NPASS Compound

Structure

CID237535 OpenBabel06191716042D 26 30 0 0 1 0 0 0 0 0999 V2000 1.2194 2.1872 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3954 2.2134 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0349 2.5619 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.4375 1.5366 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5143 1.4516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4892 0.4839 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9204 -0.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8381 1.4516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7342 -0.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5966 -0.2990 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8381 -0.4839 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9204 1.2668 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6762 0.9677 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6546 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7342 1.2668 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8381 1.4516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5966 1.2668 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1654 0.4839 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6762 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.0000 0.9677 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.6546 0.9677 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.6762 0.9677 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 -5.4375 -0.5688 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4352 2.1872 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8381 2.4194 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 12 1 0 0 0 0 2 17 1 0 0 0 0 3 17 1 0 0 0 0 4 21 1 0 0 0 0 5 22 1 0 0 0 0 6 7 1 0 0 0 0 6 12 1 0 0 0 0 7 23 1 0 0 0 0 8 13 1 0 0 0 0 8 20 1 0 0 0 0 9 14 1 0 0 0 0 10 18 1 0 0 0 0 10 19 1 0 0 0 0 11 19 1 0 0 0 0 11 23 1 0 0 0 0 12 20 1 6 0 0 0 13 17 1 0 0 0 0 13 19 1 1 0 0 0 14 21 1 0 0 0 0 14 24 2 0 0 0 0 15 18 1 0 0 0 0 15 21 1 0 0 0 0 15 25 2 0 0 0 0 16 20 1 0 0 0 0 16 22 1 0 0 0 0 16 26 2 0 0 0 0 17 18 1 0 0 0 0 18 9 1 1 0 0 0 19 22 1 6 0 0 0 20 23 1 6 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	359.22
Volume:	363.145
LogP:	2.261
LogD:	1.641
LogS:	-4.177
# Rotatable Bonds:	0
TPSA:	60.93
# H-Bond Aceptor:	6
# H-Bond Donor:	0
# Rings:	6
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.608
Synthetic Accessibility Score:	6.558
Fsp3:	0.85
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Accepted
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.366
MDCK Permeability:	1.0958955499518197e-05
Pgp-inhibitor:	0.038
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.708
20% Bioavailability (F20%):	0.504
30% Bioavailability (F30%):	0.996

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.56
Plasma Protein Binding (PPB):	31.051586151123047%
Volume Distribution (VD):	1.366
Pgp-substrate:	74.36845397949219%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.781
CYP2C19-inhibitor:	0.27
CYP2C19-substrate:	0.969
CYP2C9-inhibitor:	0.455
CYP2C9-substrate:	0.274
CYP2D6-inhibitor:	0.003
CYP2D6-substrate:	0.149
CYP3A4-inhibitor:	0.861
CYP3A4-substrate:	0.949

ADMET: Excretion

Clearance (CL):	5.508
Half-life (T1/2):	0.599

ADMET: Toxicity

hERG Blockers:	0.009
Human Hepatotoxicity (H-HT):	0.393
Drug-inuced Liver Injury (DILI):	0.173
AMES Toxicity:	0.205
Rat Oral Acute Toxicity:	0.415
Maximum Recommended Daily Dose:	0.911
Skin Sensitization:	0.107
Carcinogencity:	0.937
Eye Corrosion:	0.003
Eye Irritation:	0.009
Respiratory Toxicity:	0.042

Download Data

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

Natural Product: NPC237535

Natural Product ID:	NPC237535
*Common Name:**	RTNMRJRMTGSUAE-DWPFRNKMSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	RTNMRJRMTGSUAE-DWPFRNKMSA-N
Standard InCHI:	InChI=1S/C20H29N3O3/c1-12-6-7-23-11-19-10-18(9-14(24)21(4)15(18)25)17(2,3)13(19)8-20(12,23)16(26)22(19)5/h12-13H,6-11H2,1-5H3/t12-,13-,18-,19+,20+/m1/s1
SMILES:	C[C@@H]1CCN2C[C@@]34C[C@@]5(CC(=O)N(C)C5=O)C(C)(C)[C@H]3C[C@@]12C(=O)N4C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL3358708
PubChem CID:	70698047
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000130] Azaspirodecane derivatives

*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
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10075772]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16155971]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19824618]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	mycelium	n.a.	PMID[21667999]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	latex	n.a.	PMID[21854017]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[324959]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	Eukaryota	n.a.	n.a.	n.a.	Database[Title]
NPO8911	Aspergillus aculeatus	Species	Aspergillaceae	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
MIC	1

Activity Type	# Activity
Organism	1

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT115	Organism	Mycobacterium tuberculosis H37Ra	Mycobacterium tuberculosis H37Ra	MIC	=	25.0	ug.mL-1	PMID[519017]

☑ 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 NPC237535 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	308
0.1-0.2	16462
0.2-0.3	16000
0.3-0.4	8561
0.4-0.5	1220
0.5-0.6	128
0.6-0.7	17
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
0.6263	Remote Similarity	NPC34811
0.6222	Remote Similarity	NPC68043
0.6222	Remote Similarity	NPC48448
0.6222	Remote Similarity	NPC180401
0.6222	Remote Similarity	NPC266383
0.6222	Remote Similarity	NPC271803
0.6222	Remote Similarity	NPC206241
0.6222	Remote Similarity	NPC290231
0.6064	Remote Similarity	NPC80447
0.5946	Remote Similarity	NPC97336
0.5806	Remote Similarity	NPC120167
0.5806	Remote Similarity	NPC473442
0.5763	Remote Similarity	NPC309731

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 NPC237535 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	143
0.1-0.2	2880
0.2-0.3	4665
0.3-0.4	1221
0.4-0.5	217
0.5-0.6	21
0.6-0.7	2
0.7-0.8	1
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
0.6667	Remote Similarity	NPD7155	Clinical (unspecified phase)
0.6463	Remote Similarity	NPD605	Clinical (unspecified phase)
0.6275	Remote Similarity	NPD6934	Discontinued
0.6262	Remote Similarity	NPD5359	Clinical (unspecified phase)
0.587	Remote Similarity	NPD1439	Clinical (unspecified phase)
0.566	Remote Similarity	NPD2682	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