NPASS Compound

Structure

NPC473872 OpenBabel07101719522D 44 43 0 0 0 0 0 0 0 0999 V2000 1.5000 -1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 -2.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -3.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 28.5167 -1.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 28.1506 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 26.7846 -0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.8923 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 15.7583 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 14.0263 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 16.6244 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 13.1603 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 17.4904 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 12.2942 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 18.3564 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 11.4282 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 19.2224 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 10.5622 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 20.0885 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 9.6962 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 20.9545 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.8301 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 21.8205 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9641 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 22.6865 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0981 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 23.5526 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5000 -2.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 27.1506 -2.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2321 -4.4641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 24.4186 -3.9641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0000 -3.5981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 26.1506 -2.2321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5000 -2.7321 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 27.6506 -1.3660 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 3.6340 -4.9641 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0000 -5.3301 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0 26.6506 -4.8301 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 27.0167 -3.4641 0.0000 O 0 5 0 0 0 0 0 0 0 0 0 0 5.3660 -3.9641 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 25.2846 -4.4641 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0000 -3.5981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 25.6506 -3.0981 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5000 -4.4641 0.0000 P 0 0 3 0 0 0 0 0 0 0 0 0 26.1506 -3.9641 0.0000 P 0 0 3 0 0 0 0 0 0 0 0 0 1 33 1 0 0 0 0 2 33 1 0 0 0 0 3 33 1 0 0 0 0 4 34 1 0 0 0 0 5 34 1 0 0 0 0 6 34 1 0 0 0 0 7 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 14 1 0 0 0 0 13 15 1 0 0 0 0 14 16 1 0 0 0 0 15 17 1 0 0 0 0 16 18 1 0 0 0 0 17 19 1 0 0 0 0 18 20 1 0 0 0 0 19 21 1 0 0 0 0 20 22 1 0 0 0 0 21 23 1 0 0 0 0 22 24 1 0 0 0 0 23 25 1 0 0 0 0 24 26 1 0 0 0 0 25 29 1 0 0 0 0 26 30 1 0 0 0 0 27 31 1 0 0 0 0 27 33 1 0 0 0 0 28 32 1 0 0 0 0 28 34 1 0 0 0 0 29 39 1 0 0 0 0 30 40 1 0 0 0 0 31 41 1 0 0 0 0 32 42 1 0 0 0 0 35 43 2 0 0 0 0 36 43 1 0 0 0 0 37 44 2 0 0 0 0 38 44 1 0 0 0 0 39 43 1 0 0 0 0 40 44 1 0 0 0 0 41 43 1 0 0 0 0 42 44 1 0 0 0 0 M CHG 4 33 1 34 1 36 -1 38 -1 M END $$$$

Physi-Chem Properties

Molecular Weight:	672.46
Volume:	693.998
LogP:	1.974
LogD:	0.65
LogS:	-0.312
# Rotatable Bonds:	33
TPSA:	117.18
# H-Bond Aceptor:	10
# H-Bond Donor:	0
# Rings:	0
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.041
Synthetic Accessibility Score:	3.933
Fsp3:	1.0
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	3
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.522
MDCK Permeability:	1.199819325847784e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.976
Human Intestinal Absorption (HIA):	0.994
20% Bioavailability (F20%):	0.995
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0
Plasma Protein Binding (PPB):	92.9150161743164%
Volume Distribution (VD):	-0.019
Pgp-substrate:	13.84450626373291%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.972
CYP2C19-inhibitor:	0.179
CYP2C19-substrate:	0.055
CYP2C9-inhibitor:	0.033
CYP2C9-substrate:	0.911
CYP2D6-inhibitor:	0.002
CYP2D6-substrate:	0.916
CYP3A4-inhibitor:	0.711
CYP3A4-substrate:	0.004

ADMET: Excretion

Clearance (CL):	2.533
Half-life (T1/2):	0.858

ADMET: Toxicity

hERG Blockers:	0.233
Human Hepatotoxicity (H-HT):	0.335
Drug-inuced Liver Injury (DILI):	0.002
AMES Toxicity:	0.038
Rat Oral Acute Toxicity:	0.189
Maximum Recommended Daily Dose:	0.888
Skin Sensitization:	0.927
Carcinogencity:	0.291
Eye Corrosion:	0.955
Eye Irritation:	0.081
Respiratory Toxicity:	0.585

