NPASS Compound

Structure

CID1702 OpenBabel06191715322D 40 43 0 0 1 0 0 0 0 0999 V2000 -11.1826 -6.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6750 -4.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6993 -0.2761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2926 0.6375 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6938 -0.3806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2981 0.7420 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5845 -4.5147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0570 -1.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.4800 -2.5201 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6180 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4505 -5.0147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0570 -2.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.5018 -2.3122 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3090 0.9511 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3166 -3.5147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6750 -2.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -10.3166 -4.5147 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 -2.5878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -9.4505 -3.0147 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6750 -1.0878 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.0951 -1.3987 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8968 1.7601 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.5845 -3.5147 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8090 -0.5878 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -9.4505 -6.0147 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 0.9230 -2.5878 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -11.1826 -3.0147 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -2.5411 -2.5878 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -6.1006 -1.2941 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.8913 1.6555 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.0018 -3.1782 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 0.9511 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -9.4505 -2.0147 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5411 -0.5878 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6829 -0.5897 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4901 2.6736 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.1826 -5.0147 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 -3.5878 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.6710 -3.9214 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 37 1 0 0 0 0 2 38 1 0 0 0 0 3 4 1 0 0 0 0 3 5 1 0 0 0 0 4 6 1 0 0 0 0 5 29 1 0 0 0 0 6 30 1 0 0 0 0 7 11 2 0 0 0 0 8 12 2 0 0 0 0 9 13 1 0 0 0 0 9 23 1 0 0 0 0 10 14 1 0 0 0 0 10 24 1 0 0 0 0 11 17 1 0 0 0 0 11 25 1 0 0 0 0 12 18 1 0 0 0 0 12 26 1 0 0 0 0 13 21 1 0 0 0 0 13 31 2 0 0 0 0 14 22 1 0 0 0 0 14 32 2 0 0 0 0 15 17 2 0 0 0 0 15 19 1 0 0 0 0 15 27 1 0 0 0 0 16 18 2 0 0 0 0 16 20 1 0 0 0 0 16 28 1 0 0 0 0 17 37 1 0 0 0 0 18 38 1 0 0 0 0 19 23 1 6 0 0 0 19 33 1 0 0 0 0 20 24 1 6 0 0 0 20 34 1 0 0 0 0 21 29 1 0 0 0 0 21 35 2 0 0 0 0 22 30 1 0 0 0 0 22 36 2 0 0 0 0 23 7 1 6 0 0 0 23 39 1 0 0 0 0 24 8 1 6 0 0 0 24 40 1 0 0 0 0 31 39 1 0 0 0 0 32 40 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	813.85
Volume:	559.786
LogP:	2.427
LogD:	1.17
LogS:	-4.48
# Rotatable Bonds:	11
TPSA:	160.3
# H-Bond Aceptor:	12
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	16

MedChem Properties

QED Drug-Likeness Score:	0.259
Synthetic Accessibility Score:	5.696
Fsp3:	0.5
Lipinski Rule-of-5:	Rejected
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:	-5.352
MDCK Permeability:	3.271505192969926e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.002
Human Intestinal Absorption (HIA):	0.927
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.28
Plasma Protein Binding (PPB):	97.0933609008789%
Volume Distribution (VD):	1.25
Pgp-substrate:	4.263124942779541%

ADMET: Metabolism

CYP1A2-inhibitor:	0.193
CYP1A2-substrate:	0.538
CYP2C19-inhibitor:	0.879
CYP2C19-substrate:	0.686
CYP2C9-inhibitor:	0.758
CYP2C9-substrate:	0.04
CYP2D6-inhibitor:	0.174
CYP2D6-substrate:	0.148
CYP3A4-inhibitor:	0.951
CYP3A4-substrate:	0.287

ADMET: Excretion

Clearance (CL):	1.11
Half-life (T1/2):	0.059

ADMET: Toxicity

hERG Blockers:	0.106
Human Hepatotoxicity (H-HT):	0.968
Drug-inuced Liver Injury (DILI):	0.9
AMES Toxicity:	0.958
Rat Oral Acute Toxicity:	0.988
Maximum Recommended Daily Dose:	0.497
Skin Sensitization:	0.925
Carcinogencity:	0.948
Eye Corrosion:	0.003
Eye Irritation:	0.007
Respiratory Toxicity:	0.979

