	NPC8219
0.5833	Remote Similarity	NPC470410
0.5833	Remote Similarity	NPC470412
0.5641	Remote Similarity	NPC281245
0.5556	Remote Similarity	NPC304162
0.55	Remote Similarity	NPC129972
0.55	Remote Similarity	NPC424
0.55	Remote Similarity	NPC36061
0.55	Remote Similarity	NPC69510
0.55	Remote Similarity	NPC77272
0.55	Remote Similarity	NPC301528
0.55	Remote Similarity	NPC290563
0.55	Remote Similarity	NPC139029
0.55	Remote Similarity	NPC281972
0.55	Remote Similarity	NPC71317
0.55	Remote Similarity	NPC261831
0.55	Remote Similarity	NPC87564
0.55	Remote Similarity	NPC163746
0.55	Remote Similarity	NPC103286
0.5366	Remote Similarity	NPC196831
0.5366	Remote Similarity	NPC95145
0.5366	Remote Similarity	NPC325642
0.5366	Remote Similarity	NPC65174
0.5306	Remote Similarity	NPC470320
0.5306	Remote Similarity	NPC235242
0.5238	Remote Similarity	NPC321062
0.5122	Remote Similarity	NPC92114
0.5116	Remote Similarity	NPC154245
0.5116	Remote Similarity	NPC85813
0.5116	Remote Similarity	NPC223697
0.5116	Remote Similarity	NPC6095
0.5102	Remote Similarity	NPC10081
0.5098	Remote Similarity	NPC329819

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC274290 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6672
0.1-0.2	2315
0.2-0.3	132
0.3-0.4	18
0.4-0.5	10
0.5-0.6	3
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
0.55	Remote Similarity	NPD3195	Phase 2
0.55	Remote Similarity	NPD3196	Approved
0.5116	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