Download Data

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

Natural Product: NPC473872

Natural Product ID:	NPC473872
*Common Name:**	1,22-Bis[{[(Trimethylammonium)Ethoxy]Phosphinyl}Oxy]Docosane Hydrochloride
IUPAC Name:	22-[oxido-[2-(trimethylazaniumyl)ethoxy]phosphoryl]oxydocosyl 2-(trimethylazaniumyl)ethyl phosphate;hydrochloride
Synonyms:	1,22-Bis[{[(Trimethylammonium)Ethoxy]Phosphinyl}Oxy]Docosane HCl
Standard InCHIKey:	UPXDNOXBFGEEND-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C32H70N2O8P2.ClH/c1-33(2,3)27-31-41-43(35,36)39-29-25-23-21-19-17-15-13-11-9-7-8-10-12-14-16-18-20-22-24-26-30-40-44(37,38)42-32-28-34(4,5)6;/h7-32H2,1-6H3;1H
SMILES:	[O-]P(=O)(OCC[N+](C)(C)C)OCCCCCCCCCCCCCCCCCCCCCCOP(=O)(OCC[N+](C)(C)C)[O-].Cl
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL453950
PubChem CID:	44575413
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004707] Organic nitrogen compounds [CHEMONTID:0000278] Organonitrogen compounds [CHEMONTID:0000503] Quaternary ammonium salts [CHEMONTID:0001012] Cholines [CHEMONTID:0001250] Phosphocholines

*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
NPO32695	irlbachia alata	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10395496]

☑ 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
MIC	6

Activity Type	# Activity
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	1.25	ug.mL-1	PMID[454331]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	=	0.04	ug.mL-1	PMID[454331]
NPT87	Organism	Aspergillus fumigatus	Aspergillus fumigatus	MIC	=	0.08	ug.mL-1	PMID[454331]
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	0.5	ug.mL-1	PMID[454331]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	=	0.5	ug.mL-1	PMID[454331]

☑ 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 NPC473872 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	472
0.1-0.2	26311
0.2-0.3	14350
0.3-0.4	1271
0.4-0.5	249
0.5-0.6	26
0.6-0.7	11
0.7-0.8	3
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.7458	Intermediate Similarity	NPC328786
0.7458	Intermediate Similarity	NPC474627
0.7458	Intermediate Similarity	NPC201338
0.7077	Intermediate Similarity	NPC320663
0.7077	Intermediate Similarity	NPC224700
0.6875	Remote Similarity	NPC238646
0.6765	Remote Similarity	NPC54460
0.6377	Remote Similarity	NPC169976
0.6377	Remote Similarity	NPC126366
0.6377	Remote Similarity	NPC114640
0.6377	Remote Similarity	NPC324165
0.6377	Remote Similarity	NPC170963
0.6377	Remote Similarity	NPC33267
0.6349	Remote Similarity	NPC319131
0.6197	Remote Similarity	NPC305223
0.6081	Remote Similarity	NPC325936
0.5974	Remote Similarity	NPC82799
0.5965	Remote Similarity	NPC81384
0.5965	Remote Similarity	NPC319709
0.5965	Remote Similarity	NPC289484
0.5775	Remote Similarity	NPC475930
0.5775	Remote Similarity	NPC127145
0.5714	Remote Similarity	NPC474702
0.5694	Remote Similarity	NPC474674

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 NPC473872 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	246
0.1-0.2	6082
0.2-0.3	2309
0.3-0.4	375
0.4-0.5	115
0.5-0.6	11
0.6-0.7	9
0.7-0.8	2
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9167	High Similarity	NPD4840	Approved
0.8	Intermediate Similarity	NPD6950	Discontinued
0.8	Intermediate Similarity	NPD6706	Discontinued
0.7241	Intermediate Similarity	NPD6439	Phase 3
0.7213	Intermediate Similarity	NPD6949	Clinical (unspecified phase)
0.7097	Intermediate Similarity	NPD7347	Clinical (unspecified phase)
0.7077	Intermediate Similarity	NPD8278	Approved
0.697	Remote Similarity	NPD8277	Approved
0.68	Remote Similarity	NPD5799	Discontinued
0.6667	Remote Similarity	NPD4283	Discontinued
0.6618	Remote Similarity	NPD7535	Discontinued
0.6379	Remote Similarity	NPD7348	Clinical (unspecified phase)
0.6269	Remote Similarity	NPD5380	Approved
0.5965	Remote Similarity	NPD9463	Phase 3
0.5965	Remote Similarity	NPD3211	Approved
0.5965	Remote Similarity	NPD9462	Approved
0.5789	Remote Similarity	NPD1152	Phase 2
0.566	Remote Similarity	NPD9680	Approved
0.566	Remote Similarity	NPD9681	Approved
0.566	Remote Similarity	NPD9464	Approved

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