NPASS Compound

Structure

NPC81006 OpenBabel07101718252D 34 38 0 0 1 0 0 0 0 0999 V2000 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 3.0120 -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 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 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 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 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 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 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 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 4.3461 0.4759 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2531 1.3610 0.0000 C 0 0 1 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 5.2121 1.9759 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 3.3739 0.7102 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0948 0.8211 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 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 17 1 0 0 0 0 9 19 1 0 0 0 0 10 18 1 0 0 0 0 10 20 1 0 0 0 0 13 21 1 0 0 0 0 13 23 1 0 0 0 0 14 22 1 0 0 0 0 14 24 1 0 0 0 0 15 27 1 0 0 0 0 16 28 1 0 0 0 0 17 27 1 0 0 0 0 18 28 1 0 0 0 0 19 30 1 0 0 0 0 20 29 1 0 0 0 0 21 29 1 0 0 0 0 22 30 1 0 0 0 0 23 11 1 1 0 0 0 23 33 1 0 0 0 0 24 12 1 6 0 0 0 24 34 1 0 0 0 0 25 27 1 6 0 0 0 25 30 1 0 0 0 0 25 34 1 0 0 0 0 26 28 1 1 0 0 0 26 29 1 0 0 0 0 26 33 1 0 0 0 0 27 31 1 1 0 0 0 28 32 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	478.38
Volume:	507.216
LogP:	4.583
LogD:	3.763
LogS:	-4.782
# Rotatable Bonds:	0
TPSA:	65.4
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.532
Synthetic Accessibility Score:	5.925
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:	-4.899
MDCK Permeability:	1.4772454960620962e-05
Pgp-inhibitor:	0.059
Pgp-substrate:	0.741
Human Intestinal Absorption (HIA):	0.056
20% Bioavailability (F20%):	0.629
30% Bioavailability (F30%):	0.001

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.146
Plasma Protein Binding (PPB):	76.1029281616211%
Volume Distribution (VD):	1.09
Pgp-substrate:	11.556998252868652%

ADMET: Metabolism

CYP1A2-inhibitor:	0.008
CYP1A2-substrate:	0.261
CYP2C19-inhibitor:	0.022
CYP2C19-substrate:	0.871
CYP2C9-inhibitor:	0.001
CYP2C9-substrate:	0.025
CYP2D6-inhibitor:	0.735
CYP2D6-substrate:	0.772
CYP3A4-inhibitor:	0.092
CYP3A4-substrate:	0.099

ADMET: Excretion

Clearance (CL):	4.893
Half-life (T1/2):	0.05

ADMET: Toxicity

hERG Blockers:	0.341
Human Hepatotoxicity (H-HT):	0.702
Drug-inuced Liver Injury (DILI):	0.05
AMES Toxicity:	0.041
Rat Oral Acute Toxicity:	0.019
Maximum Recommended Daily Dose:	0.762
Skin Sensitization:	0.966
Carcinogencity:	0.324
Eye Corrosion:	0.004
Eye Irritation:	0.023
Respiratory Toxicity:	0.887

Download Data

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

Natural Product: NPC81006

Natural Product ID:	NPC81006
*Common Name:**	XBUGUOQUMLNGNN-BNNSEFEDSA-N
IUPAC Name:	n.a.
Synonyms:	(+)-Araguspongine C
Standard InCHIKey:	XBUGUOQUMLNGNN-BNNSEFEDSA-N
Standard InCHI:	InChI=1S/C28H50N2O4/c31-27-15-7-3-1-5-11-23-13-21-29-20-10-18-28(32,26(29)33-23)16-8-4-2-6-12-24-14-22-30(19-9-17-27)25(27)34-24/h23-26,31-32H,1-22H2/t23-,24-,25+,26+,27-,28-/m1/s1
SMILES:	C1CCC[C@]2(CCCN3CC[C@@H](CCCCCC[C@]4(CCCN5CC[C@@H](CC1)O[C@@H]45)O)O[C@@H]23)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL518547
PubChem CID:	5276744
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
NPO31288	Xestospongia exigua	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12444683]
NPO31288	Xestospongia exigua	Species	Petrosiidae	Eukaryota	n.a.	Red Sea	n.a.	PMID[12502314]
NPO31288	Xestospongia exigua	Species	Petrosiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[25580621]

☑ 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	2
MIC	1

Activity Type	# Activity
Organism	3

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.67	ug.mL-1	PMID[569203]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	0.28	ug.mL-1	PMID[569203]
NPT88	Organism	Mycobacterium tuberculosis	Mycobacterium tuberculosis	MIC	=	3940.0	nM	PMID[569203]

☑ 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 NPC81006 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	162
0.1-0.2	4145
0.2-0.3	22036
0.3-0.4	11578
0.4-0.5	4376
0.5-0.6	368
0.6-0.7	23
0.7-0.8	0
0.8-0.85	2
0.85-0.9	1
0.9-0.95	0
0.95-1	6

