NPASS Compound

Structure

NPC289324 OpenBabel07101719242D 25 27 0 0 1 0 0 0 0 0999 V2000 -4.3962 -1.6711 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4826 -2.0779 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0878 0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1563 -1.9499 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2052 -2.2589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0878 0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -1.3090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0878 -1.6750 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5878 -0.8090 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0878 -1.6750 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7601 -1.8968 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1563 -3.5679 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5878 -0.8090 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.5878 0.9230 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.5878 -2.5411 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -6.4653 -4.5190 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.6736 -1.4901 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.7440 -2.7589 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.2052 -3.2589 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.9511 -0.3090 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.5878 -0.8090 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5878 -2.5411 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6555 -2.8913 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 1 6 1 0 0 0 0 2 18 1 0 0 0 0 3 7 2 0 0 0 0 4 8 1 0 0 0 0 4 14 1 0 0 0 0 5 6 2 0 0 0 0 5 19 1 0 0 0 0 6 20 1 0 0 0 0 7 10 1 0 0 0 0 7 15 1 0 0 0 0 8 12 1 0 0 0 0 8 21 2 0 0 0 0 9 10 1 0 0 0 0 9 11 1 0 0 0 0 9 16 1 1 0 0 0 10 22 2 0 0 0 0 11 14 1 6 0 0 0 11 23 1 0 0 0 0 12 18 1 0 0 0 0 12 24 2 0 0 0 0 13 17 2 0 0 0 0 13 19 1 0 0 0 0 13 20 1 0 0 0 0 14 3 1 6 0 0 0 14 25 1 0 0 0 0 21 25 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	474.95
Volume:	337.924
LogP:	0.14
LogD:	0.225
LogS:	-2.598
# Rotatable Bonds:	5
TPSA:	143.42
# H-Bond Aceptor:	9
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.389
Synthetic Accessibility Score:	5.258
Fsp3:	0.429
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.575
MDCK Permeability:	5.17774788022507e-05
Pgp-inhibitor:	0.193
Pgp-substrate:	0.015
Human Intestinal Absorption (HIA):	0.939
20% Bioavailability (F20%):	0.98
30% Bioavailability (F30%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.654
Plasma Protein Binding (PPB):	81.1750717163086%
Volume Distribution (VD):	0.559
Pgp-substrate:	33.829383850097656%

ADMET: Metabolism

CYP1A2-inhibitor:	0.02
CYP1A2-substrate:	0.811
CYP2C19-inhibitor:	0.373
CYP2C19-substrate:	0.04
CYP2C9-inhibitor:	0.063
CYP2C9-substrate:	0.025
CYP2D6-inhibitor:	0.038
CYP2D6-substrate:	0.064
CYP3A4-inhibitor:	0.367
CYP3A4-substrate:	0.254

ADMET: Excretion

Clearance (CL):	1.016
Half-life (T1/2):	0.767

ADMET: Toxicity

hERG Blockers:	0.24
Human Hepatotoxicity (H-HT):	0.993
Drug-inuced Liver Injury (DILI):	0.864
AMES Toxicity:	0.979
Rat Oral Acute Toxicity:	0.557
Maximum Recommended Daily Dose:	0.887
Skin Sensitization:	0.857
Carcinogencity:	0.859
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.95

Download Data

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

Natural Product: NPC289324

Natural Product ID:	NPC289324
*Common Name:**	Ceratinadin C
IUPAC Name:	(5S,6R,7S)-N-[2-(2-amino-1H-imidazol-5-yl)ethyl]-7,9-dibromo-6-hydroxy-8-oxo-1-oxa-2-azaspiro[4.5]deca-2,9-diene-3-carboxamide
Synonyms:	Ceratinadin C
Standard InCHIKey:	LDLQYSHMABUOFS-OLUVUFQESA-N
Standard InCHI:	InChI=1S/C14H15Br2N5O4/c15-7-3-14(11(23)9(16)10(7)22)4-8(21-25-14)12(24)18-2-1-6-5-19-13(17)20-6/h3,5,9,11,23H,1-2,4H2,(H,18,24)(H3,17,19,20)/t9-,11+,14-/m1/s1
SMILES:	C(CNC(=O)C1=NO[C@]2(C=C(C(=O)[C@H]([C@@H]2O)Br)Br)C1)c1c[nH]c(=N)[nH]1
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL1210514
PubChem CID:	49863117
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0001831] Carbonyl compounds [CHEMONTID:0000118] Ketones [CHEMONTID:0003487] Cyclic ketones [CHEMONTID:0004325] Cyclohexenones

*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
NPO32681	pseudoceratina sp.	Species	Pseudoceratinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18393464]
NPO32681	pseudoceratina sp.	Species	Pseudoceratinidae	Eukaryota	n.a.	Okinawan	n.a.	PMID[20584605]
NPO32681	pseudoceratina sp.	Species	Pseudoceratinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[24964362]

☑ 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
MIC	2

Activity Type	# Activity
Organism	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	MIC	>	32.0	ug.mL-1	PMID[486165]
NPT85	Organism	Filobasidiella neoformans	Cryptococcus neoformans	MIC	>	32.0	ug.mL-1	PMID[486165]

☑ 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 NPC289324 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	282
0.1-0.2	3820
0.2-0.3	28400
0.3-0.4	6791
0.4-0.5	2863
0.5-0.6	487
0.6-0.7	47
0.7-0.8	2
0.8-0.85	1
0.85-0.9	3
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.8507	High Similarity	NPC470892
0.8507	High Similarity	NPC172626
0.8406	Intermediate Similarity	NPC304257
0.8273	Intermediate Similarity	NPC181086
0.8156	Intermediate Similarity	NPC81079
0.7972	Intermediate Similarity	NPC202166
0.7972	Intermediate Similarity	NPC300912
0.7972	Intermediate Similarity	NPC473262
0.7972	Intermediate Similarity	NPC473261
0.7681	Intermediate Similarity	NPC145149
0.7626	Intermediate Similarity	NPC260270
0.7417	Intermediate Similarity	NPC130714
0.7329	Intermediate Similarity	NPC473683
0.7133	Intermediate Similarity	NPC1702
0.7133	Intermediate Similarity	NPC158672
0.7132	Intermediate Similarity	NPC243106
0.7132	Intermediate Similarity	NPC45830
0.7086	Intermediate Similarity	NPC470886
0.6986	Remote Similarity	NPC477220
0.6875	Remote Similarity	NPC313173
0.6853	Remote Similarity	NPC66855
0.6196	Remote Similarity	NPC201900
0.5833	Remote Similarity	NPC133729
0.5646	Remote Similarity	NPC147238
0.5602	Remote Similarity	NPC142761

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 NPC289324 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	636
0.2-0.3	2855
0.3-0.4	3021
0.4-0.5	2103
0.5-0.6	351
0.6-0.7	23
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
		NPD

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