NPASS Compound

Structure

NPC489647 OpenBabel06302216112D 29 31 0 0 1 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 2.5981 -1.5000 0.0000 C 0 0 0 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 4.3301 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -1.0000 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 5.3007 -0.0055 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2788 0.2024 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7788 -0.6636 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7734 -0.7681 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1097 -1.4067 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5575 0.6637 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 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0000 -2.0000 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 -1.7321 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.0981 -0.6340 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0981 -2.3660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 2 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 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.0000 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 O 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 12 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 10 1 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 6 11 1 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 8 10 1 0 0 0 0 12 13 1 0 0 0 0 14 13 1 6 0 0 0 14 15 1 0 0 0 0 14 27 1 0 0 0 0 15 24 1 0 0 0 0 15 16 1 6 0 0 0 15 17 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 20 21 1 6 0 0 0 20 22 1 0 0 0 0 20 24 1 0 0 0 0 22 23 1 0 0 0 0 24 25 1 6 0 0 0 25 26 1 0 0 0 0 26 27 1 0 0 0 0 27 28 1 6 0 0 0 27 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	404.29
Volume:	442.538
LogP:	4.306
LogD:	4.22
LogS:	-4.589
# Rotatable Bonds:	6
TPSA:	73.83
# H-Bond Aceptor:	4
# H-Bond Donor:	3
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.545
Synthetic Accessibility Score:	4.708
Fsp3:	0.76
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.907
MDCK Permeability:	2.4381324692512862e-05
Pgp-inhibitor:	0.032
Pgp-substrate:	0.004
Human Intestinal Absorption (HIA):	0.016
20% Bioavailability (F20%):	0.055
30% Bioavailability (F30%):	0.927

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.184
Plasma Protein Binding (PPB):	96.48416900634766%
Volume Distribution (VD):	1.375
Pgp-substrate:	3.2592973709106445%

ADMET: Metabolism

CYP1A2-inhibitor:	0.042
CYP1A2-substrate:	0.446
CYP2C19-inhibitor:	0.074
CYP2C19-substrate:	0.815
CYP2C9-inhibitor:	0.196
CYP2C9-substrate:	0.736
CYP2D6-inhibitor:	0.147
CYP2D6-substrate:	0.529
CYP3A4-inhibitor:	0.517
CYP3A4-substrate:	0.195

ADMET: Excretion

Clearance (CL):	7.273
Half-life (T1/2):	0.543

ADMET: Toxicity

hERG Blockers:	0.021
Human Hepatotoxicity (H-HT):	0.173
Drug-inuced Liver Injury (DILI):	0.185
AMES Toxicity:	0.005
Rat Oral Acute Toxicity:	0.009
Maximum Recommended Daily Dose:	0.078
Skin Sensitization:	0.56
Carcinogencity:	0.016
Eye Corrosion:	0.007
Eye Irritation:	0.145
Respiratory Toxicity:	0.626

Download Data

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

Natural Product: NPC489647

Natural Product ID:	NPC489647
*Common Name:**	KHIDSVXJRBGIHK-DUTCEVNASA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	KHIDSVXJRBGIHK-DUTCEVNASA-N
Standard InCHI:	InChI=1S/C25H40O4/c1-17(7-9-19-18(2)15-22(27)29-19)8-10-21-24(4)13-6-12-23(3,16-26)20(24)11-14-25(21,5)28/h7,15,19-21,26,28H,6,8-14,16H2,1-5H3/b17-7+/t19?,20-,21+,23-,24-,25+/m0/s1
SMILES:	C/C(=CCC1C(=CC(=O)O1)C)/CC[C@@H]1[C@@]2(C)CCC[C@@](C)(CO)[C@@H]2CC[C@@]1(C)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds]

*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
NPO40338	Salvia tingitana	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[32182064]

☑ 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	22

Activity Type	# Activity
Organism	22

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	317000.0	nM	PMID[32182064]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	=	317000.0	nM	PMID[32182064]
NPT17	Organism	Staphylococcus epidermidis	Staphylococcus epidermidis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT1863	Organism	Staphylococcus saprophyticus	Staphylococcus saprophyticus	MIC	=	317000.0	nM	PMID[32182064]
NPT3599	Organism	Staphylococcus capitis	Staphylococcus capitis	MIC	=	317000.0	nM	PMID[32182064]
NPT5312	Organism	Staphylococcus warneri	Staphylococcus warneri	MIC	=	317000.0	nM	PMID[32182064]
NPT4427	Organism	Staphylococcus simulans	Staphylococcus simulans	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4840	Organism	Staphylococcus lugdunensis	Staphylococcus lugdunensis	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT1477	Organism	Staphylococcus haemolyticus	Staphylococcus haemolyticus	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4025	Organism	Staphylococcus hominis	Staphylococcus hominis	MIC	=	317000.0	nM	PMID[32182064]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	317000.0	nM	PMID[32182064]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	79200.0	nM	PMID[32182064]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	158000.0	nM	PMID[32182064]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	=	317000.0	nM	PMID[32182064]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	=	158000.0	nM	PMID[32182064]
NPT4075	Organism	Enterococcus avium	Enterococcus avium	MIC	=	158000.0	nM	PMID[32182064]
NPT23872	ORGANISM	Enterococcus casseliflavus	Enterococcus casseliflavus	MIC	=	158000.0	nM	PMID[32182064]
NPT3730	Organism	Enterococcus durans	Enterococcus durans	MIC	>	128.0	ug.mL-1	PMID[32182064]
NPT4844	Organism	Enterococcus gallinarum	Enterococcus gallinarum	MIC	=	158000.0	nM	PMID[32182064]

☑ 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 NPC489647 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	179
0.1-0.2	1148
0.2-0.3	4016
0.3-0.4	10022
0.4-0.5	12332
0.5-0.6	6706
0.6-0.7	5693
0.7-0.8	2254
0.8-0.85	247
0.85-0.9	73
0.9-0.95	22
0.95-1	5

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 NPC489647 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	153
0.1-0.2	1383
0.2-0.3	3661
0.3-0.4	2551
0.4-0.5	926
0.5-0.6	208
0.6-0.7	200
0.7-0.8	64
0.8-0.85	4
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