NPASS Compound

Structure

CID81079 OpenBabel06191715422D 27 29 0 0 1 0 0 0 0 0999 V2000 -3.5686 1.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6428 -0.7509 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6373 -0.6463 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0550 0.0582 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9706 0.4945 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 5.5440 1.1332 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0440 0.2672 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8366 0.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4781 0.6581 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9706 2.4945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8366 1.9945 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1045 1.9945 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.4727 0.7626 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.1267 1.4696 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1045 0.9945 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7026 0.4945 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -0.9706 3.4945 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 7.9927 1.9696 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 3.0605 -0.0464 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 6.2132 1.8764 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 7.0222 0.4751 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.9781 -0.2079 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.7615 2.4945 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8794 1.6762 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7026 2.4945 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 26 1 0 0 0 0 2 3 2 0 0 0 0 2 4 1 0 0 0 0 3 8 1 0 0 0 0 4 20 1 0 0 0 0 5 9 2 0 0 0 0 6 10 1 0 0 0 0 6 16 1 0 0 0 0 7 8 2 0 0 0 0 7 21 1 0 0 0 0 8 22 1 0 0 0 0 9 12 1 0 0 0 0 9 17 1 0 0 0 0 10 14 1 0 0 0 0 10 23 2 0 0 0 0 11 12 2 0 0 0 0 11 13 1 0 0 0 0 11 18 1 0 0 0 0 12 26 1 0 0 0 0 13 16 1 6 0 0 0 13 24 1 0 0 0 0 14 20 1 0 0 0 0 14 25 2 0 0 0 0 15 19 2 0 0 0 0 15 21 1 0 0 0 0 15 22 1 0 0 0 0 16 5 1 6 0 0 0 16 27 1 0 0 0 0 23 27 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	500.96
Volume:	369.88
LogP:	1.331
LogD:	0.872
LogS:	-2.888
# Rotatable Bonds:	6
TPSA:	135.58
# H-Bond Aceptor:	9
# H-Bond Donor:	5
# Rings:	3
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.415
Synthetic Accessibility Score:	5.291
Fsp3:	0.312
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:	-5.512
MDCK Permeability:	1.5154530046856962e-05
Pgp-inhibitor:	0.997
Pgp-substrate:	0.007
Human Intestinal Absorption (HIA):	0.952
20% Bioavailability (F20%):	0.994
30% Bioavailability (F30%):	0.999

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.923
Plasma Protein Binding (PPB):	90.25591278076172%
Volume Distribution (VD):	0.99
Pgp-substrate:	23.549192428588867%

ADMET: Metabolism

CYP1A2-inhibitor:	0.067
CYP1A2-substrate:	0.881
CYP2C19-inhibitor:	0.435
CYP2C19-substrate:	0.047
CYP2C9-inhibitor:	0.057
CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.015
CYP2D6-substrate:	0.13
CYP3A4-inhibitor:	0.573
CYP3A4-substrate:	0.164

ADMET: Excretion

Clearance (CL):	1.132
Half-life (T1/2):	0.775

ADMET: Toxicity

hERG Blockers:	0.626
Human Hepatotoxicity (H-HT):	0.997
Drug-inuced Liver Injury (DILI):	0.854
AMES Toxicity:	0.896
Rat Oral Acute Toxicity:	0.909
Maximum Recommended Daily Dose:	0.835
Skin Sensitization:	0.951
Carcinogencity:	0.883
Eye Corrosion:	0.003
Eye Irritation:	0.013
Respiratory Toxicity:	0.974

Download Data

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

Natural Product: NPC81079

Natural Product ID:	NPC81079
*Common Name:**	Aplysinamisine I
IUPAC Name:	(5S,6R)-N-[(Z)-3-(2-amino-1H-imidazol-5-yl)prop-2-enyl]-7,9-dibromo-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carboxamide
Synonyms:	Aplysinamisine I
Standard InCHIKey:	RPBHRSIJJYCYKG-PDUXPGBHSA-N
Standard InCHI:	InChI=1S/C16H17Br2N5O4/c1-26-12-9(17)5-16(13(24)11(12)18)6-10(23-27-16)14(25)20-4-2-3-8-7-21-15(19)22-8/h2-3,5,7,13,24H,4,6H2,1H3,(H,20,25)(H3,19,21,22)/b3-2-/t13-,16+/m0/s1
SMILES:	COC1=C(Br)[C@@H]([C@]2(C=C1Br)ON=C(C2)C(=O)NC/C=Cc1c[nH]c(=N)[nH]1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL517447
PubChem CID:	23427561
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000436] Azoles [CHEMONTID:0000078] Imidazoles [CHEMONTID:0002310] Substituted imidazoles [CHEMONTID:0001225] Aminoimidazoles

