NPASS Compound

Natural Product: NPC73245

Natural Product ID	NPC73245
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Pentadeca-6,8,10-Triynoic Acid
IUPAC Name	pentadeca-6,8,10-triynoic acid
Synonyms	Pentadeca-6,8,10-Triynoic Acid
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL447088
PubChem CID	10633230
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 35 34 0 0 0 0 0 0 0 0999 V2000 5.3686 0.1941 1.0837 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4369 1.0778 0.5369 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9680 2.4731 0.3914 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9701 2.8649 -0.5652 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6498 2.0594 -0.4601 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7407 1.5024 -0.3819 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5944 0.7874 -0.2845 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5212 0.0964 -0.2021 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6453 -0.6661 -0.0938 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7210 -1.3922 -0.0044 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8826 -2.1955 0.0815 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7905 -1.6779 -1.1436 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1370 -2.2526 -1.0821 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0253 -1.6172 -0.0371 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2846 -0.1820 -0.4153 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6274 0.4721 -1.2194 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.3805 0.4722 0.2072 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5898 0.7561 1.6462 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8387 -0.4844 1.8929 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9413 -0.4670 0.3451 H 0 0 0 0 0 0 0 0 0 0 0 0 7.3183 1.0808 1.2415 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7906 0.6227 -0.4439 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9243 3.1289 0.2705 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6595 2.7837 1.4280 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2950 2.6126 -1.6342 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7125 3.9168 -0.6051 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4503 -2.0032 1.0059 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7476 -3.2513 -0.1872 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7019 -0.5880 -1.0090 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1929 -2.0046 -2.0361 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9818 -3.3579 -0.6538 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5917 -2.4406 -2.0318 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9662 -2.1790 0.0976 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5421 -1.5714 0.9789 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6508 1.4293 -0.0904 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 3 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 2 0 15 17 1 0 1 18 1 0 1 19 1 0 1 20 1 0 2 21 1 0 2 22 1 0 3 23 1 0 3 24 1 0 4 25 1 0 4 26 1 0 11 27 1 0 11 28 1 0 12 29 1 0 12 30 1 0 13 31 1 0 13 32 1 0 14 33 1 0 14 34 1 0 17 35 1 0 M END

Standard InCHIKey	ZRUBGTBVDWZJCR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C15H18O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15(16)17/h2-4,11-14H2,1H3,(H,16,17)
SMILES	CCCCC#CC#CC#CCCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	230.13	Volume:	267.121 ? Van der Waals volume.
Dense:	0.862	LogP:	4.492 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.944 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.764 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	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:	0.562	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.983	Fsp³:	0.533
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:	0.008 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.13 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.157 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.743	Promiscuous compounds:	0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.755	MDCK Permeability:	-4.63
Pgp-inhibitor:	0.01	Pgp-substrate:	0.0
PAMPA:	1.0 ? 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):	0.001
20% Bioavailability (F20%):	0.0	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.963

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.0
Plasma Protein Binding (PPB):	98.186%	Volume Distribution (VD):	0.15
Fu:	0.477% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.0
OATP1B3 inhibitor:	0.004	BCRP inhibitor:	1.0
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.007
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.773	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):

6.4

Half-life (T1/2):

1.308

ADMET: Toxicity

hERG Blockers:	0.048	hERG Blockers (10um):	0.226
Human Hepatotoxicity (H-HT):	0.445	Drug-induced Liver Injury (DILI):	0.414
AMES Toxicity:	0.194	Rat Oral Acute Toxicity:	0.37
Maximum Recommended Daily Dose:	0.607	Skin Sensitization:	0.903
Carcinogencity:	0.395	Eye Corrosion:	0.989
Eye Irritation:	0.994	Respiratory Toxicity:	0.979
Drug-induced Neurotoxicity:	0.104	Ototoxicity:	0.471
Hematotoxicity:	0.16	Drug-induced Nephrotoxicity:	0.277
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.048
A549 Cytotoxicity:	0.007	Hek293 Cytotoxicity:	0.086
BCF:	0.968 ? 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:	3.557 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.797 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.774 ? 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	=	55.0	%	PMID[19805559]
NPT2	Others	Unspecified	n.a.	Inhibition	=	36.0	%	PMID[20591538]
NPT2	Others	Unspecified	n.a.	Inhibition	=	18.0	%	PMID[14640522]

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 NPC73245 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	39842
0.1-0.2	9128
0.2-0.3	642
0.3-0.4	137
0.4-0.5	62
0.5-0.6	33
0.6-0.7	8
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	Natural Product ID
0.7097	Intermediate Similarity	NPC129972
0.7097	Intermediate Similarity	NPC301528
0.7097	Intermediate Similarity	NPC71317
0.7097	Intermediate Similarity	NPC163746
0.7097	Intermediate Similarity	NPC103286
0.6857	Remote Similarity	NPC18357
0.6757	Remote Similarity	NPC28205
0.6562	Remote Similarity	NPC8219
0.6486	Remote Similarity	NPC304162
0.6154	Remote Similarity	NPC274290
0.6071	Remote Similarity	NPC175342
0.6	Remote Similarity	NPC187777
0.6	Remote Similarity	NPC473863
0.5862	Remote Similarity	NPC155263
0.575	Remote Similarity	NPC100096
0.5714	Remote Similarity	NPC158179
0.5714	Remote Similarity	NPC226592
0.5667	Remote Similarity	NPC171736
0.5667	Remote Similarity	NPC301585
0.5667	Remote Similarity	NPC261080
0.5667	Remote Similarity	NPC132565
0.5667	Remote Similarity	NPC209970
0.5667	Remote Similarity	NPC216630
0.5667	Remote Similarity	NPC201844
0.5667	Remote Similarity	NPC301696
0.5667	Remote Similarity	NPC196924
0.5667	Remote Similarity	NPC307783
0.5667	Remote Similarity	NPC154186
0.5667	Remote Similarity	NPC149184
0.5667	Remote Similarity	NPC279026
0.5667	Remote Similarity	NPC113928
0.5667	Remote Similarity	NPC14227
0.5556	Remote Similarity	NPC174368
0.5484	Remote Similarity	NPC604140
0.5476	Remote Similarity	NPC54766
0.5385	Remote Similarity	NPC284212
0.5357	Remote Similarity	NPC134782
0.5357	Remote Similarity	NPC268826
0.5278	Remote Similarity	NPC19305
0.5278	Remote Similarity	NPC602547
0.5227	Remote Similarity	NPC470410
0.5227	Remote Similarity	NPC470412
0.5172	Remote Similarity	NPC214610
0.5172	Remote Similarity	NPC118968
0.5172	Remote Similarity	NPC183424
0.5172	Remote Similarity	NPC294085

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC73245 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6824
0.1-0.2	2099
0.2-0.3	187
0.3-0.4	28
0.4-0.5	8
0.5-0.6	4
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
0.5667	Remote Similarity	NPD2270	Pre-clinical
0.5667	Remote Similarity	NPD633	Phase 3
0.5667	Remote Similarity	NPD9448	Phase 2
0.5172	Remote Similarity	NPD9655	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