NPASS Compound

Natural Product: NPC250954

Natural Product ID	NPC250954
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Lachnophyllum Ester
IUPAC Name	methyl (E)-dec-2-en-4,6-diynoate
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL2269913
PubChem CID	642290
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0003909] Fatty Acyls [CHEMONTID:0000324] Fatty acid esters

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 25 24 0 0 0 0 0 0 0 0999 V2000 4.3450 1.8765 0.4187 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9436 0.4911 0.3884 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4868 -0.2249 -0.8629 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0328 -0.2958 -0.8150 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8120 -0.3401 -0.7895 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4005 -0.4129 -0.7479 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8040 -0.4879 -0.7070 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2520 -0.5837 -0.6333 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8377 -0.4241 0.5357 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2996 -0.5067 0.6910 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8374 -0.3514 1.8142 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.0767 -0.7563 -0.4079 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4850 -0.8392 -0.2775 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9187 2.5552 1.0908 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2753 1.8813 0.6413 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4805 2.2948 -0.6158 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0520 0.6208 0.3090 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6704 -0.0302 1.3056 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9494 -1.2317 -0.9257 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8162 0.3508 -1.7520 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8396 -0.7808 -1.5120 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2044 -0.2267 1.3965 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8940 0.0253 0.3175 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9258 -0.8229 -1.3005 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7272 -1.7806 0.2183 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 3 0 5 6 1 0 6 7 3 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 1 14 1 0 1 15 1 0 1 16 1 0 2 17 1 0 2 18 1 0 3 19 1 0 3 20 1 0 8 21 1 0 9 22 1 0 13 23 1 0 13 24 1 0 13 25 1 0 M END

Standard InCHIKey	LWONXTYZMYZRSU-MDZDMXLPSA-N
Standard InCHI	InChI=1S/C11H12O2/c1-3-4-5-6-7-8-9-10-11(12)13-2/h9-10H,3-4H2,1-2H3/b10-9+
SMILES	CCCC#CC#C/C=C/C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	176.08	Volume:	200.574 ? Van der Waals volume.
Dense:	0.878	LogP:	2.659 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.505 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.729 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	4.0
TPSA:	26.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	0.0	Rings:	0.0
Heavy Atoms:	2.0

MedChem Properties

QED Drug-Likeness Score:	0.362	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.343	Fsp³:	0.364
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:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.009	Fluc inhibitor:	0.064 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.059 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.081 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.996	Promiscuous compounds:	0.031

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.542	MDCK Permeability:	-4.504
Pgp-inhibitor:	0.704	Pgp-substrate:	0.002
PAMPA:	0.916 ? 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):	0.131
20% Bioavailability (F20%):	0.013	30% Bioavailability (F30%):	0.011
50% Bioavailability (F50%):	0.936

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.003
Plasma Protein Binding (PPB):	98.653%	Volume Distribution (VD):	0.073
Fu:	0.525% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.116
OATP1B3 inhibitor:	0.317	BCRP inhibitor:	0.829
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.995
CYP2C19-inhibitor:	0.033	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.996	CYP2C9-substrate:	0.016
CYP2D6-inhibitor:	0.133	CYP2D6-substrate:	0.97
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.011 ? 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):

6.755

Half-life (T1/2):

1.363

ADMET: Toxicity

hERG Blockers:	0.095	hERG Blockers (10um):	0.524
Human Hepatotoxicity (H-HT):	0.58	Drug-induced Liver Injury (DILI):	0.865
AMES Toxicity:	0.425	Rat Oral Acute Toxicity:	0.467
Maximum Recommended Daily Dose:	0.62	Skin Sensitization:	0.658
Carcinogencity:	0.447	Eye Corrosion:	0.988
Eye Irritation:	0.992	Respiratory Toxicity:	0.958
Drug-induced Neurotoxicity:	0.449	Ototoxicity:	0.377
Hematotoxicity:	0.165	Drug-induced Nephrotoxicity:	0.208
Genotoxicity:	0.041	RPMI-8226 Immunitoxicity:	0.051
A549 Cytotoxicity:	0.031	Hek293 Cytotoxicity:	0.233
BCF:	1.096 ? 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:	3.779 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.14 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.792 ? 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
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20121251]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[22612410]
NPO60360	Erigeron bonariensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36671701]
NPO50341	Salsola imbricata	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36671701]
NPO47426	Erigeron canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36671701]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38792265]
NPO50341	Salsola imbricata	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39711973]
NPO23934	Hymeniacidon hauraki	Species	Halichondriidae	Eukaryota	n.a.	New Zealand	n.a.	PMID[7853004]
NPO3203	Clibadium surinamense	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4519	Bergia capensis	Species	Elatinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23303	Drimiopsis maculata	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23934	Hymeniacidon hauraki	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO3891	Lycopodium varium	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24261	Mikania pohlii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23430	Prinsepia uniflora	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50341	Salsola imbricata	Species	Chenopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO12088	Conyza canadensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23430	Prinsepia uniflora	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23934	Hymeniacidon hauraki	Species	Halichondriidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4519	Bergia capensis	Species	Elatinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23303	Drimiopsis maculata	Species	Hyacinthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3203	Clibadium surinamense	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3891	Lycopodium varium	Species	Lycopodiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24261	Mikania pohlii	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12088	Conyza canadensis	Species	Asteraceae	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
NPO12088	Conyza canadensis	Oil	Flowers	10.9	n.a.	n.a.	%	PMID[38792265]
NPO12088	Conyza canadensis	Oil	Leaves	3.45	n.a.	n.a.	%	PMID[38792265]
NPO12088	Conyza canadensis	Oil	Stems	4.01	n.a.	n.a.	%	PMID[38792265]
NPO47426	Erigeron canadensis	Oil	n.a.	16.3	n.a.	n.a.	%	PMID[36671701]
NPO50341	Salsola imbricata	Oil	n.a.	0.1	n.a.	n.a.	%	PMID[36671701]
NPO60360	Erigeron bonariensis	Oil	n.a.	24.9	n.a.	n.a.	%	PMID[36671701]

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
FR50	1

Activity Type	# Activity
Organism	1

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
NPT776	Organism	Spodoptera littoralis	Spodoptera littoralis	FR50	=	0.31	n.a.	DOI[10.1016/S0305-1978(98)00131-8]

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	=	5.0	ppm	DOI[10.1016/S0305-1978(98)00131-8]

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 NPC250954 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	29175
0.1-0.2	20131
0.2-0.3	503
0.3-0.4	41
0.4-0.5	7
0.5-0.6	0
0.6-0.7	1
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
0.6667	Remote Similarity	NPC297608

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC250954 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7471
0.1-0.2	1657
0.2-0.3	21
0.3-0.4	0
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