NPASS Compound

Structure

NPC181086 OpenBabel07101719522D 27 29 0 0 1 0 0 0 0 0999 V2000 4.0878 0.0570 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3962 -1.6711 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 -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 -6.3267 -0.8740 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1187 -1.8522 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 0 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 -7.7279 -1.6830 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 -8.7061 -1.8909 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 -7.3212 -0.7695 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.9848 -2.3522 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 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 3.5878 -0.8090 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 26 1 0 0 0 0 2 3 1 0 0 0 0 2 4 1 0 0 0 0 3 8 1 0 0 0 0 4 20 1 0 0 0 0 5 9 2 0 0 0 0 6 10 1 0 0 0 0 6 16 1 0 0 0 0 7 8 2 0 0 0 0 7 21 1 0 0 0 0 8 22 1 0 0 0 0 9 12 1 0 0 0 0 9 17 1 0 0 0 0 10 14 1 0 0 0 0 10 23 2 0 0 0 0 11 12 2 0 0 0 0 11 13 1 0 0 0 0 11 18 1 0 0 0 0 12 26 1 0 0 0 0 13 16 1 6 0 0 0 13 24 1 0 0 0 0 14 20 1 0 0 0 0 14 25 2 0 0 0 0 15 19 2 0 0 0 0 15 21 1 0 0 0 0 15 22 1 0 0 0 0 16 5 1 6 0 0 0 16 27 1 0 0 0 0 23 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	502.98
Volume:	372.516
LogP:	1.181
LogD:	0.952
LogS:	-3.021
# Rotatable Bonds:	7
TPSA:	135.58
# H-Bond Aceptor:	9
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.373
Synthetic Accessibility Score:	5.004
Fsp3:	0.438
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.538
MDCK Permeability:	4.241636270307936e-05
Pgp-inhibitor:	0.9
Pgp-substrate:	0.014
Human Intestinal Absorption (HIA):	0.918
20% Bioavailability (F20%):	0.995
30% Bioavailability (F30%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.581
Plasma Protein Binding (PPB):	86.7668228149414%
Volume Distribution (VD):	1.003
Pgp-substrate:	25.248645782470703%

ADMET: Metabolism

CYP1A2-inhibitor:	0.093
CYP1A2-substrate:	0.864
CYP2C19-inhibitor:	0.539
CYP2C19-substrate:	0.042
CYP2C9-inhibitor:	0.102
CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.081
CYP2D6-substrate:	0.076
CYP3A4-inhibitor:	0.796
CYP3A4-substrate:	0.194

ADMET: Excretion

Clearance (CL):	1.377
Half-life (T1/2):	0.722

ADMET: Toxicity

hERG Blockers:	0.629
Human Hepatotoxicity (H-HT):	0.996
Drug-inuced Liver Injury (DILI):	0.929
AMES Toxicity:	0.905
Rat Oral Acute Toxicity:	0.945
Maximum Recommended Daily Dose:	0.901
Skin Sensitization:	0.931
Carcinogencity:	0.766
Eye Corrosion:	0.003
Eye Irritation:	0.01
Respiratory Toxicity:	0.969

Download Data

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

Natural Product: NPC181086

Natural Product ID:	NPC181086
*Common Name:**	Aerophobin 2
IUPAC Name:	(5S,6R)-N-[3-(2-amino-1H-imidazol-5-yl)propyl]-7,9-dibromo-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms:	Aerophobin 2
Standard InCHIKey:	ZSZRBAQVYFYMTR-XJKSGUPXSA-N
Standard InCHI:	InChI=1S/C16H19Br2N5O4/c1-26-12-9(17)5-16(13(24)11(12)18)6-10(23-27-16)14(25)20-4-2-3-8-7-21-15(19)22-8/h5,7,13,24H,2-4,6H2,1H3,(H,20,25)(H3,19,21,22)/t13-,16+/m0/s1
SMILES:	COC1=C(Br)[C@@H]([C@]2(C=C1Br)ON=C(C2)C(=O)NCCCc1c[nH]c(=N)[nH]1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL518701
PubChem CID:	159038
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000436] Azoles [CHEMONTID:0000078] Imidazoles [CHEMONTID:0002310] Substituted imidazoles [CHEMONTID:0001225] Aminoimidazoles

*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
NPO33394	druinella sp.	Species	n.a.	n.a.	n.a.	Fujian, China	n.a.	PMID[12502317]
NPO40305	Pseudoceratina verrucosa	Species	Pseudoceratinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[23489291]

☑ 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
Others	5

Activity Type	# Activity
Cell Line	5

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell Line	A2780	Homo sapiens	ID50	>	10.0	ug ml-1	PMID[454375]
NPT111	Cell Line	K562	Homo sapiens	ID50	=	6.91	ug ml-1	PMID[454375]
NPT1523	Cell Line	NFF	Homo sapiens	Inhibition	=	25.0	%	PMID[454376]
NPT306	Cell Line	PC-3	Homo sapiens	Inhibition	=	66.0	%	PMID[454376]
NPT165	Cell Line	HeLa	Homo sapiens	Inhibition	=	20.0	%	PMID[454376]

☑ 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 NPC181086 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	240
0.1-0.2	2939
0.2-0.3	28722
0.3-0.4	6654
0.4-0.5	3470
0.5-0.6	601
0.6-0.7	66
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	1
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
0.9844	High Similarity	NPC81079
0.9843	High Similarity	NPC304257
0.9286	High Similarity	NPC260270
0.9206	High Similarity	NPC145149
0.8692	High Similarity	NPC1702
0.8692	High Similarity	NPC158672
0.8496	Intermediate Similarity	NPC477220
0.8385	Intermediate Similarity	NPC66855
0.8273	Intermediate Similarity	NPC289324
0.8258	Intermediate Similarity	NPC313173
0.7958	Intermediate Similarity	NPC300912
0.7958	Intermediate Similarity	NPC202166
0.7958	Intermediate Similarity	NPC473261
0.7958	Intermediate Similarity	NPC473262
0.7902	Intermediate Similarity	NPC470886
0.7635	Intermediate Similarity	NPC130714
0.7552	Intermediate Similarity	NPC473683
0.7324	Intermediate Similarity	NPC172626
0.7324	Intermediate Similarity	NPC470892
0.711	Intermediate Similarity	NPC201900
0.6718	Remote Similarity	NPC45830
0.6718	Remote Similarity	NPC243106
0.6196	Remote Similarity	NPC202866
0.6077	Remote Similarity	NPC77435
0.6077	Remote Similarity	NPC259071
0.6044	Remote Similarity	NPC174607
0.6011	Remote Similarity	NPC147847
0.5882	Remote Similarity	NPC227953
0.5878	Remote Similarity	NPC471261
0.5833	Remote Similarity	NPC147238
0.5759	Remote Similarity	NPC471256
0.5723	Remote Similarity	NPC477400
0.5714	Remote Similarity	NPC475610
0.5714	Remote Similarity	NPC473249
0.5671	Remote Similarity	NPC142761
0.5622	Remote Similarity	NPC477254

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 NPC181086 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	148
0.1-0.2	589
0.2-0.3	2239
0.3-0.4	3207
0.4-0.5	2432
0.5-0.6	501
0.6-0.7	34
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
0.5762	Remote Similarity	NPD7623	Phase 3
0.5762	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5714	Remote Similarity	NPD7746	Phase 1
0.5714	Remote Similarity	NPD7747	Phase 1
0.5625	Remote Similarity	NPD8065	Phase 2

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