NPASS Compound

Structure

NPC94123 OpenBabel06302215412D 29 30 0 0 0 0 0 0 0 0999 V2000 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 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 -0.8660 -1.5000 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 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 -2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -3.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.7942 -2.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 -4.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9282 2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 0.5000 0.0000 N 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 -0.8660 0.5000 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 0.8660 0.5000 0.0000 O 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 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 27 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 25 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 6 15 2 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 10 11 1 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 14 1 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 17 18 1 0 0 0 0 17 25 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 21 22 1 0 0 0 0 22 23 2 0 0 0 0 22 24 1 0 0 0 0 25 26 2 0 0 0 0 26 27 1 0 0 0 0 27 28 1 0 0 0 0 28 29 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	401.25
Volume:	413.466
LogP:	1.194
LogD:	-0.295
LogS:	-2.047
# Rotatable Bonds:	11
TPSA:	160.15
# H-Bond Aceptor:	9
# H-Bond Donor:	8
# Rings:	2
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.249
Synthetic Accessibility Score:	2.776
Fsp3:	0.45
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:	-5.442
MDCK Permeability:	5.567232074099593e-05
Pgp-inhibitor:	0.01
Pgp-substrate:	1.0
Human Intestinal Absorption (HIA):	0.002
20% Bioavailability (F20%):	0.001
30% Bioavailability (F30%):	0.002

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.883
Plasma Protein Binding (PPB):	55.51359176635742%
Volume Distribution (VD):	1.96
Pgp-substrate:	42.31257247924805%

ADMET: Metabolism

CYP1A2-inhibitor:	0.074
CYP1A2-substrate:	0.134
CYP2C19-inhibitor:	0.004
CYP2C19-substrate:	0.048
CYP2C9-inhibitor:	0.0
CYP2C9-substrate:	0.008
CYP2D6-inhibitor:	0.106
CYP2D6-substrate:	0.91
CYP3A4-inhibitor:	0.002
CYP3A4-substrate:	0.11

ADMET: Excretion

Clearance (CL):	5.761
Half-life (T1/2):	0.106

ADMET: Toxicity

hERG Blockers:	0.384
Human Hepatotoxicity (H-HT):	0.763
Drug-inuced Liver Injury (DILI):	0.167
AMES Toxicity:	0.04
Rat Oral Acute Toxicity:	0.519
Maximum Recommended Daily Dose:	0.917
Skin Sensitization:	0.864
Carcinogencity:	0.019
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.953

Download Data

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

Natural Product: NPC94123

Natural Product ID:	NPC94123
*Common Name:**	WKRLLRULODTOQU-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	WKRLLRULODTOQU-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C20H31N7O2/c1-28-17-10-14-13(6-3-4-8-25-19(21)22)12-27-16(7-5-9-26-20(23)24)15(14)11-18(17)29-2/h10-12H,3-9H2,1-2H3,(H4,21,22,25)(H4,23,24,26)
SMILES:	COc1cc2c(CCCCNC(=N)N)cnc(CCCNC(=N)N)c2cc1OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	10069639
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002566] Isoquinolines and derivatives

*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
NPO874	Narthecium asiaticum	Species	Nartheciaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[14980692]
NPO244	Stachyurus himalaicus	Species	Stachyuraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17851408]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	bark	n.a.	PMID[20167482]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21608987]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	stem	n.a.	PMID[27113553]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	root	n.a.	PMID[2801129]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	Fruit Juice	n.a.	n.a.	Database[FooDB]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO1384	Cucumis myriocarpus	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7026	Vismia orientalis	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4129	Veronica persica	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	Fruits	n.a.		Database[Phenol-Explorer]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1384	Cucumis myriocarpus	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO4129	Veronica persica	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7026	Vismia orientalis	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO244	Stachyurus himalaicus	Species	Stachyuraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO7026	Vismia orientalis	Species	Hypericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2213	Chavica betle	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO5599	Chrysocoma peduncularis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1249	Euphorbia sieboldiana	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO591	Penicillium meleagrinum	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7379	Clostridium butyricum	Species	Clostridiaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO244	Stachyurus himalaicus	Species	Stachyuraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2277	Angylocalyx braunii	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2348	Tripterygium regelii	Species	Celastraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7235	Brachychiton populneum	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO962	Vernonanthura pinguis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5154	Tsuga diversifolia	Species	Pinaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4000	Archidendron lucidum	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4786	Chrysotila lamellosa	Species	Isochrysidaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7897	Passiflora foetida	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4129	Veronica persica	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23104	Wedelia scaberrima	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1384	Cucumis myriocarpus	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10856	Passiflora edulis	Species	Passifloraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7098	Phebalium ambiens	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO874	Narthecium asiaticum	Species	Nartheciaceae	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 NPC94123 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	545
0.1-0.2	4372
0.2-0.3	12883
0.3-0.4	7128
0.4-0.5	12157
0.5-0.6	3915
0.6-0.7	1491
0.7-0.8	183
0.8-0.85	20
0.85-0.9	3
0.9-0.95	0
0.95-1	0

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 NPC94123 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	277
0.1-0.2	642
0.2-0.3	877
0.3-0.4	1358
0.4-0.5	2567
0.5-0.6	2455
0.6-0.7	831
0.7-0.8	138
0.8-0.85	3
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