NPASS Compound

Structure

NPC473261 OpenBabel07101718292D 40 43 0 0 1 0 0 0 0 0999 V2000 -3.5116 -2.0933 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5887 3.9317 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9955 3.0181 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5942 4.0362 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9900 2.9136 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0064 3.2272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0617 0.5021 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 -6.9572 2.4967 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 -7.9278 0.0021 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 -5.9790 2.7046 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 -8.7938 1.5021 0.0000 C 0 0 1 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 -8.7938 0.5021 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 -7.9278 2.0021 0.0000 C 0 0 1 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 -5.5723 3.6181 0.0000 C 0 0 0 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 -7.0617 1.5021 0.0000 C 0 0 1 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 -7.9278 -0.9979 0.0000 Br 0 0 0 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 -9.6598 2.0021 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 -4.5778 3.7226 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0119 3.3317 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.4790 1.8385 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 -9.6598 0.0021 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.9278 3.0021 0.0000 O 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 -6.1601 4.4271 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5704 2.6272 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 -6.1482 1.0954 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 38 1 0 0 0 0 2 3 1 0 0 0 0 2 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 1 0 0 0 0 15 19 1 0 0 0 0 15 27 1 6 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 33 2 0 0 0 0 18 38 1 0 0 0 0 19 23 1 6 0 0 0 19 34 1 0 0 0 0 20 24 1 6 0 0 0 20 35 1 0 0 0 0 21 29 1 0 0 0 0 21 36 2 0 0 0 0 22 30 1 0 0 0 0 22 37 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:	2.277
LogD:	0.942
LogS:	-4.524
# Rotatable Bonds:	11
TPSA:	168.14
# H-Bond Aceptor:	12
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	16

MedChem Properties

QED Drug-Likeness Score:	0.203
Synthetic Accessibility Score:	5.798
Fsp3:	0.542
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.343
MDCK Permeability:	3.1033130653668195e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.917
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.185
Plasma Protein Binding (PPB):	97.1029281616211%
Volume Distribution (VD):	0.76
Pgp-substrate:	4.921858787536621%

ADMET: Metabolism

CYP1A2-inhibitor:	0.059
CYP1A2-substrate:	0.639
CYP2C19-inhibitor:	0.81
CYP2C19-substrate:	0.65
CYP2C9-inhibitor:	0.674
CYP2C9-substrate:	0.065
CYP2D6-inhibitor:	0.021
CYP2D6-substrate:	0.138
CYP3A4-inhibitor:	0.952
CYP3A4-substrate:	0.324

ADMET: Excretion

Clearance (CL):	0.81
Half-life (T1/2):	0.053

ADMET: Toxicity

hERG Blockers:	0.085
Human Hepatotoxicity (H-HT):	0.935
Drug-inuced Liver Injury (DILI):	0.738
AMES Toxicity:	0.984
Rat Oral Acute Toxicity:	0.902
Maximum Recommended Daily Dose:	0.622
Skin Sensitization:	0.881
Carcinogencity:	0.969
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.977

Download Data

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

Natural Product: NPC473261

Natural Product ID:	NPC473261
*Common Name:**	(5S,6R)-7,9-Dibromo-N-[5-[[(5S,6R,7R)-7,9-Dibromo-6-Hydroxy-8-Oxo-1-Oxa-2-Azaspiro[4.5]Deca-2,9-Diene-3-Carbonyl]Amino]Pentyl]-6-Hydroxy-8-Methoxy-1-Oxa-2-Azaspiro[4.5]Deca-2,7,9-Triene-3-Carboxamide
IUPAC Name:	(5S,6R)-7,9-dibromo-N-[5-[[(5S,6R,7R)-7,9-dibromo-6-hydroxy-8-oxo-1-oxa-2-azaspiro[4.5]deca-2,9-diene-3-carbonyl]amino]pentyl]-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms:
Standard InCHIKey:	KCVKPVRAUSPLPZ-MMMKZMAHSA-N
Standard InCHI:	InChI=1S/C24H26Br4N4O8/c1-38-18-12(26)8-24(20(35)16(18)28)10-14(32-40-24)22(37)30-6-4-2-3-5-29-21(36)13-9-23(39-31-13)7-11(25)17(33)15(27)19(23)34/h7-8,15,19-20,34-35H,2-6,9-10H2,1H3,(H,29,36)(H,30,37)/t15-,19-,20-,23+,24+/m0/s1
SMILES:	COC1=C(C(C2(CC(=NO2)C(=O)NCCCCCNC(=O)C3=NOC4(C3)C=C(C(=O)C(C4O)Br)Br)C=C1Br)O)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL388348
PubChem CID:	44424477
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
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[17512741]
NPO8996	Aplysina gerardogreeni	Species	Aplysinidae	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
GI50	3
Others	6

