NPASS Compound

Structure

NPC66855 OpenBabel07101718222D 28 29 0 0 1 0 0 0 0 0999 V2000 7.5822 7.6131 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5116 -2.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1754 6.6995 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9716 3.6453 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3784 4.5589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9771 3.5408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3729 4.6634 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9135 -0.5933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 1.4013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 -1.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1691 1.6092 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6456 0.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6456 -0.5933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 0.9067 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.5759 2.5227 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7742 5.6815 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9135 0.4067 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7796 -2.0933 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.5116 0.9067 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 1.5704 2.6272 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7796 5.5769 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.6691 0.7431 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 1.9067 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.0119 3.3317 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.3620 4.8724 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5116 -1.0933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1809 6.5950 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 3 1 0 0 0 0 2 26 1 0 0 0 0 3 27 1 0 0 0 0 4 5 1 0 0 0 0 4 6 1 0 0 0 0 5 7 1 0 0 0 0 6 20 1 0 0 0 0 7 21 1 0 0 0 0 8 10 2 0 0 0 0 9 11 1 0 0 0 0 9 17 1 0 0 0 0 10 13 1 0 0 0 0 10 18 1 0 0 0 0 11 15 1 0 0 0 0 11 22 2 0 0 0 0 12 13 2 0 0 0 0 12 14 1 0 0 0 0 12 19 1 0 0 0 0 13 26 1 0 0 0 0 14 17 1 6 0 0 0 14 23 1 0 0 0 0 15 20 1 0 0 0 0 15 24 2 0 0 0 0 16 21 2 3 0 0 0 16 25 1 0 0 0 0 16 27 1 0 0 0 0 17 8 1 6 0 0 0 17 28 1 0 0 0 0 22 28 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	523.0
Volume:	396.592
LogP:	2.02
LogD:	1.295
LogS:	-3.888
# Rotatable Bonds:	11
TPSA:	118.48
# H-Bond Aceptor:	9
# H-Bond Donor:	3
# Rings:	2
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.418
Synthetic Accessibility Score:	4.35
Fsp3:	0.588
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:	-5.094
MDCK Permeability:	2.5653875127318315e-05
Pgp-inhibitor:	0.966
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.417
20% Bioavailability (F20%):	0.995
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.966
Plasma Protein Binding (PPB):	85.74725341796875%
Volume Distribution (VD):	0.889
Pgp-substrate:	23.990184783935547%

ADMET: Metabolism

CYP1A2-inhibitor:	0.645
CYP1A2-substrate:	0.639
CYP2C19-inhibitor:	0.706
CYP2C19-substrate:	0.779
CYP2C9-inhibitor:	0.238
CYP2C9-substrate:	0.087
CYP2D6-inhibitor:	0.04
CYP2D6-substrate:	0.261
CYP3A4-inhibitor:	0.887
CYP3A4-substrate:	0.227

ADMET: Excretion

Clearance (CL):	1.723
Half-life (T1/2):	0.247

ADMET: Toxicity

hERG Blockers:	0.087
Human Hepatotoxicity (H-HT):	0.814
Drug-inuced Liver Injury (DILI):	0.609
AMES Toxicity:	0.981
Rat Oral Acute Toxicity:	0.967
Maximum Recommended Daily Dose:	0.216
Skin Sensitization:	0.629
Carcinogencity:	0.882
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.885

Download Data

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

Natural Product: NPC66855

Natural Product ID:	NPC66855
*Common Name:**	Subereamolline A
IUPAC Name:	ethyl N-[4-[[(5S,6R)-7,9-dibromo-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carbonyl]amino]butyl]carbamate
Synonyms:
Standard InCHIKey:	OSCSKJPZRSOZDO-WMLDXEAASA-N
Standard InCHI:	InChI=1S/C17H23Br2N3O6/c1-3-27-16(25)21-7-5-4-6-20-15(24)11-9-17(28-22-11)8-10(18)13(26-2)12(19)14(17)23/h8,14,23H,3-7,9H2,1-2H3,(H,20,24)(H,21,25)/t14-,17+/m0/s1
SMILES:	CCOC(=NCCCCNC(=O)C1=NO[C@@]2(C1)C=C(Br)C(=C([C@@H]2O)Br)OC)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL523578
PubChem CID:	25016147
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002490] Azolines [CHEMONTID:0002211] Isoxazolines

