NPASS Compound

Structure

NPC473683 OpenBabel07101718232D 45 48 0 0 1 0 0 0 0 0999 V2000 -13.6652 1.0905 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -12.6550 2.2424 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 -4.3198 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6910 -3.4538 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 -5.6938 -0.3806 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 -6.1006 -1.2941 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 -9.3465 0.0490 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 -11.1261 -0.8578 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 -8.6774 -0.6942 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 -11.9921 -0.3578 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 -11.1261 1.1422 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6750 -2.0878 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -10.2601 0.6422 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 -7.6829 -0.5897 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 -10.2601 -0.3578 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8090 -0.5878 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -11.9921 0.6422 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 -12.8582 -0.8578 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 -11.1261 2.1422 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 -7.0951 -1.3987 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 -9.1774 -1.5602 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 -9.3941 1.1422 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 -7.2761 0.3239 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 -12.9581 0.3834 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -11.8616 1.6337 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3090 -3.4538 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3090 -3.4538 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -10.1556 -1.3523 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 40 1 0 0 0 0 2 41 1 0 0 0 0 3 42 1 0 0 0 0 4 43 1 0 0 0 0 5 6 1 0 0 0 0 5 7 1 0 0 0 0 6 8 1 0 0 0 0 7 9 1 0 0 0 0 8 32 1 0 0 0 0 9 33 1 0 0 0 0 10 14 1 0 0 0 0 11 15 1 0 0 0 0 12 16 2 0 0 0 0 12 24 1 0 0 0 0 13 17 2 0 0 0 0 13 25 1 0 0 0 0 14 22 1 0 0 0 0 14 34 2 0 0 0 0 15 23 1 0 0 0 0 15 35 2 0 0 0 0 16 26 1 0 0 0 0 16 28 1 0 0 0 0 17 27 1 0 0 0 0 17 29 1 0 0 0 0 18 20 1 0 0 0 0 18 26 1 0 0 0 0 18 30 1 1 0 0 0 19 21 1 0 0 0 0 19 27 1 0 0 0 0 19 31 1 1 0 0 0 20 24 1 6 0 0 0 20 36 1 0 0 0 0 21 25 1 6 0 0 0 21 37 1 0 0 0 0 22 32 1 0 0 0 0 22 38 2 0 0 0 0 23 33 1 0 0 0 0 23 39 2 0 0 0 0 24 10 1 6 0 0 0 24 44 1 0 0 0 0 25 11 1 6 0 0 0 25 45 1 0 0 0 0 26 40 1 0 0 0 0 26 41 1 0 0 0 0 27 42 1 0 0 0 0 27 43 1 0 0 0 0 34 44 1 0 0 0 0 35 45 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	891.92
Volume:	634.527
LogP:	2.901
LogD:	2.853
LogS:	-5.197
# Rotatable Bonds:	14
TPSA:	178.76
# H-Bond Aceptor:	14
# H-Bond Donor:	4
# Rings:	4
# Heavy Atoms:	18

MedChem Properties

QED Drug-Likeness Score:	0.129
Synthetic Accessibility Score:	6.349
Fsp3:	0.704
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	2
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.302
MDCK Permeability:	5.093171785119921e-05
Pgp-inhibitor:	0.996
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.948
20% Bioavailability (F20%):	0.997
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.308
Plasma Protein Binding (PPB):	87.66150665283203%
Volume Distribution (VD):	0.922
Pgp-substrate:	14.316122055053711%

ADMET: Metabolism

CYP1A2-inhibitor:	0.01
CYP1A2-substrate:	0.991
CYP2C19-inhibitor:	0.087
CYP2C19-substrate:	0.78
CYP2C9-inhibitor:	0.146
CYP2C9-substrate:	0.036
CYP2D6-inhibitor:	0.003
CYP2D6-substrate:	0.126
CYP3A4-inhibitor:	0.888
CYP3A4-substrate:	0.855

ADMET: Excretion

Clearance (CL):	1.077
Half-life (T1/2):	0.023

ADMET: Toxicity

hERG Blockers:	0.003
Human Hepatotoxicity (H-HT):	0.809
Drug-inuced Liver Injury (DILI):	0.93
AMES Toxicity:	0.956
Rat Oral Acute Toxicity:	0.983
Maximum Recommended Daily Dose:	0.006
Skin Sensitization:	0.402
Carcinogencity:	0.941
Eye Corrosion:	0.003
Eye Irritation:	0.005
Respiratory Toxicity:	0.976

