NPASS Compound

Structure

NPC478761 OpenBabel06302215312D 26 28 0 0 0 0 0 0 0 0999 V2000 2.0814 -2.1554 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3904 -1.2044 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7213 -0.4612 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7431 -0.6691 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.3364 -1.5827 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6581 -1.4781 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3272 -2.2213 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3054 -2.0134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6144 -1.0623 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.5926 -0.8544 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2617 -1.5976 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2398 -1.3896 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5489 -0.4386 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8797 0.3046 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9016 0.0966 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2324 0.8398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2543 0.6319 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5415 1.7908 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5196 1.9988 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9745 -2.7565 0.0000 O 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 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 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 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 26 1 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 6 7 1 0 0 0 0 6 21 1 0 0 0 0 7 8 1 0 0 0 0 8 9 2 3 0 0 0 8 20 1 0 0 0 0 9 10 1 0 0 0 0 10 15 2 0 0 0 0 10 11 1 0 0 0 0 11 12 2 0 0 0 0 12 13 1 0 0 0 0 13 14 2 0 0 0 0 14 15 1 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 16 18 1 0 0 0 0 18 19 1 0 0 0 0 21 26 2 0 0 0 0 21 22 1 0 0 0 0 22 23 2 0 0 0 0 23 24 1 0 0 0 0 24 25 2 0 0 0 0 25 26 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	586.24
Volume:	577.551
LogP:	3.441
LogD:	2.144
LogS:	-4.093
# Rotatable Bonds:	8
TPSA:	147.8
# H-Bond Aceptor:	11
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.399
Synthetic Accessibility Score:	5.554
Fsp3:	0.613
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.292
MDCK Permeability:	0.00015582887863274664
Pgp-inhibitor:	1.0
Pgp-substrate:	0.945
Human Intestinal Absorption (HIA):	0.031
20% Bioavailability (F20%):	0.995
30% Bioavailability (F30%):	0.982

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.793
Plasma Protein Binding (PPB):	80.38219451904297%
Volume Distribution (VD):	1.942
Pgp-substrate:	20.565082550048828%

ADMET: Metabolism

CYP1A2-inhibitor:	0.016
CYP1A2-substrate:	0.044
CYP2C19-inhibitor:	0.299
CYP2C19-substrate:	0.126
CYP2C9-inhibitor:	0.844
CYP2C9-substrate:	0.018
CYP2D6-inhibitor:	0.07
CYP2D6-substrate:	0.044
CYP3A4-inhibitor:	0.684
CYP3A4-substrate:	0.477

ADMET: Excretion

Clearance (CL):	5.189
Half-life (T1/2):	0.037

ADMET: Toxicity

hERG Blockers:	0.248
Human Hepatotoxicity (H-HT):	0.888
Drug-inuced Liver Injury (DILI):	0.597
AMES Toxicity:	0.049
Rat Oral Acute Toxicity:	0.892
Maximum Recommended Daily Dose:	0.814
Skin Sensitization:	0.178
Carcinogencity:	0.04
Eye Corrosion:	0.004
Eye Irritation:	0.008
Respiratory Toxicity:	0.975

Download Data

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

Natural Product: NPC478761

Natural Product ID:	NPC478761
*Common Name:**	XNNQOCQYCYSTLO-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	XNNQOCQYCYSTLO-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H20N2O4/c1-3-26-22-13-14(15-8-5-7-11-18(15)22)12-19(23)21-17-10-6-4-9-16(17)20(24)25-2/h4-11,13H,3,12H2,1-2H3,(H,21,23)
SMILES:	CCOn1cc(CC(=Nc2ccccc2C(=O)OC)O)c2ccccc12
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
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	Roots	n.a.	n.a.	PMID[32004936]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4554	Isatis tinctoria	Species	Brassicaceae	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
EC50	1
Others	3

Activity Type	# Activity
Cell Line	2
Organism	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2615	Cell Line	HEK-293T	Homo sapiens	CC50	>	30000.0	nM	PMID[32004936]
NPT2615	Cell Line	HEK-293T	Homo sapiens	Activity	=	52.76	%	PMID[32004936]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	5700.0	nM	PMID[32004936]
NPT2	Others	Unspecified		Ratio CC50/EC50	>	5.26	n.a.	PMID[32004936]

☑ 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 NPC478761 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	295
0.1-0.2	2144
0.2-0.3	10306
0.3-0.4	11604
0.4-0.5	13017
0.5-0.6	2411
0.6-0.7	2169
0.7-0.8	714
0.8-0.85	24
0.85-0.9	3
0.9-0.95	2
0.95-1	8

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 NPC478761 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	180
0.1-0.2	597
0.2-0.3	790
0.3-0.4	1213
0.4-0.5	2689
0.5-0.6	2309
0.6-0.7	1140
0.7-0.8	220
0.8-0.85	12
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