Download Data

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

Natural Product: NPC1702

Natural Product ID:	NPC1702
*Common Name:**	Aerothionin
IUPAC Name:	(5S,6R)-7,9-dibromo-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]-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms:	(+)-Aerothionin; Aerothionin
Standard InCHIKey:	BJWQSQOWGBUSFC-UWXQAFAOSA-N
Standard InCHI:	InChI=1S/C24H26Br4N4O8/c1-37-17-11(25)7-23(19(33)15(17)27)9-13(31-39-23)21(35)29-5-3-4-6-30-22(36)14-10-24(40-32-14)8-12(26)18(38-2)16(28)20(24)34/h7-8,19-20,33-34H,3-6,9-10H2,1-2H3,(H,29,35)(H,30,36)/t19-,20-,23+,24+/m0/s1
SMILES:	COC1=C([C@@H]([C@@]2(C=C1Br)CC(=NO2)C(=O)NCCCCNC(=O)C1=NO[C@]2(C=C(C(=C([C@@H]2O)Br)OC)Br)C1)O)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL228076
PubChem CID:	10919908
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
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10096858]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[10543904]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11277747]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11720523]
NPO287	Wrightia javanica	Species	Apocynaceae	Eukaryota	n.a.	leaf	n.a.	PMID[12808258]
NPO22992	Himerometra magnipinna	Species	Himerometridae	Eukaryota	n.a.	n.a.	n.a.	PMID[17428090]
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17512741]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	red sea	n.a.	PMID[18656986]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	PMID[21542602]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[21542602]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9599257]
NPO9047.1	Brassica rapa subsp. oleifera	Subspecies	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO287	Wrightia javanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5510	Lepidium draba	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5510	Lepidium draba	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO9047.1	Brassica rapa subsp. oleifera	Subspecies	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO29034	Suberea mollis	Species	Aplysinellidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8123	Aplysina cavernicola	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2651	Ceroplastes floridensis	Species	Coccidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4817	Briareum excavatum	Species	Briareidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3266	Euryops sulcatus	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22992	Himerometra magnipinna	Species	Himerometridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO287	Wrightia javanica	Species	Apocynaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1594	[enterobacter] aerogenes	Species	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO1512	Cissampelos fasciculata	Species	Menispermaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9047.1	Brassica rapa subsp. oleifera	Subspecies	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27875	Fallopia convolvulus	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7223	Castela tortuosa	Species	Simaroubaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6901	Lophosoria quadripinnata	Species	Dicksoniaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5510	Lepidium draba	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8290	Mycena megaspora	Species	Tricholomataceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3434	Thymus camphoratus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6725	Tulipa hybrid	Species	Liliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4191	Thermococcus acidaminovorans	Species	Thermococcaceae	Archaea	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
EC50	1
GI50	3
Others	10

Activity Type	# Activity
Cell Line	10
CELL-LINE	1
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[453207]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[453207]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[453207]
NPT81	Cell Line	A549	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[453207]
NPT81	Cell Line	A549	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[453207]
NPT81	Cell Line	A549	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[453207]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[453207]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[453207]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[453207]
NPT165	Cell Line	HeLa	Homo sapiens	EC50	=	42000.0	nM	PMID[453211]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	5.0	mm	PMID[453209]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	IZ	=	3.0	mm	PMID[453209]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	IZ	=	5.0	mm	PMID[453210]
NPT20972	CELL-LINE	SU.86.86	Homo sapiens	Activity	>	20.0	%	PMID[453212]

☑ 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 NPC1702 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	116
0.1-0.2	906
0.2-0.3	14321
0.3-0.4	24089
0.4-0.5	3060
0.5-0.6	168
0.6-0.7	20
0.7-0.8	0
0.8-0.85	3
0.85-0.9	5
0.9-0.95	5
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC158672
0.975	High Similarity	NPC477220
0.907	High Similarity	NPC473262
0.907	High Similarity	NPC202166
0.907	High Similarity	NPC300912
0.907	High Similarity	NPC473261
0.9008	High Similarity	NPC66855
0.9	High Similarity	NPC470886
0.8871	High Similarity	NPC260270
0.8862	High Similarity	NPC313173
0.879	High Similarity	NPC145149
0.8692	High Similarity	NPC181086
0.8615	High Similarity	NPC473683
0.8561	High Similarity	NPC81079
0.855	High Similarity	NPC304257
0.8529	High Similarity	NPC130714
0.8372	Intermediate Similarity	NPC172626
0.8372	Intermediate Similarity	NPC470892
0.7133	Intermediate Similarity	NPC289324
0.6802	Remote Similarity	NPC202866
0.6491	Remote Similarity	NPC259071
0.6491	Remote Similarity	NPC77435
0.6453	Remote Similarity	NPC174607
0.6416	Remote Similarity	NPC147847
0.6279	Remote Similarity	NPC45830
0.6279	Remote Similarity	NPC243106
0.6271	Remote Similarity	NPC227953
0.6215	Remote Similarity	NPC201900
0.5909	Remote Similarity	NPC315848
0.5909	Remote Similarity	NPC315210
0.585	Remote Similarity	NPC475610
0.5827	Remote Similarity	NPC314550
0.5822	Remote Similarity	NPC36254
0.5821	Remote Similarity	NPC474828
0.5821	Remote Similarity	NPC68001
0.5821	Remote Similarity	NPC474827
0.5821	Remote Similarity	NPC199831
0.5754	Remote Similarity	NPC121571
0.5754	Remote Similarity	NPC8093
0.5743	Remote Similarity	NPC473249
0.5683	Remote Similarity	NPC251122
0.5682	Remote Similarity	NPC52820
0.5672	Remote Similarity	NPC313234
0.5652	Remote Similarity	NPC474099
0.5652	Remote Similarity	NPC471338
0.5652	Remote Similarity	NPC474678
0.5622	Remote Similarity	NPC475843
0.5612	Remote Similarity	NPC298484

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 NPC1702 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	86
0.1-0.2	435
0.2-0.3	3642
0.3-0.4	4515
0.4-0.5	460
0.5-0.6	12
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
0.5793	Remote Similarity	NPD7623	Phase 3
0.5793	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5743	Remote Similarity	NPD7746	Phase 1
0.5743	Remote Similarity	NPD7747	Phase 1
0.5649	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