NPASS Compound

Structure

NPC66365 OpenBabel07101718182D 29 29 0 0 0 0 0 0 0 0999 V2000 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -12.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -7.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -6.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -7.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -5.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -8.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -4.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -9.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -4.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -10.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -11.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -12.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 0.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -10.5000 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 1 17 1 0 0 0 0 2 18 1 0 0 0 0 3 19 1 0 0 0 0 4 26 1 0 0 0 0 5 27 1 0 0 0 0 6 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 10 1 0 0 0 0 9 11 1 0 0 0 0 10 12 1 0 0 0 0 11 13 1 0 0 0 0 12 16 1 0 0 0 0 13 17 1 0 0 0 0 14 15 1 0 0 0 0 14 17 2 0 0 0 0 15 20 1 0 0 0 0 16 29 1 0 0 0 0 18 20 2 0 0 0 0 18 21 1 0 0 0 0 19 24 2 0 0 0 0 19 29 1 0 0 0 0 20 28 1 0 0 0 0 21 22 1 0 0 0 0 21 25 2 0 0 0 0 22 23 2 0 0 0 0 22 26 1 0 0 0 0 23 27 1 0 0 0 0 23 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	424.23
Volume:	447.086
LogP:	5.331
LogD:	4.532
LogS:	-5.299
# Rotatable Bonds:	15
TPSA:	65.74
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	1
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.275
Synthetic Accessibility Score:	3.147
Fsp3:	0.652
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.61
MDCK Permeability:	2.1026628019171767e-05
Pgp-inhibitor:	0.047
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.021
20% Bioavailability (F20%):	0.016
30% Bioavailability (F30%):	0.733

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.46
Plasma Protein Binding (PPB):	96.43036651611328%
Volume Distribution (VD):	1.581
Pgp-substrate:	1.2449779510498047%

ADMET: Metabolism

CYP1A2-inhibitor:	0.738
CYP1A2-substrate:	0.825
CYP2C19-inhibitor:	0.795
CYP2C19-substrate:	0.638
CYP2C9-inhibitor:	0.754
CYP2C9-substrate:	0.921
CYP2D6-inhibitor:	0.344
CYP2D6-substrate:	0.772
CYP3A4-inhibitor:	0.755
CYP3A4-substrate:	0.135

ADMET: Excretion

Clearance (CL):	4.604
Half-life (T1/2):	0.219

ADMET: Toxicity

hERG Blockers:	0.004
Human Hepatotoxicity (H-HT):	0.946
Drug-inuced Liver Injury (DILI):	0.961
AMES Toxicity:	0.031
Rat Oral Acute Toxicity:	0.011
Maximum Recommended Daily Dose:	0.116
Skin Sensitization:	0.954
Carcinogencity:	0.058
Eye Corrosion:	0.028
Eye Irritation:	0.42
Respiratory Toxicity:	0.043

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC66365

Natural Product ID:	NPC66365
*Common Name:**	Lehualide C
IUPAC Name:	S-[(E)-12-(5,6-dimethoxy-3-methyl-4-oxopyran-2-yl)-10-methyldodec-10-enyl] ethanethioate
Synonyms:	Lehualide C
Standard InCHIKey:	JETGOHMWHVGCPY-SAPNQHFASA-N
Standard InCHI:	InChI=1S/C23H36O5S/c1-17(13-11-9-7-6-8-10-12-16-29-19(3)24)14-15-20-18(2)21(25)22(26-4)23(27-5)28-20/h14H,6-13,15-16H2,1-5H3/b17-14+
SMILES:	COc1oc(C/C=C(/CCCCCCCCCSC(=O)C)C)c(c(=O)c1OC)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL463505
PubChem CID:	11604251
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000086] Pyrans [CHEMONTID:0000481] Pyranones and derivatives

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO31509	Plakortis	Genus	Plakinidae	Eukaryota	n.a.	Hawaiian	n.a.	PMID[16180823]
NPO31509	Plakortis	Genus	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21351759]

