NPASS Compound

Structure

NPC246597 OpenBabel06302216112D 23 26 0 0 1 0 0 0 0 0999 V2000 -4.0955 2.4127 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0953 1.4278 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2423 0.9356 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4318 1.4038 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6211 0.9360 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8108 1.4039 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0001 0.9361 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.8104 1.4041 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6210 0.0004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8107 -0.4675 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8106 -1.4037 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0003 -1.8716 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8103 -1.4037 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8104 -0.4680 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6209 0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4314 -0.4682 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2421 -0.0004 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0948 -0.4930 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9478 -0.0007 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6539 -1.8909 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0003 -2.8074 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9310 -2.9052 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 17 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 15 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 7 20 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 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 1 0 0 0 0 12 22 1 6 0 0 0 13 14 1 0 0 0 0 13 21 1 1 0 0 0 14 15 1 1 0 0 0 14 20 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 17 18 1 0 0 0 0 18 19 1 0 0 0 0 20 10 1 6 0 0 0 22 23 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	317.16
Volume:	321.27
LogP:	1.441
LogD:	1.849
LogS:	-1.545
# Rotatable Bonds:	3
TPSA:	51.16
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.86
Synthetic Accessibility Score:	4.012
Fsp3:	0.556
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.545
MDCK Permeability:	2.5593584723537788e-05
Pgp-inhibitor:	0.074
Pgp-substrate:	0.956
Human Intestinal Absorption (HIA):	0.119
20% Bioavailability (F20%):	0.729
30% Bioavailability (F30%):	0.489

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.99
Plasma Protein Binding (PPB):	63.504859924316406%
Volume Distribution (VD):	1.47
Pgp-substrate:	30.70306396484375%

ADMET: Metabolism

CYP1A2-inhibitor:	0.068
CYP1A2-substrate:	0.816
CYP2C19-inhibitor:	0.022
CYP2C19-substrate:	0.91
CYP2C9-inhibitor:	0.009
CYP2C9-substrate:	0.409
CYP2D6-inhibitor:	0.376
CYP2D6-substrate:	0.873
CYP3A4-inhibitor:	0.011
CYP3A4-substrate:	0.678

ADMET: Excretion

Clearance (CL):	13.087
Half-life (T1/2):	0.432

ADMET: Toxicity

hERG Blockers:	0.023
Human Hepatotoxicity (H-HT):	0.161
Drug-inuced Liver Injury (DILI):	0.155
AMES Toxicity:	0.102
Rat Oral Acute Toxicity:	0.919
Maximum Recommended Daily Dose:	0.898
Skin Sensitization:	0.077
Carcinogencity:	0.673
Eye Corrosion:	0.004
Eye Irritation:	0.015
Respiratory Toxicity:	0.974

Download Data

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

Natural Product: NPC246597

Natural Product ID:	NPC246597
*Common Name:**	VOIMPDXOQJYVDI-WNRNVDISSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	VOIMPDXOQJYVDI-WNRNVDISSA-N
Standard InCHI:	InChI=1S/C18H23NO4/c1-21-13-7-11-9-19-5-4-10-6-15(23-3)18(20)16(17(10)19)12(11)8-14(13)22-2/h6-8,15-18,20H,4-5,9H2,1-3H3/t15-,16-,17+,18+/m0/s1
SMILES:	COc1cc2CN3CCC4=C[C@@H]([C@H]([C@@H](c2cc1OC)[C@H]34)O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	10403528
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001253] Quinolines and derivatives [CHEMONTID:0001908] Benzoquinolines [CHEMONTID:0000100] Phenanthridines 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
NPO23000	Zephyranthes carinata	Species	Amaryllidaceae	Eukaryota	Whole Plants	n.a.	n.a.	PMID[28898076]
NPO23000	Zephyranthes carinata	Species	Amaryllidaceae	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
IC50	8

Activity Type	# Activity
Cell Line	3
Individual Protein	1
NON-MOLECULAR	3
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[20550100]
NPT916	Cell Line	SK-MEL	Homo sapiens	IC50	>	10000.0	nM	PMID[20550100]
NPT169	Cell Line	B16-F10	Mus musculus	IC50	>	10000.0	nM	PMID[20550100]
NPT204	Individual Protein	Acetylcholinesterase	Homo sapiens	IC50	=	6100.0	nM	PMID[28898076]
NPT20529	NON-MOLECULAR	NON-PROTEIN TARGET	n.a.	IC50	>	10000.0	nM	PMID[20550100]
NPT844	Organism	Trypanosoma brucei rhodesiense	Trypanosoma brucei rhodesiense	IC50	=	3.1	ug.mL-1	PMID[31515186]

☑ 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 NPC246597 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	245
0.1-0.2	1203
0.2-0.3	3995
0.3-0.4	12874
0.4-0.5	6523
0.5-0.6	12838
0.6-0.7	3948
0.7-0.8	748
0.8-0.85	208
0.85-0.9	83
0.9-0.95	25
0.95-1	7

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 NPC246597 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	161
0.1-0.2	613
0.2-0.3	890
0.3-0.4	2188
0.4-0.5	2747
0.5-0.6	1682
0.6-0.7	692
0.7-0.8	150
0.8-0.85	23
0.85-0.9	4
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