NPASS Compound

Structure

NPC205043 OpenBabel06302216042D 21 24 0 0 0 0 0 0 0 0999 V2000 2.9213 -0.7370 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9511 -0.7370 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.3808 -1.5219 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4581 -1.2221 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.4581 -0.2519 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3808 0.0479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6807 0.9706 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6296 1.1723 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8404 1.4557 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0001 0.9702 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8408 1.4556 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8406 2.4262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0004 2.9113 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8404 2.4259 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6812 -0.0001 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5217 -0.4856 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5217 -1.4558 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6809 -1.9412 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8407 -1.4561 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8405 -0.4855 0.0000 C 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 1 2 1 0 0 0 0 2 6 1 0 0 0 0 2 3 1 0 0 0 0 3 4 2 0 0 0 0 4 5 1 0 0 0 0 5 6 2 0 0 0 0 6 7 1 0 0 0 0 7 8 2 0 0 0 0 7 9 1 0 0 0 0 9 14 2 0 0 0 0 9 10 1 0 0 0 0 10 21 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 11 15 1 0 0 0 0 12 13 2 0 0 0 0 13 14 1 0 0 0 0 15 20 2 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 18 19 2 0 0 0 0 19 20 1 0 0 0 0 20 21 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	276.1
Volume:	280.116
LogP:	2.378
LogD:	2.277
LogS:	-3.586
# Rotatable Bonds:	2
TPSA:	63.57
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	4
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.572
Synthetic Accessibility Score:	2.635
Fsp3:	0.062
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	1
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.879
MDCK Permeability:	1.5808969692443497e-05
Pgp-inhibitor:	0.005
Pgp-substrate:	0.015
Human Intestinal Absorption (HIA):	0.009
20% Bioavailability (F20%):	0.014
30% Bioavailability (F30%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.982
Plasma Protein Binding (PPB):	91.19915008544922%
Volume Distribution (VD):	1.908
Pgp-substrate:	9.60104751586914%

ADMET: Metabolism

CYP1A2-inhibitor:	0.994
CYP1A2-substrate:	0.763
CYP2C19-inhibitor:	0.743
CYP2C19-substrate:	0.068
CYP2C9-inhibitor:	0.511
CYP2C9-substrate:	0.379
CYP2D6-inhibitor:	0.793
CYP2D6-substrate:	0.249
CYP3A4-inhibitor:	0.938
CYP3A4-substrate:	0.315

ADMET: Excretion

Clearance (CL):	10.389
Half-life (T1/2):	0.719

ADMET: Toxicity

hERG Blockers:	0.067
Human Hepatotoxicity (H-HT):	0.881
Drug-inuced Liver Injury (DILI):	0.985
AMES Toxicity:	0.788
Rat Oral Acute Toxicity:	0.632
Maximum Recommended Daily Dose:	0.953
Skin Sensitization:	0.75
Carcinogencity:	0.094
Eye Corrosion:	0.003
Eye Irritation:	0.076
Respiratory Toxicity:	0.981

Download Data

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

Natural Product: NPC205043

Natural Product ID:	NPC205043
*Common Name:**	AKUVPIGMKLIECB-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	AKUVPIGMKLIECB-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C16H12N4O/c1-20-9-17-8-13(20)16(21)15-14-11(6-7-18-15)10-4-2-3-5-12(10)19-14/h2-9,19H,1H3
SMILES:	Cn1cncc1C(=O)c1c2c(ccn1)c1ccccc1[nH]2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	513481
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0001140] Harmala alkaloids

*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
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15332848]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2004-Mar	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesian	n.a.	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	collected from vertical slopes between 33 and 40 m from Knife Cape Manado, Indonesia	2002-May	PMID[16872140]
NPO33280	Acanthostrongylophora sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[28452477]

☑ 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	3
MIC	6
Others	2

Activity Type	# Activity
Cell Line	2
Individual Protein	1
Organism	6
Others	1
Protein Complex	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT111	Cell Line	K562	Homo sapiens	LC50	=	13000.0	nM	PMID[28452477]
NPT81	Cell Line	A549	Homo sapiens	LC50	=	12000.0	nM	PMID[28452477]
NPT1821	Individual Protein	Sortase	Staphylococcus aureus	IC50	>	150000.0	nM	PMID[28452477]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	>	0.1	ug.mL-1	PMID[28452477]
NPT79	Organism	Bacillus subtilis	Bacillus subtilis	MIC	=	0.05	ug.mL-1	PMID[28452477]
NPT3147	Organism	Kocuria rhizophila	Kocuria rhizophila	MIC	=	0.025	ug.mL-1	PMID[28452477]
NPT566	Organism	Salmonella typhimurium	Salmonella enterica subsp. enterica serovar Typhimurium	MIC	=	0.025	ug.mL-1	PMID[28452477]
NPT25245	ORGANISM	Proteus hauseri	Proteus hauseri	MIC	>	0.1	ug.mL-1	PMID[28452477]
NPT19	Organism	Escherichia coli	Escherichia coli	MIC	>	0.1	ug.mL-1	PMID[28452477]
NPT2890	Protein Complex	Sodium/potassium-transporting ATPase	Homo sapiens	IC50	>	150000.0	nM	PMID[28452477]
NPT2	Others	Unspecified		IC50	>	150000.0	nM	PMID[28452477]

☑ 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 NPC205043 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	748
0.1-0.2	9624
0.2-0.3	19462
0.3-0.4	7616
0.4-0.5	1730
0.5-0.6	2033
0.6-0.7	1182
0.7-0.8	266
0.8-0.85	25
0.85-0.9	7
0.9-0.95	2
0.95-1	2

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 NPC205043 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	371
0.1-0.2	796
0.2-0.3	1155
0.3-0.4	2298
0.4-0.5	1770
0.5-0.6	1624
0.6-0.7	964
0.7-0.8	158
0.8-0.85	7
0.85-0.9	5
0.9-0.95	2
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