NPASS Compound

Natural Product: NPC201900

Natural Product ID	NPC201900
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Aerophobin 1
IUPAC Name	(5R,6S)-7,9-dibromo-6-hydroxy-N-[2-(1H-imidazol-5-yl)ethyl]-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms	Aerophobin 1
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL499178
PubChem CID	14484009
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002490] Azolines [CHEMONTID:0002211] Isoxazolines

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 41 43 0 0 0 0 0 0 0 0999 V2000 6.8929 -0.9668 -1.3008 C 0 0 0 0 0 0 0 0 0 0 0 0 6.1139 0.1438 -1.0749 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9122 0.2654 -0.4148 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5010 1.4652 0.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2434 1.6827 0.7223 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3941 0.4912 0.9633 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9431 -0.7628 0.4503 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0939 -0.8908 -0.1839 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6098 -2.6301 -0.7645 Br 0 0 0 0 0 0 0 0 0 0 0 0 0.9605 0.6654 0.5015 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1558 0.1409 1.6068 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9220 -0.0144 2.6130 N 0 0 0 0 0 0 0 0 0 0 0 0 2.2215 0.3437 2.3654 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2844 -0.1725 1.6182 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8458 -0.6203 2.6462 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0852 0.0216 0.4667 N 0 0 0 0 0 0 0 0 0 0 0 0 -3.4971 -0.2982 0.5172 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1776 -0.0232 -0.8072 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6136 -0.3613 -0.7151 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6296 0.4848 -0.3351 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.8146 -0.1822 -0.3714 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.5280 -1.4415 -0.7745 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1893 -1.5429 -0.9813 N 0 0 0 0 0 0 0 0 0 0 0 0 2.5232 2.7068 0.0535 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6430 2.9443 -0.3303 Br 0 0 0 0 0 0 0 0 0 0 0 0 7.9291 -0.6885 -1.6666 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4592 -1.5280 -2.1698 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0094 -1.6586 -0.4460 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5315 2.1872 1.6969 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3547 -1.6556 0.6054 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7330 1.7549 0.3175 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8191 0.1331 -0.4494 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6365 0.3962 -0.4073 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0240 0.1664 1.3604 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5478 -1.4123 0.6852 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6753 -0.4911 -1.6509 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1092 1.0819 -0.9636 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5814 1.5345 -0.0371 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2171 -2.2548 -0.9189 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7076 -2.4026 -1.2944 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1975 3.3887 -0.2577 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 6 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 11 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 5 24 1 0 4 25 1 0 8 3 1 0 23 19 1 0 6 13 1 1 1 26 1 0 1 27 1 0 1 28 1 0 5 29 1 1 7 30 1 0 10 31 1 0 10 32 1 0 16 33 1 0 17 34 1 0 17 35 1 0 18 36 1 0 18 37 1 0 20 38 1 0 22 39 1 0 23 40 1 0 24 41 1 0 M END

Standard InCHIKey	MDUQIEXQKMPARD-HIFRSBDPSA-N
Standard InCHI	InChI=1S/C15H16Br2N4O4/c1-24-12-9(16)4-15(13(22)11(12)17)5-10(21-25-15)14(23)19-3-2-8-6-18-7-20-8/h4,6-7,13,22H,2-3,5H2,1H3,(H,18,20)(H,19,23)/t13-,15+/m1/s1
SMILES	COC1=C([C@H]([C@]2(C=C1Br)CC(=NO2)C(=O)NCCc1cnc[nH]1)O)Br

Calculated Properties

Physi-Chem Properties

MedChem Properties

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

ADMET: Distribution

ADMET: Metabolism

ADMET: Excretion

ADMET: Toxicity

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]
NPO13261	Suberea clavata	Species	Aplysinellidae	Eukaryota	n.a.	Australian	n.a.	PMID[19379003]
NPO13261	Suberea clavata	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13261	Suberea clavata	Species	Aplysinellidae	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	Organism Name	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
Inhibition	2
ID50	2

Activity Type	# Activity
Individual protein	2
Cell line	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4197	Individual protein	Coagulation factor XI	Homo sapiens	Inhibition	=	59.0	%	PMID[18053715]
NPT4655	Individual protein	Coagulation factor IX	Homo sapiens	Inhibition	<	5.0	%	PMID[18053715]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT179	Cell line	A2780	Homo sapiens	ID50	=	21.53	ug ml-1	PMID[23398362]
NPT111	Cell line	K562	Homo sapiens	ID50	=	24.11	ug ml-1	PubChem BioAssay data set

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC201900 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	25036
0.1-0.2	24694
0.2-0.3	74
0.3-0.4	4
0.4-0.5	17
0.5-0.6	23
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8108	Intermediate Similarity	NPC608121
0.7105	Intermediate Similarity	NPC600759
0.6974	Remote Similarity	NPC304257
0.6197	Remote Similarity	NPC1702
0.6027	Remote Similarity	NPC158672
0.5976	Remote Similarity	NPC181086
0.5926	Remote Similarity	NPC81079
0.5859	Remote Similarity	NPC603907
0.5854	Remote Similarity	NPC487872
0.5854	Remote Similarity	NPC608122
0.5789	Remote Similarity	NPC487917
0.573	Remote Similarity	NPC601097
0.5647	Remote Similarity	NPC487873
0.5444	Remote Similarity	NPC202866
0.5441	Remote Similarity	NPC30521
0.5432	Remote Similarity	NPC473262
0.5432	Remote Similarity	NPC202166
0.5301	Remote Similarity	NPC145149
0.5301	Remote Similarity	NPC473261
0.5301	Remote Similarity	NPC300912
0.5238	Remote Similarity	NPC313173
0.5176	Remote Similarity	NPC260270
0.5172	Remote Similarity	NPC130714
0.5143	Remote Similarity	NPC185172
0.5116	Remote Similarity	NPC470886
0.5104	Remote Similarity	NPC147847
0.5057	Remote Similarity	NPC66855
0.5053	Remote Similarity	NPC603425

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC201900 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4880
0.1-0.2	4230
0.2-0.3	40
0.3-0.4	0
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
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

Similarity level is defined by 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