Download Data

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

Natural Product: NPC473683

Natural Product ID:	NPC473683
*Common Name:**	(5S,6R,7S)-7,9-Dibromo-N-[5-[[(5S,6R,7S)-7,9-Dibromo-6-Hydroxy-8,8-Dimethoxy-1-Oxa-2-Azaspiro[4.5]Deca-2,9-Diene-3-Carbonyl]Amino]Pentyl]-6-Hydroxy-8,8-Dimethoxy-1-Oxa-2-Azaspiro[4.5]Deca-2,9-Diene-3-Carboxamide
IUPAC Name:	(5S,6R,7S)-7,9-dibromo-N-[5-[[(5S,6R,7S)-7,9-dibromo-6-hydroxy-8,8-dimethoxy-1-oxa-2-azaspiro[4.5]deca-2,9-diene-3-carbonyl]amino]pentyl]-6-hydroxy-8,8-dimethoxy-1-oxa-2-azaspiro[4.5]deca-2,9-diene-3-carboxamide
Synonyms:
Standard InCHIKey:	UVBBEALTRKXRMG-FYVXYBBASA-N
Standard InCHI:	InChI=1S/C27H36Br4N4O10/c1-40-26(41-2)16(28)12-24(20(36)18(26)30)10-14(34-44-24)22(38)32-8-6-5-7-9-33-23(39)15-11-25(45-35-15)13-17(29)27(42-3,43-4)19(31)21(25)37/h12-13,18-21,36-37H,5-11H2,1-4H3,(H,32,38)(H,33,39)/t18-,19-,20-,21-,24-,25-/m0/s1
SMILES:	COC1(C(C(C2(CC(=NO2)C(=O)NCCCCCNC(=O)C3=NOC4(C3)C=C(C(C(C4O)Br)(OC)OC)Br)C=C1Br)O)Br)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL449098
PubChem CID:	44424478
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000254] Ethers [CHEMONTID:0001656] Acetals [CHEMONTID:0004472] Ketals

*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	>	10.0	ug.mL-1	PMID[551901]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[551901]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[551901]
NPT81	Cell Line	A549	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[551901]
NPT81	Cell Line	A549	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[551901]
NPT81	Cell Line	A549	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[551901]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[551901]
NPT139	Cell Line	HT-29	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[551901]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	>	10.0	ug.mL-1	PMID[551901]

☑ 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 NPC473683 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	114
0.1-0.2	851
0.2-0.3	10434
0.3-0.4	24126
0.4-0.5	6790
0.5-0.6	357
0.6-0.7	8
0.7-0.8	3
0.8-0.85	3
0.85-0.9	9
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
0.9615	High Similarity	NPC470886
0.8615	High Similarity	NPC1702
0.8615	High Similarity	NPC158672
0.8561	High Similarity	NPC470892
0.8561	High Similarity	NPC172626
0.854	High Similarity	NPC473261
0.854	High Similarity	NPC300912
0.854	High Similarity	NPC473262
0.854	High Similarity	NPC202166
0.8421	Intermediate Similarity	NPC477220
0.8056	Intermediate Similarity	NPC130714
0.803	Intermediate Similarity	NPC66855
0.791	Intermediate Similarity	NPC313173
0.7664	Intermediate Similarity	NPC260270
0.7591	Intermediate Similarity	NPC145149
0.7552	Intermediate Similarity	NPC181086
0.7448	Intermediate Similarity	NPC81079
0.7431	Intermediate Similarity	NPC304257
0.7329	Intermediate Similarity	NPC289324
0.6409	Remote Similarity	NPC202866
0.6111	Remote Similarity	NPC259071
0.6111	Remote Similarity	NPC77435
0.6087	Remote Similarity	NPC227953
0.6077	Remote Similarity	NPC174607
0.6044	Remote Similarity	NPC147847
0.596	Remote Similarity	NPC473249
0.5912	Remote Similarity	NPC243106
0.5912	Remote Similarity	NPC315210
0.5912	Remote Similarity	NPC315848
0.5912	Remote Similarity	NPC45830
0.5906	Remote Similarity	NPC273185
0.5871	Remote Similarity	NPC314361
0.5802	Remote Similarity	NPC142761
0.5745	Remote Similarity	NPC154601
0.5694	Remote Similarity	NPC251122
0.5676	Remote Similarity	NPC121571
0.5676	Remote Similarity	NPC8093
0.566	Remote Similarity	NPC477400
0.5646	Remote Similarity	NPC472536
0.5646	Remote Similarity	NPC103391
0.564	Remote Similarity	NPC327517
0.564	Remote Similarity	NPC319334
0.564	Remote Similarity	NPC322372
0.5629	Remote Similarity	NPC315188
0.5629	Remote Similarity	NPC160688
0.5621	Remote Similarity	NPC470654
0.5621	Remote Similarity	NPC470653
0.5621	Remote Similarity	NPC470650
0.562	Remote Similarity	NPC121857
0.5616	Remote Similarity	NPC314550
0.5616	Remote Similarity	NPC478024
0.5614	Remote Similarity	NPC477398
0.5608	Remote Similarity	NPC7905
0.5608	Remote Similarity	NPC315652
0.5603	Remote Similarity	NPC68001
0.5603	Remote Similarity	NPC474827
0.5603	Remote Similarity	NPC199831
0.5603	Remote Similarity	NPC474828
0.56	Remote Similarity	NPC477515
0.56	Remote Similarity	NPC67917
0.56	Remote Similarity	NPC314268
0.56	Remote Similarity	NPC313802

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 NPC473683 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	88
0.1-0.2	543
0.2-0.3	3658
0.3-0.4	4205
0.4-0.5	613
0.5-0.6	43
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
0.6014	Remote Similarity	NPD7623	Phase 3
0.6014	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.596	Remote Similarity	NPD7747	Phase 1
0.596	Remote Similarity	NPD7746	Phase 1
0.5752	Remote Similarity	NPD8074	Phase 3
0.5733	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5667	Remote Similarity	NPD7299	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