☑ 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	NP ID	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
LD50	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT140	Organism	Artemia	Artemia	LD50	=	15.0	ug ml-1	PMID[483141]

☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC66365 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	358
0.1-0.2	1941
0.2-0.3	5814
0.3-0.4	11502
0.4-0.5	7990
0.5-0.6	7235
0.6-0.7	7624
0.7-0.8	228
0.8-0.85	1
0.85-0.9	2
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9254	High Similarity	NPC134593
0.7125	Intermediate Similarity	NPC47069
0.7	Intermediate Similarity	NPC224103
0.7	Intermediate Similarity	NPC261732
0.7	Intermediate Similarity	NPC299369
0.7	Intermediate Similarity	NPC200831
0.6842	Remote Similarity	NPC474619
0.6812	Remote Similarity	NPC317796
0.68	Remote Similarity	NPC98897
0.6711	Remote Similarity	NPC16119
0.6667	Remote Similarity	NPC474400
0.6667	Remote Similarity	NPC34622
0.6618	Remote Similarity	NPC22329
0.6582	Remote Similarity	NPC291062
0.6582	Remote Similarity	NPC94743
0.6538	Remote Similarity	NPC146376
0.6538	Remote Similarity	NPC134385
0.6538	Remote Similarity	NPC263382
0.6538	Remote Similarity	NPC125578
0.6533	Remote Similarity	NPC151728
0.6533	Remote Similarity	NPC57463
0.65	Remote Similarity	NPC474539
0.6471	Remote Similarity	NPC220191
0.6456	Remote Similarity	NPC262673
0.6429	Remote Similarity	NPC474805
0.641	Remote Similarity	NPC243272
0.6364	Remote Similarity	NPC7940
0.6351	Remote Similarity	NPC473494
0.6341	Remote Similarity	NPC264178
0.6338	Remote Similarity	NPC129710
0.625	Remote Similarity	NPC94488
0.625	Remote Similarity	NPC317548
0.6216	Remote Similarity	NPC139056
0.6145	Remote Similarity	NPC147438
0.6129	Remote Similarity	NPC108026
0.6118	Remote Similarity	NPC471225
0.6071	Remote Similarity	NPC315552
0.6026	Remote Similarity	NPC7029
0.6024	Remote Similarity	NPC316851
0.6	Remote Similarity	NPC26504
0.5897	Remote Similarity	NPC477830
0.5897	Remote Similarity	NPC143168
0.5897	Remote Similarity	NPC53109
0.5823	Remote Similarity	NPC477457
0.5823	Remote Similarity	NPC475618
0.5823	Remote Similarity	NPC477456
0.5802	Remote Similarity	NPC298249
0.5753	Remote Similarity	NPC168521
0.575	Remote Similarity	NPC471556
0.5747	Remote Similarity	NPC473536
0.5735	Remote Similarity	NPC106547
0.5714	Remote Similarity	NPC288281
0.5652	Remote Similarity	NPC191337
0.5652	Remote Similarity	NPC110396
0.5641	Remote Similarity	NPC79756
0.5632	Remote Similarity	NPC477708
0.5618	Remote Similarity	NPC471740
0.5616	Remote Similarity	NPC137396
0.5616	Remote Similarity	NPC477779
0.561	Remote Similarity	NPC203335
0.561	Remote Similarity	NPC251429

Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC66365 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	320
0.1-0.2	1009
0.2-0.3	2233
0.3-0.4	2882
0.4-0.5	1807
0.5-0.6	692
0.6-0.7	200
0.7-0.8	7
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
0.7	Intermediate Similarity	NPD8779	Phase 3
0.6711	Remote Similarity	NPD6108	Clinical (unspecified phase)
0.6118	Remote Similarity	NPD4756	Discovery
0.6076	Remote Similarity	NPD3704	Approved
0.5897	Remote Similarity	NPD2664	Clinical (unspecified phase)
0.587	Remote Similarity	NPD6422	Discontinued

Bioactivity similarity: Similar Natural Products in NPASS

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