NPASS Compound

Structure

NPC21573 OpenBabel06302215162D 22 25 0 0 1 0 0 0 0 0999 V2000 -2.0416 -2.6388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5880 -1.8433 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7974 -1.3811 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0043 -1.8390 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7883 -1.3822 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7931 -0.4579 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5884 0.0037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5876 0.9182 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7945 1.3761 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7995 2.2919 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1162 2.2969 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0072 0.9249 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8050 1.3855 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6011 0.9118 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3890 1.3713 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1809 0.9187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1849 0.0066 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3970 -0.4529 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6051 -0.0004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8073 -0.4610 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 -0.0047 -2.7565 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 20 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 4 22 1 0 0 0 0 5 6 1 0 0 0 0 6 21 2 0 0 0 0 6 7 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 9 10 1 0 0 0 0 9 12 1 0 0 0 0 10 11 2 0 0 0 0 12 13 1 1 0 0 0 12 21 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 17 1 0 0 0 0 17 18 2 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 M END $$$$

Physi-Chem Properties

Molecular Weight:	295.12
Volume:	304.571
LogP:	2.778
LogD:	2.575
LogS:	-2.89
# Rotatable Bonds:	2
TPSA:	49.77
# H-Bond Aceptor:	4
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.867
Synthetic Accessibility Score:	3.258
Fsp3:	0.278
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.561
MDCK Permeability:	2.4868080799933523e-05
Pgp-inhibitor:	0.0
Pgp-substrate:	0.974
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.01
30% Bioavailability (F30%):	0.56

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.712
Plasma Protein Binding (PPB):	88.08899688720703%
Volume Distribution (VD):	1.138
Pgp-substrate:	7.693173885345459%

ADMET: Metabolism

CYP1A2-inhibitor:	0.771
CYP1A2-substrate:	0.803
CYP2C19-inhibitor:	0.272
CYP2C19-substrate:	0.374
CYP2C9-inhibitor:	0.191
CYP2C9-substrate:	0.857
CYP2D6-inhibitor:	0.482
CYP2D6-substrate:	0.567
CYP3A4-inhibitor:	0.384
CYP3A4-substrate:	0.441

ADMET: Excretion

Clearance (CL):	2.665
Half-life (T1/2):	0.431

ADMET: Toxicity

hERG Blockers:	0.083
Human Hepatotoxicity (H-HT):	0.161
Drug-inuced Liver Injury (DILI):	0.079
AMES Toxicity:	0.539
Rat Oral Acute Toxicity:	0.121
Maximum Recommended Daily Dose:	0.961
Skin Sensitization:	0.182
Carcinogencity:	0.077
Eye Corrosion:	0.003
Eye Irritation:	0.023
Respiratory Toxicity:	0.601

Download Data

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

Natural Product: NPC21573

Natural Product ID:	NPC21573
*Common Name:**	ZHLISMCEGCAYID-CQSZACIVSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ZHLISMCEGCAYID-CQSZACIVSA-N
Standard InCHI:	InChI=1S/C18H17NO3/c1-22-18-15(21)9-12-6-7-19(10-20)14-8-11-4-2-3-5-13(11)17(18)16(12)14/h2-5,9-10,14,21H,6-8H2,1H3/t14-/m1/s1
SMILES:	COc1c(cc2CCN(C=O)[C@@H]3Cc4ccccc4-c1c23)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	46895105
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0000381] Aporphines

*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
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12081149]
NPO21709	Pinus ponderosa	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12371811]
NPO22979	Hildegardia barteri	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16378378]
NPO18288	Macaranga bicolor	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21275386]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	root	n.a.	PMID[22051934]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	aerial parts	herbal garden of Chungbuk National University, Cheongju, Korea	2012-Oct	PMID[24963714]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	aerial part	n.a.	Database[Article]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO23024	Epimedium koreanum	Species	Berberidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20153	Quercus pontica	Species	Fagaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18288	Macaranga bicolor	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21709	Pinus ponderosa	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21821	Aeschynomene indica	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22598	Galium lovcense	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22184	Pseudocyphellaria amphisticta	Species	Lobariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22979	Hildegardia barteri	Species	Malvaceae	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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

☑ 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 NPC21573 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	297
0.1-0.2	1783
0.2-0.3	8884
0.3-0.4	9054
0.4-0.5	6243
0.5-0.6	11979
0.6-0.7	3538
0.7-0.8	599
0.8-0.85	188
0.85-0.9	96
0.9-0.95	33
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 NPC21573 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	203
0.1-0.2	773
0.2-0.3	1087
0.3-0.4	1817
0.4-0.5	2700
0.5-0.6	1797
0.6-0.7	600
0.7-0.8	159
0.8-0.85	12
0.85-0.9	2
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