Similarity Score	Similarity Level	Natural Product ID
0.9737	High Similarity	NPC31313
0.9737	High Similarity	NPC288415
0.9737	High Similarity	NPC149908
0.9737	High Similarity	NPC45906
0.961	High Similarity	NPC93630
0.8974	High Similarity	NPC90839
0.8421	Intermediate Similarity	NPC255050
0.8421	Intermediate Similarity	NPC127553
0.6596	Remote Similarity	NPC168017
0.6582	Remote Similarity	NPC112398
0.6522	Remote Similarity	NPC124359
0.6458	Remote Similarity	NPC178632
0.6196	Remote Similarity	NPC471420
0.6145	Remote Similarity	NPC233034
0.6118	Remote Similarity	NPC126664
0.6118	Remote Similarity	NPC34291
0.6078	Remote Similarity	NPC313821
0.6024	Remote Similarity	NPC163134
0.6024	Remote Similarity	NPC471419
0.6	Remote Similarity	NPC477002
0.5978	Remote Similarity	NPC150557
0.5909	Remote Similarity	NPC476695
0.5909	Remote Similarity	NPC476694
0.5909	Remote Similarity	NPC476696
0.5882	Remote Similarity	NPC238646
0.5859	Remote Similarity	NPC470284
0.5794	Remote Similarity	NPC314387
0.5758	Remote Similarity	NPC470282
0.5755	Remote Similarity	NPC56298
0.5755	Remote Similarity	NPC471628
0.5747	Remote Similarity	NPC471418
0.5747	Remote Similarity	NPC474469
0.5732	Remote Similarity	NPC471421
0.5732	Remote Similarity	NPC233364
0.5714	Remote Similarity	NPC91036
0.5682	Remote Similarity	NPC475127
0.5682	Remote Similarity	NPC475715
0.5682	Remote Similarity	NPC473419
0.5682	Remote Similarity	NPC268922
0.5679	Remote Similarity	NPC293551
0.5673	Remote Similarity	NPC119225
0.5673	Remote Similarity	NPC470382
0.5673	Remote Similarity	NPC476261
0.5673	Remote Similarity	NPC471635
0.5673	Remote Similarity	NPC25033
0.566	Remote Similarity	NPC220111
0.5641	Remote Similarity	NPC475887
0.5632	Remote Similarity	NPC184150
0.5632	Remote Similarity	NPC141156
0.5625	Remote Similarity	NPC36927
0.5625	Remote Similarity	NPC271772
0.5607	Remote Similarity	NPC315036
0.5604	Remote Similarity	NPC315806
0.56	Remote Similarity	NPC52533

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 NPC81006 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	106
0.1-0.2	1777
0.2-0.3	4847
0.3-0.4	1974
0.4-0.5	302
0.5-0.6	133
0.6-0.7	11
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
0.6168	Remote Similarity	NPD8140	Approved
0.6145	Remote Similarity	NPD9440	Discontinued
0.6118	Remote Similarity	NPD9443	Clinical (unspecified phase)
0.6087	Remote Similarity	NPD8347	Approved
0.6087	Remote Similarity	NPD8345	Approved
0.6087	Remote Similarity	NPD8346	Approved
0.6078	Remote Similarity	NPD3190	Approved
0.6078	Remote Similarity	NPD3189	Approved
0.6078	Remote Similarity	NPD3191	Approved
0.6019	Remote Similarity	NPD8307	Discontinued
0.5895	Remote Similarity	NPD882	Phase 2
0.5895	Remote Similarity	NPD883	Phase 2
0.5872	Remote Similarity	NPD7646	Clinical (unspecified phase)
0.5854	Remote Similarity	NPD9455	Approved
0.5794	Remote Similarity	NPD3183	Approved
0.5794	Remote Similarity	NPD3184	Approved
0.5794	Remote Similarity	NPD3182	Approved
0.5794	Remote Similarity	NPD3185	Approved
0.5783	Remote Similarity	NPD393	Approved
0.5755	Remote Similarity	NPD4837	Approved
0.5755	Remote Similarity	NPD4835	Approved
0.5755	Remote Similarity	NPD4838	Approved
0.5755	Remote Similarity	NPD4836	Approved
0.573	Remote Similarity	NPD7535	Discontinued
0.5714	Remote Similarity	NPD8087	Discontinued
0.5699	Remote Similarity	NPD8143	Approved
0.5699	Remote Similarity	NPD8144	Approved
0.5641	Remote Similarity	NPD7348	Clinical (unspecified phase)
0.5625	Remote Similarity	NPD2691	Clinical (unspecified phase)
0.5604	Remote Similarity	NPD9653	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