NPASS Compound

Structure

NPC487977 OpenBabel06302215262D 26 29 0 0 1 0 0 0 0 0999 V2000 0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 2 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 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2321 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2321 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2321 0.8660 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7321 1.7321 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7321 1.7321 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 -0.8660 1.5000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 2.0000 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 1.7969 1.8653 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0917 2.8209 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5283 3.6472 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5311 3.7219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1490 2.9888 0.0000 O 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 1.7321 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.7321 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2 1 1 6 0 0 0 2 3 1 0 0 0 0 2 24 1 0 0 0 0 3 4 2 0 0 0 0 3 26 1 0 0 0 0 4 5 1 0 0 0 0 5 6 1 0 0 0 0 5 13 1 0 0 0 0 5 25 1 1 0 0 0 6 7 1 0 0 0 0 7 12 2 0 0 0 0 7 8 1 0 0 0 0 8 9 2 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 13 24 1 0 0 0 0 13 14 2 0 0 0 0 14 15 1 0 0 0 0 15 21 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 16 22 1 0 0 0 0 17 18 2 0 0 0 0 18 19 1 0 0 0 0 19 20 2 0 0 0 0 20 21 1 0 0 0 0 22 23 2 0 0 0 0 22 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	351.12
Volume:	347.377
LogP:	1.947
LogD:	1.853
LogS:	-2.959
# Rotatable Bonds:	2
TPSA:	93.45
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.849
Synthetic Accessibility Score:	4.238
Fsp3:	0.211
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:	-4.733
MDCK Permeability:	2.98191935144132e-05
Pgp-inhibitor:	0.004
Pgp-substrate:	0.01
Human Intestinal Absorption (HIA):	0.008
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.835
Plasma Protein Binding (PPB):	93.69380187988281%
Volume Distribution (VD):	1.773
Pgp-substrate:	6.478789329528809%

ADMET: Metabolism

CYP1A2-inhibitor:	0.317
CYP1A2-substrate:	0.112
CYP2C19-inhibitor:	0.425
CYP2C19-substrate:	0.631
CYP2C9-inhibitor:	0.646
CYP2C9-substrate:	0.274
CYP2D6-inhibitor:	0.047
CYP2D6-substrate:	0.165
CYP3A4-inhibitor:	0.712
CYP3A4-substrate:	0.858

ADMET: Excretion

Clearance (CL):	7.114
Half-life (T1/2):	0.515

ADMET: Toxicity

hERG Blockers:	0.1
Human Hepatotoxicity (H-HT):	0.277
Drug-inuced Liver Injury (DILI):	0.947
AMES Toxicity:	0.174
Rat Oral Acute Toxicity:	0.83
Maximum Recommended Daily Dose:	0.979
Skin Sensitization:	0.24
Carcinogencity:	0.943
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.639

Download Data

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

Natural Product: NPC487977

Natural Product ID:	NPC487977
*Common Name:**	LTIOSJQYEGEEHY-BLVKFPJESA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	LTIOSJQYEGEEHY-BLVKFPJESA-N
Standard InCHI:	InChI=1S/C19H17N3O4/c1-12-15(23)21-19(25,11-13-7-3-2-4-8-13)18-20-16-14(17(24)22(12)18)9-5-6-10-26-16/h2-10,12,25H,11H2,1H3,(H,21,23)/t12-,19+/m1/s1
SMILES:	C[C@@H]1C(=N[C@](Cc2ccccc2)(c2nc3c(C=CC=CO3)c(=O)n12)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	44156271
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001346] Diazines [CHEMONTID:0000075] Pyrimidines and pyrimidine derivatives [CHEMONTID:0000291] Pyrimidones

*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
NPO10205	Aspergillus puniceus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31095389]
NPO10205	Aspergillus puniceus	Species	Aspergillaceae	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
EC50	1
IC50	6
Others	5

Activity Type	# Activity
Individual Protein	8
Organism	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1794	Individual Protein	LXR-alpha	Homo sapiens	FC	=	3.5	n.a.	PMID[31095389]
NPT1794	Individual Protein	LXR-alpha	Homo sapiens	EC50	=	47000.0	nM	PMID[31095389]
NPT1210	Individual Protein	T-cell protein-tyrosine phosphatase	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT205	Individual Protein	Protein-tyrosine phosphatase 1C	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT206	Individual Protein	Protein-tyrosine phosphatase 2C	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT3914	Individual Protein	Tyrosine-protein phosphatase non-receptor type 9	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT178	Individual Protein	Protein-tyrosine phosphatase 1B	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT1078	Individual Protein	Indoleamine 2,3-dioxygenase	Homo sapiens	IC50	=	14000.0	nM	PMID[31095389]
NPT3655	Organism	Cochliobolus australiensis	Cochliobolus australiensis	GI	<	50.0	%	PMID[31095389]
NPT562	Organism	Colletotrichum gloeosporioides	Colletotrichum gloeosporioides	GI	<	50.0	%	PMID[31095389]
NPT637	Organism	Fusarium oxysporum	Fusarium oxysporum	GI	<	50.0	%	PMID[31095389]
NPT826	Organism	Magnaporthe oryzae	Magnaporthe oryzae	GI	<	50.0	%	PMID[31095389]

☑ 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 NPC487977 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	312
0.1-0.2	3132
0.2-0.3	13469
0.3-0.4	11682
0.4-0.5	10775
0.5-0.6	3075
0.6-0.7	217
0.7-0.8	28
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	5

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 NPC487977 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	184
0.1-0.2	612
0.2-0.3	840
0.3-0.4	1210
0.4-0.5	3340
0.5-0.6	2445
0.6-0.7	491
0.7-0.8	28
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