NPASS Compound

Structure

NPC473364 OpenBabel07101718332D 21 23 0 0 1 0 0 0 0 0999 V2000 3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3301 -0.5000 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 -0.8660 -0.5000 0.0000 C 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 4.3301 -1.5000 0.0000 C 0 0 3 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 0.8660 -1.5000 0.0000 C 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 1.7321 -2.0000 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 5.1962 -2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.4641 -2.0000 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 1.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7321 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1962 -3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0622 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5000 0.8660 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5000 0.8660 0.0000 O 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 2 0 0 0 0 1 5 1 0 0 0 0 2 6 1 0 0 0 0 3 4 1 0 0 0 0 3 13 1 0 0 0 0 4 21 1 0 0 0 0 5 7 2 0 0 0 0 5 9 1 0 0 0 0 6 12 1 0 0 0 0 6 14 1 0 0 0 0 7 10 1 0 0 0 0 7 14 1 0 0 0 0 8 10 1 0 0 0 0 8 11 2 0 0 0 0 8 13 1 0 0 0 0 9 11 1 0 0 0 0 9 15 2 0 0 0 0 10 16 2 0 0 0 0 11 21 1 0 0 0 0 12 17 2 0 0 0 0 12 18 1 0 0 0 0 19 21 2 0 0 0 0 20 21 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	310.03
Volume:	267.864
LogP:	0.944
LogD:	0.076
LogS:	-3.715
# Rotatable Bonds:	1
TPSA:	136.82
# H-Bond Aceptor:	8
# H-Bond Donor:	4
# Rings:	3
# Heavy Atoms:	9

MedChem Properties

QED Drug-Likeness Score:	0.442
Synthetic Accessibility Score:	3.327
Fsp3:	0.167
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	2
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-6.464
MDCK Permeability:	5.789771876152372e-06
Pgp-inhibitor:	0.002
Pgp-substrate:	0.407
Human Intestinal Absorption (HIA):	0.026
20% Bioavailability (F20%):	0.362
30% Bioavailability (F30%):	0.983

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.006
Plasma Protein Binding (PPB):	93.51721954345703%
Volume Distribution (VD):	0.517
Pgp-substrate:	11.257062911987305%

ADMET: Metabolism

CYP1A2-inhibitor:	0.034
CYP1A2-substrate:	0.088
CYP2C19-inhibitor:	0.022
CYP2C19-substrate:	0.051
CYP2C9-inhibitor:	0.206
CYP2C9-substrate:	0.338
CYP2D6-inhibitor:	0.01
CYP2D6-substrate:	0.121
CYP3A4-inhibitor:	0.03
CYP3A4-substrate:	0.012

ADMET: Excretion

Clearance (CL):	1.364
Half-life (T1/2):	0.831

ADMET: Toxicity

hERG Blockers:	0.011
Human Hepatotoxicity (H-HT):	0.636
Drug-inuced Liver Injury (DILI):	0.99
AMES Toxicity:	0.076
Rat Oral Acute Toxicity:	0.036
Maximum Recommended Daily Dose:	0.017
Skin Sensitization:	0.127
Carcinogencity:	0.364
Eye Corrosion:	0.003
Eye Irritation:	0.042
Respiratory Toxicity:	0.874

Download Data

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

Natural Product: NPC473364

Natural Product ID:	NPC473364
*Common Name:**	1,1,5,10-Tetraoxo-3,4,6,7-Tetrahydro-2H-Pyrido[2,3-G][1,4]Benzothiazine-7-Carboxylic Acid
IUPAC Name:	1,1,5,10-tetraoxo-3,4,6,7-tetrahydro-2H-pyrido[2,3-g][1,4]benzothiazine-7-carboxylic acid
Synonyms:
Standard InCHIKey:	RIAQIBXBZCYHMD-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C12H10N2O6S/c15-9-5-1-2-6(12(17)18)14-7(5)10(16)8-11(9)21(19,20)4-3-13-8/h1-2,6,13-14H,3-4H2,(H,17,18)
SMILES:	C1CS(=O)(=O)C2=C(N1)C(=O)C3=C(C2=O)C=CC(N3)C(=O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL403339
PubChem CID:	44445522
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001253] Quinolines and derivatives [CHEMONTID:0002552] Quinoline carboxylic acids

*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
NPO30938	Perithalia capillaris	Species	Sporochnaceae	Eukaryota	n.a.	New Zealand	n.a.	PMID[18052030]
NPO30938	Perithalia capillaris	Species	Sporochnaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[21348445]

☑ 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	2

Activity Type	# Activity
Cell Line	1
Others	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT116	Cell Line	HL-60	Homo sapiens	IC50	=	73000.0	nM	PMID[557235]
NPT2	Others	Unspecified		IC50	=	1500.0	nM	PMID[557235]

☑ 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 NPC473364 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	99
0.1-0.2	5858
0.2-0.3	30782
0.3-0.4	5543
0.4-0.5	382
0.5-0.6	29
0.6-0.7	3
0.7-0.8	0
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
0.626	Remote Similarity	NPC476158
0.6132	Remote Similarity	NPC202056
0.598	Remote Similarity	NPC28529
0.5714	Remote Similarity	NPC82239
0.568	Remote Similarity	NPC176336
0.5619	Remote Similarity	NPC157173
0.561	Remote Similarity	NPC72688

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 NPC473364 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	66
0.1-0.2	782
0.2-0.3	5668
0.3-0.4	2362
0.4-0.5	255
0.5-0.6	14
0.6-0.7	3
0.7-0.8	0
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
0.6441	Remote Similarity	NPD2090	Approved
0.6311	Remote Similarity	NPD2099	Approved
0.6198	Remote Similarity	NPD2100	Approved
0.584	Remote Similarity	NPD1604	Approved
0.584	Remote Similarity	NPD1605	Approved
0.575	Remote Similarity	NPD2147	Approved
0.5714	Remote Similarity	NPD161	Discontinued

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