NPASS Compound

Structure

NPC485112 OpenBabel06302215112D 25 27 0 0 1 0 0 0 0 0999 V2000 0.8660 -3.5000 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 1.7321 -2.0000 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 -0.5000 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 1.7321 1.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 3.4641 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9641 -0.8660 0.0000 C 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 1.7321 2.0000 0.0000 O 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 2.5000 0.0000 O 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 -0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -0.5000 0.0000 O 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 -1.7321 1.0000 0.0000 O 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 -1.7321 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 -3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 2 0 0 0 0 2 25 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 18 1 0 0 0 0 5 6 2 0 0 0 0 6 13 1 0 0 0 0 6 7 1 0 0 0 0 7 14 1 0 0 0 0 7 8 1 0 0 0 0 7 15 1 0 0 0 0 8 9 1 0 0 0 0 8 14 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 10 12 1 0 0 0 0 10 13 1 0 0 0 0 15 16 2 0 0 0 0 15 17 1 0 0 0 0 17 18 2 0 0 0 0 17 20 1 0 0 0 0 18 19 1 0 0 0 0 20 21 2 0 0 0 0 20 22 1 0 0 0 0 22 23 1 0 0 0 0 22 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	346.18
Volume:	359.576
LogP:	3.836
LogD:	1.416
LogS:	-3.685
# Rotatable Bonds:	4
TPSA:	72.97
# H-Bond Aceptor:	5
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.444
Synthetic Accessibility Score:	5.19
Fsp3:	0.65
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.806
MDCK Permeability:	2.3620033971383236e-05
Pgp-inhibitor:	0.576
Pgp-substrate:	0.013
Human Intestinal Absorption (HIA):	0.063
20% Bioavailability (F20%):	0.67
30% Bioavailability (F30%):	0.54

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.177
Plasma Protein Binding (PPB):	93.02357482910156%
Volume Distribution (VD):	2.596
Pgp-substrate:	4.978827953338623%

ADMET: Metabolism

CYP1A2-inhibitor:	0.024
CYP1A2-substrate:	0.234
CYP2C19-inhibitor:	0.168
CYP2C19-substrate:	0.894
CYP2C9-inhibitor:	0.055
CYP2C9-substrate:	0.037
CYP2D6-inhibitor:	0.009
CYP2D6-substrate:	0.082
CYP3A4-inhibitor:	0.354
CYP3A4-substrate:	0.716

ADMET: Excretion

Clearance (CL):	12.113
Half-life (T1/2):	0.123

ADMET: Toxicity

hERG Blockers:	0.012
Human Hepatotoxicity (H-HT):	0.201
Drug-inuced Liver Injury (DILI):	0.955
AMES Toxicity:	0.01
Rat Oral Acute Toxicity:	0.988
Maximum Recommended Daily Dose:	0.026
Skin Sensitization:	0.414
Carcinogencity:	0.268
Eye Corrosion:	0.092
Eye Irritation:	0.057
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC485112

Natural Product ID:	NPC485112
*Common Name:**	PMCJEJDMLWMLKT-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	PMCJEJDMLWMLKT-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H26O5/c1-10(2)7-8-12-16(22)14(15(21)11(3)4)17(23)20-13(24-20)9-19(5,6)25-18(12)20/h7,11,13,22H,8-9H2,1-6H3
SMILES:	CC(=CCC1=C2C3(C(CC(C)(C)O2)O3)C(=O)C(=C1O)C(=O)C(C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	127040507
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002943] Dioxepanes [CHEMONTID:0002946] 1,4-dioxepanes

*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
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26469557]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[2681536]
NPO2575	Psorothamnus fremontii	Species	Fabaceae	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	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
IC50	11

Activity Type	# Activity
Cell Line	3
Organism	8

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT189	Cell Line	Vero	Chlorocebus aethiops	IC50	=	21.0	ug.mL-1	PMID[26469557]
NPT857	Cell Line	LLC-PK1	Sus scrofa	IC50	=	30.0	ug.mL-1	PMID[26469557]
NPT65	Cell Line	HepG2	Homo sapiens	IC50	=	31.0	ug.mL-1	PMID[26469557]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	2.4	ug.mL-1	PMID[26469557]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	1.4	ug.mL-1	PMID[26469557]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	8.8	ug.mL-1	PMID[26469557]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	8.6	ug.mL-1	PMID[26469557]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IC50	=	1.6	ug.mL-1	PMID[26469557]
NPT1204	Organism	Enterococcus faecalis ATCC 29212	Enterococcus faecalis ATCC 29212	IC50	=	5.3	ug.mL-1	PMID[26469557]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	IC50	=	2.8	ug.mL-1	PMID[26469557]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	IC50	=	1.6	ug.mL-1	PMID[26469557]

☑ 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 NPC485112 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	216
0.1-0.2	1253
0.2-0.3	3974
0.3-0.4	7885
0.4-0.5	15335
0.5-0.6	10203
0.6-0.7	3337
0.7-0.8	479
0.8-0.85	12
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID

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 NPC485112 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	191
0.1-0.2	1496
0.2-0.3	3486
0.3-0.4	2594
0.4-0.5	998
0.5-0.6	308
0.6-0.7	75
0.7-0.8	2
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

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