NPASS Compound

Structure

NPC130714 OpenBabel07101718292D 39 43 0 0 1 0 0 0 0 0999 V2000 2.6366 -3.1887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5594 2.8363 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5540 2.9408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1527 1.9228 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1417 2.1318 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1582 1.8182 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 0.9067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2346 -1.6887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3392 0.3059 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 -2.6456 0.4067 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3686 -2.1887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3173 0.5138 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 3.5026 -0.6887 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 3.5026 -1.6887 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7796 -1.0933 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.3686 -0.1887 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.9135 -0.5933 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 6.7240 1.4273 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 5.2346 -0.6887 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 -3.5116 0.9067 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 4.3686 -3.1887 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.6366 -0.1887 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 6.1363 2.2363 0.0000 N 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 6.8173 -0.3522 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 -3.5116 -1.0933 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.3686 0.8113 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7186 1.5319 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 2.6366 -2.1887 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9135 -1.5933 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 36 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 28 1 0 0 0 0 6 29 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 16 1 0 0 0 0 11 25 1 0 0 0 0 12 17 1 0 0 0 0 12 26 1 0 0 0 0 13 21 1 0 0 0 0 13 30 2 0 0 0 0 14 22 1 0 0 0 0 14 31 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 32 2 0 0 0 0 17 36 1 0 0 0 0 18 16 1 1 0 0 0 18 20 1 0 0 0 0 18 37 1 0 0 0 0 19 23 1 6 0 0 0 19 33 1 0 0 0 0 20 24 1 1 0 0 0 20 37 1 0 0 0 0 21 28 1 0 0 0 0 21 34 2 0 0 0 0 22 29 1 0 0 0 0 22 35 2 0 0 0 0 23 8 1 6 0 0 0 23 38 1 0 0 0 0 24 7 1 6 0 0 0 24 39 1 0 0 0 0 30 38 1 0 0 0 0 31 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	733.92
Volume:	531.946
LogP:	2.228
LogD:	1.064
LogS:	-4.562
# Rotatable Bonds:	11
TPSA:	160.44
# H-Bond Aceptor:	12
# H-Bond Donor:	3
# Rings:	5
# Heavy Atoms:	15

MedChem Properties

QED Drug-Likeness Score:	0.239
Synthetic Accessibility Score:	5.77
Fsp3:	0.542
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.291
MDCK Permeability:	2.584601315902546e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.875
20% Bioavailability (F20%):	1.0
30% Bioavailability (F30%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.17
Plasma Protein Binding (PPB):	94.62198638916016%
Volume Distribution (VD):	1.143
Pgp-substrate:	6.254456043243408%

ADMET: Metabolism

CYP1A2-inhibitor:	0.038
CYP1A2-substrate:	0.562
CYP2C19-inhibitor:	0.793
CYP2C19-substrate:	0.554
CYP2C9-inhibitor:	0.432
CYP2C9-substrate:	0.023
CYP2D6-inhibitor:	0.025
CYP2D6-substrate:	0.133
CYP3A4-inhibitor:	0.945
CYP3A4-substrate:	0.222

ADMET: Excretion

Clearance (CL):	0.814
Half-life (T1/2):	0.046

ADMET: Toxicity

hERG Blockers:	0.081
Human Hepatotoxicity (H-HT):	0.835
Drug-inuced Liver Injury (DILI):	0.88
AMES Toxicity:	0.981
Rat Oral Acute Toxicity:	0.945
Maximum Recommended Daily Dose:	0.659
Skin Sensitization:	0.877
Carcinogencity:	0.927
Eye Corrosion:	0.003
Eye Irritation:	0.006
Respiratory Toxicity:	0.975

Download Data

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

Natural Product: NPC130714

Natural Product ID:	NPC130714
*Common Name:**	Aplysinone C
IUPAC Name:	(1'R,5S,6'S)-3'-bromo-N-[5-[[(5S,6R)-7,9-dibromo-6-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,7,9-triene-3-carbonyl]amino]pentyl]-2'-oxospiro[4H-1,2-oxazole-5,5'-7-oxabicyclo[4.1.0]hept-3-ene]-3-carboxamide
Synonyms:	Aplysinone C
Standard InCHIKey:	GSUVKSRKZPOPBP-DRRHGHKVSA-N
Standard InCHI:	InChI=1S/C24H25Br3N4O8/c1-36-17-12(26)8-23(19(33)15(17)27)9-13(30-38-23)21(34)28-5-3-2-4-6-29-22(35)14-10-24(39-31-14)7-11(25)16(32)18-20(24)37-18/h7-8,18-20,33H,2-6,9-10H2,1H3,(H,28,34)(H,29,35)/t18-,19-,20-,23+,24+/m0/s1
SMILES:	COC1=C(Br)[C@@H]([C@]2(C=C1Br)ON=C(C2)C(=O)NCCCCCNC(=O)C1=NO[C@@]2(C1)C=C(Br)C(=O)[C@H]1[C@@H]2O1)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL229729
PubChem CID:	44424474
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
NPT139	Cell Line	HT-29	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[568329]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	GI50	=	5600.0	nM	PMID[568329]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	TGI	=	5800.0	nM	PMID[568329]
NPT82	Cell Line	MDA-MB-231	Homo sapiens	LC50	=	6400.0	nM	PMID[568329]
NPT81	Cell Line	A549	Homo sapiens	GI50	=	10700.0	nM	PMID[568329]
NPT81	Cell Line	A549	Homo sapiens	TGI	>	10.0	ug.mL-1	PMID[568329]
NPT81	Cell Line	A549	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[568329]
NPT139	Cell Line	HT-29	Homo sapiens	GI50	=	12600.0	nM	PMID[568329]
NPT139	Cell Line	HT-29	Homo sapiens	LC50	>	10.0	ug.mL-1	PMID[568329]

