NPASS Compound

Structure

NPC127553 OpenBabel07101719252D 32 36 0 0 1 0 0 0 0 0999 V2000 3.0120 -1.0645 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8365 3.0831 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3353 -1.2436 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4789 3.3610 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6059 -0.6939 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3044 2.6282 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6358 -1.2152 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1748 3.4372 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0781 0.4759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5261 1.6266 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0641 -0.1648 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0698 2.0366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2121 -0.0241 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0598 1.7188 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9758 -0.9820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8622 3.3050 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8822 -0.1641 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3461 3.4759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0781 1.4759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6794 1.1768 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8610 0.4516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2121 2.9759 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3461 0.4759 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.2531 1.3610 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4139 -0.5645 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4800 2.9759 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3461 1.4759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2291 0.6614 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.2121 1.9759 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.3665 0.8190 0.0000 N 0 0 3 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 3.4800 1.9759 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 3 1 0 0 0 0 1 5 1 0 0 0 0 2 4 1 0 0 0 0 2 6 1 0 0 0 0 3 7 1 0 0 0 0 4 8 1 0 0 0 0 5 11 1 0 0 0 0 6 12 1 0 0 0 0 7 15 1 0 0 0 0 8 16 1 0 0 0 0 9 13 1 0 0 0 0 9 19 1 0 0 0 0 10 14 1 0 0 0 0 10 20 1 0 0 0 0 13 23 1 0 0 0 0 14 24 1 0 0 0 0 17 21 1 0 0 0 0 17 25 1 0 0 0 0 18 22 1 0 0 0 0 18 26 1 0 0 0 0 19 29 1 0 0 0 0 20 30 1 0 0 0 0 21 30 1 0 0 0 0 22 29 1 0 0 0 0 23 11 1 1 0 0 0 23 27 1 0 0 0 0 24 12 1 6 0 0 0 24 28 1 0 0 0 0 25 15 1 1 0 0 0 25 31 1 0 0 0 0 26 16 1 6 0 0 0 26 32 1 0 0 0 0 27 29 1 6 0 0 0 27 32 1 0 0 0 0 28 30 1 6 0 0 0 28 31 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	446.39
Volume:	489.636
LogP:	7.159
LogD:	4.619
LogS:	-5.907
# Rotatable Bonds:	0
TPSA:	24.94
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	5
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.434
Synthetic Accessibility Score:	5.487
Fsp3:	1.0
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-4.939
MDCK Permeability:	8.928156603360549e-06
Pgp-inhibitor:	0.012
Pgp-substrate:	0.962
Human Intestinal Absorption (HIA):	0.01
20% Bioavailability (F20%):	0.947
30% Bioavailability (F30%):	0.01

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.042
Plasma Protein Binding (PPB):	93.67208862304688%
Volume Distribution (VD):	0.987
Pgp-substrate:	3.8329596519470215%

ADMET: Metabolism

CYP1A2-inhibitor:	0.012
CYP1A2-substrate:	0.547
CYP2C19-inhibitor:	0.053
CYP2C19-substrate:	0.933
CYP2C9-inhibitor:	0.002
CYP2C9-substrate:	0.02
CYP2D6-inhibitor:	0.989
CYP2D6-substrate:	0.876
CYP3A4-inhibitor:	0.052
CYP3A4-substrate:	0.66

ADMET: Excretion

Clearance (CL):	3.563
Half-life (T1/2):	0.071

ADMET: Toxicity

hERG Blockers:	0.942
Human Hepatotoxicity (H-HT):	0.768
Drug-inuced Liver Injury (DILI):	0.787
AMES Toxicity:	0.178
Rat Oral Acute Toxicity:	0.037
Maximum Recommended Daily Dose:	0.413
Skin Sensitization:	0.978
Carcinogencity:	0.099
Eye Corrosion:	0.054
Eye Irritation:	0.425
Respiratory Toxicity:	0.842

Download Data

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

Natural Product: NPC127553

Natural Product ID:	NPC127553
*Common Name:**	PQYOPBRFUUEHRC-NIVXRMQLSA-N
IUPAC Name:	n.a.
Synonyms:	(+)-Xestospongin A
Standard InCHIKey:	PQYOPBRFUUEHRC-NIVXRMQLSA-N
Standard InCHI:	InChI=1S/C28H50N2O2/c1-3-7-15-25-17-21-30-20-10-14-24(28(30)31-25)12-6-2-4-8-16-26-18-22-29-19-9-13-23(11-5-1)27(29)32-26/h23-28H,1-22H2/t23-,24-,25-,26-,27+,28+/m1/s1
SMILES:	C1CCC[C@@H]2CCCN3[C@H]2O[C@H](CCCCCC[C@H]2[C@@H]4O[C@H](CC1)CCN4CCC2)CC3
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL456076
PubChem CID:	9889796
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000195] Piperidines

