NPASS Compound

Natural Product: NPC28205

Natural Product ID	NPC28205
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(E)-Pentadec-10-En-6,8-Diynoic Acid
IUPAC Name	(E)-pentadec-10-en-6,8-diynoic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL448670
PubChem CID	10443953
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 37 36 0 0 0 0 0 0 0 0999 V2000 -6.8517 1.4182 1.2233 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8912 0.7551 0.2799 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5399 -0.5812 0.9025 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6734 -1.4071 0.0514 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3221 -0.8068 -0.3192 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2089 -1.6165 0.0490 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0096 -1.0649 -0.2907 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0433 -0.5764 -0.5689 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3760 0.0693 -0.9335 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2959 0.5114 -1.1663 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7020 1.1652 -1.4997 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6758 -0.0181 -1.5793 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8899 -0.8088 -0.3651 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4385 -0.0884 0.8228 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6924 0.5841 0.5491 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3532 0.6650 -0.4784 O 0 0 0 0 0 0 0 0 0 0 0 0 7.3023 1.2687 1.6774 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.8873 1.1935 0.8328 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7868 0.9563 2.2150 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6781 2.5330 1.2756 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9499 1.3194 0.1042 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3921 0.5706 -0.7019 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0232 -0.3726 1.8289 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5072 -1.1077 1.0315 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0974 -1.5928 -1.0304 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5136 -2.3948 0.4730 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2462 0.1371 -0.8129 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5006 -2.5498 0.4927 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6290 1.5651 -2.5056 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9346 1.8114 -0.7227 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6342 0.3814 -1.9729 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3060 -0.6992 -2.3885 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7548 -1.5814 -0.6045 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0598 -1.5370 -0.1305 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7181 -0.8938 1.6211 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6494 0.5552 1.2747 H 0 0 0 0 0 0 0 0 0 0 0 0 7.6239 2.2370 1.4581 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 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 5 27 1 0 6 28 1 0 11 29 1 0 11 30 1 0 12 31 1 0 12 32 1 0 13 33 1 0 13 34 1 0 14 35 1 0 14 36 1 0 17 37 1 0 M END

Standard InCHIKey	VLPCQMHZJMTSIW-AATRIKPKSA-N
Standard InCHI	InChI=1S/C15H20O2/c1-2-3-4-5-6-7-8-9-10-11-12-13-14-15(16)17/h5-6H,2-4,11-14H2,1H3,(H,16,17)/b6-5+
SMILES	CCCC/C=C/C#CC#CCCCCC(=O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	232.15	Volume:	269.758 ? Van der Waals volume.
Dense:	0.861	LogP:	4.637 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.041 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.889 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	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:	0.539	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.961	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:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.01 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.095 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.964	Promiscuous compounds:	0.049

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.829	MDCK Permeability:	-4.82
Pgp-inhibitor:	0.003	Pgp-substrate:	0.001
PAMPA:	0.995 ? 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):	0.004
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.499

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.037
Plasma Protein Binding (PPB):	99.078%	Volume Distribution (VD):	-0.346
Fu:	0.363% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.01
OATP1B3 inhibitor:	0.07	BCRP inhibitor:	0.159
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.048
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.312	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.612	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):

6.466

Half-life (T1/2):

1.02

ADMET: Toxicity

hERG Blockers:	0.06	hERG Blockers (10um):	0.205
Human Hepatotoxicity (H-HT):	0.5	Drug-induced Liver Injury (DILI):	0.472
AMES Toxicity:	0.196	Rat Oral Acute Toxicity:	0.204
Maximum Recommended Daily Dose:	0.394	Skin Sensitization:	0.688
Carcinogencity:	0.267	Eye Corrosion:	0.964
Eye Irritation:	0.994	Respiratory Toxicity:	0.967
Drug-induced Neurotoxicity:	0.148	Ototoxicity:	0.489
Hematotoxicity:	0.206	Drug-induced Nephrotoxicity:	0.36
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.057
A549 Cytotoxicity:	0.008	Hek293 Cytotoxicity:	0.095
BCF:	0.867 ? 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:	3.577 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.883 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.597 ? 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	=	56.0	%	Open TG-GATES in vivo data: Biochemistry
NPT2	Others	Unspecified	n.a.	Inhibition	=	44.0	%	PMID[19231864]
NPT2	Others	Unspecified	n.a.	Inhibition	=	14.0	%	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 NPC28205 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	36813
0.1-0.2	12073
0.2-0.3	711
0.3-0.4	136
0.4-0.5	79
0.5-0.6	32
0.6-0.7	8
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9189	High Similarity	NPC274290
0.8947	High Similarity	NPC187777
0.7381	Intermediate Similarity	NPC54766
0.6905	Remote Similarity	NPC179764
0.6818	Remote Similarity	NPC129458
0.6757	Remote Similarity	NPC73245
0.6596	Remote Similarity	NPC225066
0.6522	Remote Similarity	NPC45626
0.6364	Remote Similarity	NPC473863
0.6087	Remote Similarity	NPC303765
0.6087	Remote Similarity	NPC226592
0.5814	Remote Similarity	NPC225929
0.5745	Remote Similarity	NPC267817
0.5641	Remote Similarity	NPC129972
0.5641	Remote Similarity	NPC301528
0.5641	Remote Similarity	NPC71317
0.5641	Remote Similarity	NPC163746
0.5641	Remote Similarity	NPC103286
0.5625	Remote Similarity	NPC470410
0.5625	Remote Similarity	NPC470412
0.5581	Remote Similarity	NPC18357
0.55	Remote Similarity	NPC196831
0.5385	Remote Similarity	NPC281245
0.525	Remote Similarity	NPC424
0.525	Remote Similarity	NPC36061
0.525	Remote Similarity	NPC69510
0.525	Remote Similarity	NPC77272
0.525	Remote Similarity	NPC8219
0.525	Remote Similarity	NPC290563
0.525	Remote Similarity	NPC139029
0.525	Remote Similarity	NPC281972
0.525	Remote Similarity	NPC92114
0.525	Remote Similarity	NPC261831
0.525	Remote Similarity	NPC87564
0.5208	Remote Similarity	NPC10081
0.52	Remote Similarity	NPC329819
0.5122	Remote Similarity	NPC95145
0.5122	Remote Similarity	NPC325642
0.5122	Remote Similarity	NPC65174
0.5116	Remote Similarity	NPC42304
0.5111	Remote Similarity	NPC284212
0.5102	Remote Similarity	NPC470320
0.5102	Remote Similarity	NPC235242

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC28205 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6828
0.1-0.2	2163
0.2-0.3	128
0.3-0.4	18
0.4-0.5	10
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
0.525	Remote Similarity	NPD3195	Phase 2
0.525	Remote Similarity	NPD3196	Approved

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