☑ 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 NPC130714 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	151
0.1-0.2	1051
0.2-0.3	8301
0.3-0.4	26123
0.4-0.5	6619
0.5-0.6	425
0.6-0.7	10
0.7-0.8	4
0.8-0.85	8
0.85-0.9	0
0.9-0.95	4
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.913	High Similarity	NPC473261
0.913	High Similarity	NPC202166
0.913	High Similarity	NPC473262
0.913	High Similarity	NPC300912
0.8529	High Similarity	NPC1702
0.8529	High Similarity	NPC158672
0.8478	Intermediate Similarity	NPC172626
0.8478	Intermediate Similarity	NPC470892
0.8403	Intermediate Similarity	NPC470886
0.8345	Intermediate Similarity	NPC477220
0.8056	Intermediate Similarity	NPC473683
0.7857	Intermediate Similarity	NPC313173
0.7842	Intermediate Similarity	NPC66855
0.7746	Intermediate Similarity	NPC260270
0.7676	Intermediate Similarity	NPC145149
0.7635	Intermediate Similarity	NPC181086
0.7533	Intermediate Similarity	NPC81079
0.7517	Intermediate Similarity	NPC304257
0.7417	Intermediate Similarity	NPC289324
0.6417	Remote Similarity	NPC202866
0.6135	Remote Similarity	NPC315848
0.6135	Remote Similarity	NPC315210
0.6129	Remote Similarity	NPC259071
0.6129	Remote Similarity	NPC77435
0.6096	Remote Similarity	NPC174607
0.6065	Remote Similarity	NPC469494
0.6064	Remote Similarity	NPC147847
0.6056	Remote Similarity	NPC45830
0.6056	Remote Similarity	NPC243106
0.6014	Remote Similarity	NPC170375
0.6013	Remote Similarity	NPC473808
0.6	Remote Similarity	NPC314361
0.5987	Remote Similarity	NPC473249
0.5974	Remote Similarity	NPC315915
0.5938	Remote Similarity	NPC227953
0.5921	Remote Similarity	NPC27413
0.5921	Remote Similarity	NPC59751
0.5921	Remote Similarity	NPC271621
0.5909	Remote Similarity	NPC477140
0.5909	Remote Similarity	NPC477143
0.5882	Remote Similarity	NPC296361
0.5878	Remote Similarity	NPC133729
0.5871	Remote Similarity	NPC469515
0.5862	Remote Similarity	NPC474828
0.5862	Remote Similarity	NPC199831
0.5862	Remote Similarity	NPC68001
0.5862	Remote Similarity	NPC474827
0.586	Remote Similarity	NPC36254
0.5855	Remote Similarity	NPC315652
0.5855	Remote Similarity	NPC7905
0.5839	Remote Similarity	NPC469603
0.5838	Remote Similarity	NPC123140
0.5828	Remote Similarity	NPC5485
0.5793	Remote Similarity	NPC128501
0.5782	Remote Similarity	NPC469852
0.5772	Remote Similarity	NPC24389
0.5743	Remote Similarity	NPC251330
0.5724	Remote Similarity	NPC313234
0.5714	Remote Similarity	NPC470746
0.5714	Remote Similarity	NPC471336
0.5714	Remote Similarity	NPC476190
0.5707	Remote Similarity	NPC8093
0.5707	Remote Similarity	NPC121571
0.5705	Remote Similarity	NPC474099
0.5696	Remote Similarity	NPC280498
0.5687	Remote Similarity	NPC475610
0.5676	Remote Similarity	NPC271269
0.5669	Remote Similarity	NPC156379
0.5669	Remote Similarity	NPC475383
0.5657	Remote Similarity	NPC185404
0.5641	Remote Similarity	NPC201900
0.5612	Remote Similarity	NPC471338
0.5612	Remote Similarity	NPC474678

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 NPC130714 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	105
0.1-0.2	638
0.2-0.3	3386
0.3-0.4	4297
0.4-0.5	693
0.5-0.6	29
0.6-0.7	2
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
0.6118	Remote Similarity	NPD7299	Clinical (unspecified phase)
0.6039	Remote Similarity	NPD7623	Phase 3
0.6039	Remote Similarity	NPD7624	Clinical (unspecified phase)
0.6014	Remote Similarity	NPD7601	Clinical (unspecified phase)
0.5987	Remote Similarity	NPD7746	Phase 1
0.5987	Remote Similarity	NPD7747	Phase 1
0.5823	Remote Similarity	NPD4816	Clinical (unspecified phase)
0.5769	Remote Similarity	NPD7739	Clinical (unspecified phase)
0.5625	Remote Similarity	NPD8273	Phase 1

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