NPASS Compound

Structure

NPC118653 OpenBabel06302215172D 38 45 0 0 1 0 0 0 0 0999 V2000 8.4143 2.9127 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 8.4141 1.9413 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5728 1.4557 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5726 0.4843 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7313 -0.0012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8901 0.4846 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8903 1.4560 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0488 -0.0009 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.2076 0.4849 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 3.3663 -0.0007 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5247 0.4852 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6834 -0.0003 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8417 0.4856 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.0001 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0003 -0.9927 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8412 0.4859 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7657 0.1857 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.3369 0.9722 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3036 0.8708 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6991 -0.0171 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.1279 -0.8036 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1612 -0.7022 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.5568 -1.5901 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7127 -0.1234 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3116 0.7012 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8969 1.6322 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3251 0.5949 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7654 1.7585 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8410 1.4579 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.0003 1.9435 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0005 2.9362 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8419 1.4576 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5249 1.4572 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3667 1.9428 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.2078 1.4569 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2081 2.4283 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8414 0.4862 0.0000 S 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 S 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 5 1 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 6 8 1 0 0 0 0 9 8 1 1 0 0 0 9 10 1 0 0 0 0 9 35 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 13 32 1 0 0 0 0 13 38 1 6 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 14 16 1 0 0 0 0 16 29 1 0 0 0 0 16 17 1 0 0 0 0 17 18 1 6 0 0 0 17 22 1 0 0 0 0 18 19 2 0 0 0 0 18 28 1 0 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 20 24 1 1 0 0 0 21 22 1 0 0 0 0 21 23 1 1 0 0 0 22 23 1 1 0 0 0 24 25 1 0 0 0 0 25 26 2 0 0 0 0 25 27 1 0 0 0 0 28 29 1 0 0 0 0 29 30 1 0 0 0 0 29 37 1 6 0 0 0 30 31 2 0 0 0 0 30 32 1 0 0 0 0 32 33 1 0 0 0 0 33 11 1 6 0 0 0 33 34 1 0 0 0 0 34 35 1 0 0 0 0 34 36 1 1 0 0 0 35 36 1 1 0 0 0 37 38 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	560.13
Volume:	503.315
LogP:	3.501
LogD:	2.299
LogS:	-4.607
# Rotatable Bonds:	8
TPSA:	118.28
# H-Bond Aceptor:	10
# H-Bond Donor:	0
# Rings:	9
# Heavy Atoms:	12

MedChem Properties

QED Drug-Likeness Score:	0.157
Synthetic Accessibility Score:	7.279
Fsp3:	0.692
Lipinski Rule-of-5:	Accepted
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:	-5.075
MDCK Permeability:	2.870293246814981e-05
Pgp-inhibitor:	0.624
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.74
20% Bioavailability (F20%):	0.004
30% Bioavailability (F30%):	0.989

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.053
Plasma Protein Binding (PPB):	79.76959991455078%
Volume Distribution (VD):	2.022
Pgp-substrate:	24.512731552124023%

ADMET: Metabolism

CYP1A2-inhibitor:	0.02
CYP1A2-substrate:	0.045
CYP2C19-inhibitor:	0.74
CYP2C19-substrate:	0.834
CYP2C9-inhibitor:	0.934
CYP2C9-substrate:	0.032
CYP2D6-inhibitor:	0.179
CYP2D6-substrate:	0.03
CYP3A4-inhibitor:	0.851
CYP3A4-substrate:	0.965

ADMET: Excretion

Clearance (CL):	11.69
Half-life (T1/2):	0.096

ADMET: Toxicity

hERG Blockers:	0.014
Human Hepatotoxicity (H-HT):	0.593
Drug-inuced Liver Injury (DILI):	0.999
AMES Toxicity:	0.015
Rat Oral Acute Toxicity:	0.952
Maximum Recommended Daily Dose:	0.094
Skin Sensitization:	0.665
Carcinogencity:	0.472
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.724

Download Data

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

Natural Product: NPC118653

Natural Product ID:	NPC118653
*Common Name:**	RKEDAZXFFYMOPX-KGXXLAPYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	RKEDAZXFFYMOPX-KGXXLAPYSA-N
Standard InCHI:	InChI=1S/C26H28N2O8S2/c1-3-4-5-6-16(30)34-15-8-13-10-26-24(32)27-17-12(7-14(33-11(2)29)19-21(17)35-19)9-25(27,37-38-26)23(31)28(26)18(13)22-20(15)36-22/h7-8,14-15,17-22H,3-6,9-10H2,1-2H3/t14-,15-,17-,18-,19-,20-,21+,22+,25+,26+/m0/s1
SMILES:	CCCCCC(=O)O[C@H]1C=C2C[C@@]34C(=O)N5[C@H]6C(=C[C@@H]([C@H]7[C@@H]6O7)OC(=O)C)C[C@]5(C(=O)N3[C@@H]2[C@@H]2[C@H]1O2)SS4
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	25220878
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002389] Diazinanes [CHEMONTID:0000189] Piperazines [CHEMONTID:0001731] Dioxopiperazines [CHEMONTID:0003684] 2,5-dioxopiperazines [CHEMONTID:0001732] Thiodioxopiperazines [CHEMONTID:0001790] Epipolythiodioxopiperazines

*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
NPO8538	Spiraea cantoniensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20329740]
NPO3447	Beaumontia murtonii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[28598616]
NPO26637	Mentha aquatica	Species	Lamiaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO26637	Mentha aquatica	Species	Lamiaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO26637	Mentha aquatica	Species	Lamiaceae	Eukaryota	Shoot	n.a.	n.a.	Database[FooDB]
NPO6327	Garcinia smeathmannii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6327	Garcinia smeathmannii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO645	Gentianella austriaca	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1204	Ballota saxatilis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5341	Ocimum minimum	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1546	Parmelia scabrosa	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4028	Stapelia gigantea	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8538	Spiraea cantoniensis	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26637	Mentha aquatica	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3447	Beaumontia murtonii	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8309	Phyllospongia vermicularis	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6327	Garcinia smeathmannii	Species	Clusiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1050	Hackelia floribunda	Species	Boraginaceae	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 NPC118653 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	165
0.1-0.2	1334
0.2-0.3	14922
0.3-0.4	17750
0.4-0.5	7966
0.5-0.6	524
0.6-0.7	33
0.7-0.8	2
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

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 NPC118653 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	114
0.1-0.2	678
0.2-0.3	3524
0.3-0.4	3878
0.4-0.5	893
0.5-0.6	62
0.6-0.7	0
0.7-0.8	1
0.8-0.85	0
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