Activity Type	# Activity
Cell Line	9

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	=	3500.0	nM	PMID[533183]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	=	4900.0	nM	PMID[533183]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	=	6700.0	nM	PMID[533183]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	5400.0	nM	PMID[533183]
NPT81	Cell Line	A549	Homo sapiens	TGI	=	8700.0	nM	PMID[533183]
NPT81	Cell Line	A549	Homo sapiens	LC50	=	11200.0	nM	PMID[533183]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	4800.0	nM	PMID[533183]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	=	5000.0	nM	PMID[533183]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	=	5400.0	nM	PMID[533183]

☑ 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 NPC473261 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	127
0.1-0.2	995
0.2-0.3	8926
0.3-0.4	27097
0.4-0.5	5243
0.5-0.6	275
0.6-0.7	17
0.7-0.8	0
0.8-0.85	4
0.85-0.9	4
0.9-0.95	5
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC473262
1.0	High Similarity	NPC202166
1.0	High Similarity	NPC300912
0.9302	High Similarity	NPC172626
0.9302	High Similarity	NPC470892
0.913	High Similarity	NPC130714
0.907	High Similarity	NPC158672
0.907	High Similarity	NPC1702
0.8905	High Similarity	NPC470886
0.8864	High Similarity	NPC477220
0.854	High Similarity	NPC473683
0.8209	Intermediate Similarity	NPC313173
0.8195	Intermediate Similarity	NPC66855
0.8088	Intermediate Similarity	NPC260270
0.8015	Intermediate Similarity	NPC145149
0.7972	Intermediate Similarity	NPC289324
0.7958	Intermediate Similarity	NPC181086
0.7847	Intermediate Similarity	NPC81079
0.7832	Intermediate Similarity	NPC304257
0.663	Remote Similarity	NPC202866
0.6333	Remote Similarity	NPC77435
0.6333	Remote Similarity	NPC259071
0.6324	Remote Similarity	NPC45830
0.6324	Remote Similarity	NPC243106
0.6298	Remote Similarity	NPC174607
0.6264	Remote Similarity	NPC147847
0.6129	Remote Similarity	NPC227953
0.6014	Remote Similarity	NPC133729
0.6013	Remote Similarity	NPC473249
0.5938	Remote Similarity	NPC123140
0.5887	Remote Similarity	NPC68001
0.5887	Remote Similarity	NPC199831
0.5887	Remote Similarity	NPC474827
0.5887	Remote Similarity	NPC474828
0.5828	Remote Similarity	NPC477143
0.5828	Remote Similarity	NPC477140
0.5823	Remote Similarity	NPC314361
0.582	Remote Similarity	NPC201900
0.5808	Remote Similarity	NPC470746
0.5808	Remote Similarity	NPC471336
0.5806	Remote Similarity	NPC475610
0.5806	Remote Similarity	NPC8093
0.5806	Remote Similarity	NPC121571
0.5767	Remote Similarity	NPC315210
0.5767	Remote Similarity	NPC315848
0.5764	Remote Similarity	NPC251330
0.5753	Remote Similarity	NPC469603
0.5745	Remote Similarity	NPC313234
0.5733	Remote Similarity	NPC476190
0.5724	Remote Similarity	NPC474099
0.5707	Remote Similarity	NPC471338
0.5707	Remote Similarity	NPC474678
0.5686	Remote Similarity	NPC315915
0.5677	Remote Similarity	NPC36254
0.5677	Remote Similarity	NPC475843
0.5676	Remote Similarity	NPC314550
0.565	Remote Similarity	NPC471339
0.5629	Remote Similarity	NPC271621
0.5629	Remote Similarity	NPC59751
0.5629	Remote Similarity	NPC27413
0.5616	Remote Similarity	NPC307903
0.5616	Remote Similarity	NPC140251
0.5612	Remote Similarity	NPC471337

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 NPC473261 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	94
0.1-0.2	564
0.2-0.3	3320
0.3-0.4	4594
0.4-0.5	556
0.5-0.6	19
0.6-0.7	3
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
0.6067	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.6067	Remote Similarity	NPD7623	Phase 3
0.6013	Remote Similarity	NPD7746	Phase 1
0.6013	Remote Similarity	NPD7747	Phase 1
0.5828	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.5789	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5608	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