*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
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	Taiwanese gorgonian coral	n.a.	PMID[12088433]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	Taiwanese Gorgonian coral	n.a.	PMID[12141868]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16124781]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18290631]
NPO211	Aplysina cauliformis	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[8350091]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO211	Aplysina cauliformis	Species	Aplysinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12594	Hybanthus enneaspermus	Species	Violaceae	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
IC50	3

Activity Type	# Activity
Cell Line	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell Line	MCF7	Homo sapiens	IC50	>	50.0	ug.mL-1	PMID[468538]
NPT404	Cell Line	CCRF-CEM	Homo sapiens	IC50	>	50.0	ug.mL-1	PMID[468538]
NPT393	Cell Line	HCT-116	Homo sapiens	IC50	=	10.0	ug.mL-1	PMID[468538]

☑ 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 NPC81079 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	244
0.1-0.2	3045
0.2-0.3	28034
0.3-0.4	6730
0.4-0.5	3747
0.5-0.6	837
0.6-0.7	55
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	3
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.9844	High Similarity	NPC181086
0.969	High Similarity	NPC304257
0.9141	High Similarity	NPC260270
0.9062	High Similarity	NPC145149
0.8561	High Similarity	NPC1702
0.8561	High Similarity	NPC158672
0.837	Intermediate Similarity	NPC477220
0.8258	Intermediate Similarity	NPC66855
0.8156	Intermediate Similarity	NPC289324
0.8134	Intermediate Similarity	NPC313173
0.7847	Intermediate Similarity	NPC473262
0.7847	Intermediate Similarity	NPC473261
0.7847	Intermediate Similarity	NPC300912
0.7847	Intermediate Similarity	NPC202166
0.7793	Intermediate Similarity	NPC470886
0.7533	Intermediate Similarity	NPC130714
0.7448	Intermediate Similarity	NPC473683
0.7222	Intermediate Similarity	NPC172626
0.7222	Intermediate Similarity	NPC470892
0.7029	Intermediate Similarity	NPC201900
0.6617	Remote Similarity	NPC45830
0.6617	Remote Similarity	NPC243106
0.6129	Remote Similarity	NPC202866
0.6011	Remote Similarity	NPC77435
0.6011	Remote Similarity	NPC259071
0.5978	Remote Similarity	NPC174607
0.5946	Remote Similarity	NPC147847
0.582	Remote Similarity	NPC227953
0.58	Remote Similarity	NPC471261
0.5753	Remote Similarity	NPC147238
0.575	Remote Similarity	NPC477400
0.5742	Remote Similarity	NPC473249
0.5742	Remote Similarity	NPC475610
0.5704	Remote Similarity	NPC474828
0.5704	Remote Similarity	NPC474827
0.5704	Remote Similarity	NPC199831
0.5704	Remote Similarity	NPC68001
0.5697	Remote Similarity	NPC142761
0.5687	Remote Similarity	NPC471256
0.5657	Remote Similarity	NPC114806
0.5621	Remote Similarity	NPC245534
0.5616	Remote Similarity	NPC133729
0.5613	Remote Similarity	NPC36254
0.561	Remote Similarity	NPC315848
0.561	Remote Similarity	NPC315210
0.5608	Remote Similarity	NPC314550
0.56	Remote Similarity	NPC24617

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 NPC81079 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	150
0.1-0.2	587
0.2-0.3	1988
0.3-0.4	3176
0.4-0.5	2480
0.5-0.6	744
0.6-0.7	25
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
0.5894	Remote Similarity	NPD7623	Phase 3
0.5894	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.5742	Remote Similarity	NPD7746	Phase 1
0.5742	Remote Similarity	NPD7747	Phase 1
0.5724	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5658	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.5652	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