NPASS Compound

Structure

NPC480753 OpenBabel06302216152D 33 38 0 0 1 0 0 0 0 0999 V2000 4.7250 -6.1745 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0179 -5.4674 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2767 -4.5015 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5696 -3.7944 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8284 -2.8284 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7944 -2.5696 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5015 -3.2767 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2426 -4.2426 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9497 -4.9497 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6909 -5.9157 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4674 -3.0179 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.1745 -3.7250 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1213 -2.1213 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 2.1554 -2.3801 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8966 -3.3461 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9306 -3.6049 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2235 -2.8978 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4824 -1.9319 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4483 -1.6730 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7071 -0.7071 0.0000 N 0 0 0 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 0.0000 0.0000 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 1.0000 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6730 -0.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3801 -1.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2711 -0.7014 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1622 -1.1554 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1147 0.2863 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1270 0.4427 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6675 -3.3518 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5110 -4.3395 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4767 -4.4959 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 8 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 6 1 0 0 0 0 5 13 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 7 11 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 11 12 1 0 0 0 0 13 26 1 0 0 0 0 13 14 1 0 0 0 0 14 19 2 0 0 0 0 14 15 1 0 0 0 0 15 16 2 0 0 0 0 16 33 1 0 0 0 0 16 17 1 0 0 0 0 17 18 2 0 0 0 0 17 31 1 0 0 0 0 18 19 1 0 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 20 25 1 0 0 0 0 21 24 1 0 0 0 0 21 22 1 0 0 0 0 22 23 1 0 0 0 0 23 24 1 0 0 0 0 25 30 1 0 0 0 0 25 26 2 0 0 0 0 26 27 1 0 0 0 0 27 28 2 0 0 0 0 27 29 1 0 0 0 0 29 30 1 0 0 0 0 31 32 1 0 0 0 0 32 33 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	451.16
Volume:	441.054
LogP:	4.477
LogD:	3.947
LogS:	-5.258
# Rotatable Bonds:	5
TPSA:	82.76
# H-Bond Aceptor:	8
# H-Bond Donor:	1
# Rings:	6
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.585
Synthetic Accessibility Score:	3.465
Fsp3:	0.36
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.903
MDCK Permeability:	2.262360430904664e-05
Pgp-inhibitor:	0.066
Pgp-substrate:	0.112
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.007
30% Bioavailability (F30%):	0.023

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.012
Plasma Protein Binding (PPB):	98.76065826416016%
Volume Distribution (VD):	0.9
Pgp-substrate:	1.208188533782959%

ADMET: Metabolism

CYP1A2-inhibitor:	0.072
CYP1A2-substrate:	0.919
CYP2C19-inhibitor:	0.898
CYP2C19-substrate:	0.938
CYP2C9-inhibitor:	0.833
CYP2C9-substrate:	0.923
CYP2D6-inhibitor:	0.498
CYP2D6-substrate:	0.85
CYP3A4-inhibitor:	0.894
CYP3A4-substrate:	0.929

ADMET: Excretion

Clearance (CL):	11.362
Half-life (T1/2):	0.143

ADMET: Toxicity

hERG Blockers:	0.017
Human Hepatotoxicity (H-HT):	0.489
Drug-inuced Liver Injury (DILI):	0.924
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.673
Maximum Recommended Daily Dose:	0.981
Skin Sensitization:	0.862
Carcinogencity:	0.28
Eye Corrosion:	0.003
Eye Irritation:	0.185
Respiratory Toxicity:	0.911

Download Data

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

Natural Product: NPC480753

Natural Product ID:	NPC480753
*Common Name:**	VIJOCQSCQNRGHD-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	VIJOCQSCQNRGHD-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C25H25NO7/c1-28-20-7-13(8-21(29-2)24(20)30-3)22-15-9-18-19(33-12-32-18)10-16(15)26(14-5-4-6-14)17-11-31-25(27)23(17)22/h7-10,14,22H,4-6,11-12H2,1-3H3
SMILES:	COc1cc(cc(c1OC)OC)C1c2cc3c(cc2N(C2CCC2)C2=C1C(=O)OC2)OCO3
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	127043785
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001253] Quinolines and derivatives [CHEMONTID:0002348] Phenylquinolines

*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
NPO28528	Bridelia ferruginea	Species	Phyllanthaceae	Eukaryota	roots	Gabon	1987	PMID[18327911]
NPO28528	Bridelia ferruginea	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[18327911]
NPO28528	Bridelia ferruginea	Species	Phyllanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[26938998]
NPO28528	Bridelia ferruginea	Species	Phyllanthaceae	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
ED50	1
GI50	6

Activity Type	# Activity
Cell Line	3
NON-MOLECULAR	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT168	Cell Line	P388	Mus musculus	ED50	=	0.24	ug ml-1	PMID[26938998]
NPT83	Cell Line	MCF7	Homo sapiens	GI50	=	0.026	ug.mL-1	PMID[26938998]
NPT397	Cell Line	NCI-H460	Homo sapiens	GI50	=	0.028	ug.mL-1	PMID[26938998]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	0.04	ug.mL-1	PMID[26938998]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	0.026	ug.mL-1	PMID[26938998]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	0.032	ug.mL-1	PMID[26938998]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	GI50	=	0.047	ug.mL-1	PMID[26938998]

☑ 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 NPC480753 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	355
0.1-0.2	1916
0.2-0.3	7615
0.3-0.4	10165
0.4-0.5	8113
0.5-0.6	12570
0.6-0.7	1759
0.7-0.8	179
0.8-0.85	5
0.85-0.9	7
0.9-0.95	7
0.95-1	6

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 NPC480753 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	227
0.1-0.2	684
0.2-0.3	1042
0.3-0.4	1996
0.4-0.5	2802
0.5-0.6	1957
0.6-0.7	426
0.7-0.8	15
0.8-0.85	1
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