*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
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11908959]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Caledonian	n.a.	PMID[1453184]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Thai	n.a.	PMID[14640515]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	thai	n.a.	PMID[15217287]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1710256]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	coral reef habitat at a depth of approximately 20 m from the sea bed surface, at Sangalaki, Indonesia (2 04 59 N, 118 23 41 E)	1996-MAR	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Indonesia	n.a.	PMID[20503979]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[31260310]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	Philippine	n.a.	PMID[7473578]
NPO32702	xestospongia sp.	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[7798966]

☑ 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
MIC	4

Activity Type	# Activity
Organism	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT20	Organism	Candida albicans	Candida albicans	MIC	=	100.0	ug.mL-1	PMID[546089]
NPT554	Organism	Candida glabrata	Candida glabrata	MIC	=	100.0	ug.mL-1	PMID[546089]
NPT187	Organism	Issatchenkia orientalis	Pichia kudriavzevii	MIC	=	100.0	ug.mL-1	PMID[546089]

☑ 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 NPC127553 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	152
0.1-0.2	8165
0.2-0.3	21191
0.3-0.4	10133
0.4-0.5	2805
0.5-0.6	218
0.6-0.7	24
0.7-0.8	0
0.8-0.85	1
0.85-0.9	6
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC255050
0.8904	High Similarity	NPC90839
0.8667	High Similarity	NPC288415
0.8667	High Similarity	NPC149908
0.8667	High Similarity	NPC31313
0.8667	High Similarity	NPC45906
0.8553	High Similarity	NPC93630
0.8421	Intermediate Similarity	NPC81006
0.7042	Intermediate Similarity	NPC112398
0.6618	Remote Similarity	NPC243635
0.6618	Remote Similarity	NPC151004
0.6618	Remote Similarity	NPC228980
0.6404	Remote Similarity	NPC168017
0.6264	Remote Similarity	NPC178632
0.6136	Remote Similarity	NPC124359
0.5926	Remote Similarity	NPC290231
0.5926	Remote Similarity	NPC206241
0.5926	Remote Similarity	NPC48448
0.5926	Remote Similarity	NPC180401
0.5926	Remote Similarity	NPC266383
0.5926	Remote Similarity	NPC68043
0.5926	Remote Similarity	NPC271803
0.5765	Remote Similarity	NPC80447
0.5765	Remote Similarity	NPC477002
0.5658	Remote Similarity	NPC319991
0.5612	Remote Similarity	NPC155985

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 NPC127553 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	101
0.1-0.2	2141
0.2-0.3	5079
0.3-0.4	1501
0.4-0.5	249
0.5-0.6	67
0.6-0.7	12
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
0.6618	Remote Similarity	NPD1823	Approved
0.6618	Remote Similarity	NPD1822	Approved
0.6618	Remote Similarity	NPD1821	Approved
0.6329	Remote Similarity	NPD2695	Approved
0.6329	Remote Similarity	NPD2697	Approved
0.6329	Remote Similarity	NPD2694	Approved
0.6329	Remote Similarity	NPD2696	Approved
0.6232	Remote Similarity	NPD7348	Clinical (unspecified phase)
0.6027	Remote Similarity	NPD6439	Phase 3
0.6	Remote Similarity	NPD8143	Approved
0.6	Remote Similarity	NPD8144	Approved
0.5854	Remote Similarity	NPD7535	Discontinued
0.5842	Remote Similarity	NPD7912	Approved
0.5842	Remote Similarity	NPD7987	Approved
0.5842	Remote Similarity	NPD7986	Approved
0.5842	Remote Similarity	NPD7911	Approved
0.5833	Remote Similarity	NPD312	Clinical (unspecified phase)
0.5753	Remote Similarity	NPD3727	Discontinued
0.5728	Remote Similarity	NPD8040	Discontinued
0.5673	Remote Similarity	NPD7646	Clinical (unspecified phase)
0.5673	Remote Similarity	NPD7989	Approved
0.5673	Remote Similarity	NPD7990	Approved

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