NPASS Compound

Structure

NPC234449 OpenBabel06302215102D 45 51 0 0 1 0 0 0 0 0999 V2000 2.2870 3.2254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2870 2.2254 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1530 1.7254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1530 0.7254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2870 0.2254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2870 -0.7746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4210 -1.2746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5550 -0.7746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5550 0.2254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4210 0.7254 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4210 1.7254 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.3387 2.3187 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0682 2.8532 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6389 3.2708 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0972 3.5265 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4981 3.5924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2135 4.0858 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9967 3.7162 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0826 3.4614 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.5929 3.1477 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9737 2.6853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1837 2.1244 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1652 2.3161 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4120 1.8432 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6259 2.2590 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7790 1.7272 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1050 2.1948 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2002 1.5256 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0214 0.9539 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4297 0.7504 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5252 0.3042 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2359 -0.0485 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7797 -0.0423 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4486 -0.4509 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9227 -0.4467 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5981 -0.0330 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1745 0.1300 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6667 0.4713 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4817 -1.3442 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0385 -2.1749 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3111 -1.2746 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3111 -2.2746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4210 -2.2746 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2870 -2.7746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 11 1 0 0 0 0 2 3 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 10 2 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 7 44 1 0 0 0 0 8 9 2 0 0 0 0 8 42 1 0 0 0 0 9 39 1 0 0 0 0 9 10 1 0 0 0 0 10 11 1 0 0 0 0 11 12 1 6 0 0 0 12 13 1 0 0 0 0 13 18 2 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 16 19 1 0 0 0 0 17 18 1 0 0 0 0 19 20 1 0 0 0 0 20 25 2 0 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 22 23 1 0 0 0 0 22 28 1 0 0 0 0 23 24 2 0 0 0 0 24 25 1 0 0 0 0 25 26 1 0 0 0 0 26 27 1 0 0 0 0 28 29 1 0 0 0 0 29 38 1 0 0 0 0 29 30 2 0 0 0 0 30 31 1 0 0 0 0 31 32 1 0 0 0 0 32 33 1 0 0 0 0 33 38 2 0 0 0 0 33 34 1 0 0 0 0 34 35 2 0 0 0 0 35 36 1 0 0 0 0 35 40 1 0 0 0 0 36 37 2 0 0 0 0 36 39 1 0 0 0 0 37 38 1 0 0 0 0 40 41 1 0 0 0 0 42 43 1 0 0 0 0 44 45 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	606.27
Volume:	629.074
LogP:	6.449
LogD:	3.947
LogS:	-7.048
# Rotatable Bonds:	4
TPSA:	70.98
# H-Bond Aceptor:	8
# H-Bond Donor:	0
# Rings:	8
# Heavy Atoms:	8

MedChem Properties

QED Drug-Likeness Score:	0.248
Synthetic Accessibility Score:	5.58
Fsp3:	0.324
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected
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:	-5.875
MDCK Permeability:	2.560221400926821e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.981
Human Intestinal Absorption (HIA):	0.004
20% Bioavailability (F20%):	0.783
30% Bioavailability (F30%):	0.896

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.083
Plasma Protein Binding (PPB):	70.73973846435547%
Volume Distribution (VD):	0.663
Pgp-substrate:	5.597571849822998%

ADMET: Metabolism

CYP1A2-inhibitor:	0.063
CYP1A2-substrate:	0.969
CYP2C19-inhibitor:	0.138
CYP2C19-substrate:	0.958
CYP2C9-inhibitor:	0.099
CYP2C9-substrate:	0.743
CYP2D6-inhibitor:	0.005
CYP2D6-substrate:	0.945
CYP3A4-inhibitor:	0.176
CYP3A4-substrate:	0.952

ADMET: Excretion

Clearance (CL):	9.683
Half-life (T1/2):	0.134

ADMET: Toxicity

hERG Blockers:	0.952
Human Hepatotoxicity (H-HT):	0.048
Drug-inuced Liver Injury (DILI):	0.863
AMES Toxicity:	0.076
Rat Oral Acute Toxicity:	0.494
Maximum Recommended Daily Dose:	0.985
Skin Sensitization:	0.655
Carcinogencity:	0.036
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.636

Download Data

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

Natural Product: NPC234449

Natural Product ID:	NPC234449
*Common Name:**	VKYYZOPCSAFKST-LJAQVGFWSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	VKYYZOPCSAFKST-LJAQVGFWSA-N
Standard InCHI:	InChI=1S/C37H38N2O6/c1-39-15-13-25-20-34(42-4)36(43-5)37-35(25)29(39)17-22-6-9-26(10-7-22)44-32-18-23(8-11-30(32)40-2)16-28-27-21-33(45-37)31(41-3)19-24(27)12-14-38-28/h6-11,18-21,29H,12-17H2,1-5H3/t29-/m0/s1
SMILES:	CN1CCc2cc(c(c3c2[C@@H]1Cc1ccc(cc1)Oc1cc(ccc1OC)CC1=NCCc2cc(c(cc12)O3)OC)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	5315989
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related 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
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21123068]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28522265]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[29641206]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[8289066]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	roots	n.a.	n.a.	PMID[8450318]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[9917283]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4824	Cocculus trilobus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4824	Cocculus trilobus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5156	Hypoestes rosea	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7389	Rhodiola atuntsuensis	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4824	Cocculus trilobus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO5156	Hypoestes rosea	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1698	Glycyrrhiza inflata	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7389	Rhodiola atuntsuensis	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO96	Rhododendron capitatum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23450	Chionographis japonica	Species	Melanthiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6730	Crossopteryx febrifuga	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24372	Artemisia palustris	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4824	Cocculus trilobus	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3849	Cyclea barbata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19931	Pyrus x nivalis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1516	Passiflora suberosa	Species	Passifloraceae	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 NPC234449 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	463
0.1-0.2	2125
0.2-0.3	11476
0.3-0.4	6312
0.4-0.5	7447
0.5-0.6	11238
0.6-0.7	2953
0.7-0.8	536
0.8-0.85	50
0.85-0.9	35
0.9-0.95	58
0.95-1	4

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 NPC234449 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	226
0.1-0.2	766
0.2-0.3	1065
0.3-0.4	1929
0.4-0.5	2780
0.5-0.6	1720
0.6-0.7	573
0.7-0.8	82
0.8-0.85	3
0.85-0.9	0
0.9-0.95	6
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