*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
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	red sea	n.a.	PMID[18656986]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[21542602]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21542602]
NPO29034	Suberea mollis	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	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	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	3.0	mm	PMID[471340]

☑ 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 NPC66855 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	109
0.1-0.2	788
0.2-0.3	12011
0.3-0.4	25295
0.4-0.5	4170
0.5-0.6	287
0.6-0.7	20
0.7-0.8	3
0.8-0.85	5
0.85-0.9	7
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9655	High Similarity	NPC313173
0.9008	High Similarity	NPC260270
0.9008	High Similarity	NPC158672
0.9008	High Similarity	NPC1702
0.8926	High Similarity	NPC145149
0.879	High Similarity	NPC477220
0.8409	Intermediate Similarity	NPC470886
0.8385	Intermediate Similarity	NPC181086
0.8258	Intermediate Similarity	NPC81079
0.8244	Intermediate Similarity	NPC304257
0.8195	Intermediate Similarity	NPC473261
0.8195	Intermediate Similarity	NPC300912
0.8195	Intermediate Similarity	NPC473262
0.8195	Intermediate Similarity	NPC202166
0.803	Intermediate Similarity	NPC473683
0.7842	Intermediate Similarity	NPC130714
0.7519	Intermediate Similarity	NPC172626
0.7519	Intermediate Similarity	NPC470892
0.6853	Remote Similarity	NPC289324
0.645	Remote Similarity	NPC259071
0.645	Remote Similarity	NPC77435
0.6412	Remote Similarity	NPC174607
0.6374	Remote Similarity	NPC147847
0.6349	Remote Similarity	NPC243106
0.6349	Remote Similarity	NPC45830
0.6322	Remote Similarity	NPC227953
0.6284	Remote Similarity	NPC315848
0.6284	Remote Similarity	NPC315210
0.6264	Remote Similarity	NPC201900
0.6193	Remote Similarity	NPC202866
0.6127	Remote Similarity	NPC473249
0.6111	Remote Similarity	NPC167380
0.5977	Remote Similarity	NPC121571
0.5977	Remote Similarity	NPC8093
0.597	Remote Similarity	NPC251122
0.5969	Remote Similarity	NPC313234
0.5918	Remote Similarity	NPC314361
0.5906	Remote Similarity	NPC121857
0.5903	Remote Similarity	NPC475610
0.5896	Remote Similarity	NPC298484
0.5882	Remote Similarity	NPC314550
0.5878	Remote Similarity	NPC199831
0.5878	Remote Similarity	NPC474827
0.5878	Remote Similarity	NPC68001
0.5878	Remote Similarity	NPC474828
0.5874	Remote Similarity	NPC36254
0.5866	Remote Similarity	NPC471338
0.5866	Remote Similarity	NPC474678
0.5833	Remote Similarity	NPC475843
0.5827	Remote Similarity	NPC59751
0.5827	Remote Similarity	NPC271621
0.5827	Remote Similarity	NPC27413
0.5778	Remote Similarity	NPC133729
0.5778	Remote Similarity	NPC24389
0.5775	Remote Similarity	NPC315915
0.5761	Remote Similarity	NPC471337
0.5746	Remote Similarity	NPC315426
0.5736	Remote Similarity	NPC52820
0.5725	Remote Similarity	NPC5485
0.5706	Remote Similarity	NPC477255
0.5704	Remote Similarity	NPC474099
0.5703	Remote Similarity	NPC469739
0.5683	Remote Similarity	NPC103391
0.5683	Remote Similarity	NPC472536
0.5674	Remote Similarity	NPC296361
0.5643	Remote Similarity	NPC7905
0.5643	Remote Similarity	NPC315652
0.5639	Remote Similarity	NPC55336
0.5625	Remote Similarity	NPC273185
0.562	Remote Similarity	NPC8161
0.562	Remote Similarity	NPC469603
0.5606	Remote Similarity	NPC175531

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 NPC66855 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	79
0.1-0.2	373
0.2-0.3	3305
0.3-0.4	4730
0.4-0.5	633
0.5-0.6	25
0.6-0.7	5
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
0.6304	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.6304	Remote Similarity	NPD7623	Phase 3
0.6127	Remote Similarity	NPD7746	Phase 1
0.6127	Remote Similarity	NPD7747	Phase 1
0.6115	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5929	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.5809	Remote Similarity	NPD7116	Clinical (unspecified phase)

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