NPASS Compound

Structure

NPC243106 OpenBabel07101719162D 25 26 0 0 1 0 0 0 0 0999 V2000 -3.3784 -4.5589 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9716 -3.6453 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3729 -4.6634 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9771 -3.5408 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7796 -5.5769 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9135 0.5933 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 0.8090 -1.4013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7796 1.0933 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 -0.1691 -1.6092 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 -0.5759 -2.5227 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1809 -6.5950 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9135 -0.4067 0.0000 C 0 0 3 0 0 0 0 0 0 0 0 0 1.7796 2.0933 0.0000 Br 0 0 0 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 -7.1754 -6.6995 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.5931 -7.4040 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 -5.7742 -5.6815 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 0.0119 -3.3317 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 2 1 0 0 0 0 1 3 1 0 0 0 0 2 4 1 0 0 0 0 3 5 1 0 0 0 0 4 20 1 0 0 0 0 5 21 1 0 0 0 0 6 9 2 0 0 0 0 6 15 1 0 0 0 0 7 10 2 0 0 0 0 7 15 1 0 0 0 0 8 11 1 0 0 0 0 8 15 1 0 0 0 0 9 12 1 0 0 0 0 9 16 1 0 0 0 0 10 12 1 0 0 0 0 10 17 1 0 0 0 0 11 13 1 0 0 0 0 11 22 2 0 0 0 0 12 23 2 0 0 0 0 13 20 1 0 0 0 0 13 24 2 0 0 0 0 14 18 2 0 0 0 0 14 19 1 0 0 0 0 14 21 1 0 0 0 0 15 25 1 0 0 0 0 22 25 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	474.99
Volume:	354.986
LogP:	1.079
LogD:	0.343
LogS:	-2.314
# Rotatable Bonds:	9
TPSA:	129.66
# H-Bond Aceptor:	8
# H-Bond Donor:	5
# Rings:	2
# Heavy Atoms:	10

MedChem Properties

QED Drug-Likeness Score:	0.251
Synthetic Accessibility Score:	3.919
Fsp3:	0.467
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Accepted
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.166
MDCK Permeability:	1.8660843124962412e-05
Pgp-inhibitor:	0.998
Pgp-substrate:	0.001
Human Intestinal Absorption (HIA):	0.449
20% Bioavailability (F20%):	0.881
30% Bioavailability (F30%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.874
Plasma Protein Binding (PPB):	67.47906494140625%
Volume Distribution (VD):	0.726
Pgp-substrate:	54.964168548583984%

ADMET: Metabolism

CYP1A2-inhibitor:	0.142
CYP1A2-substrate:	0.237
CYP2C19-inhibitor:	0.273
CYP2C19-substrate:	0.064
CYP2C9-inhibitor:	0.167
CYP2C9-substrate:	0.103
CYP2D6-inhibitor:	0.658
CYP2D6-substrate:	0.321
CYP3A4-inhibitor:	0.226
CYP3A4-substrate:	0.139

ADMET: Excretion

Clearance (CL):	1.223
Half-life (T1/2):	0.477

ADMET: Toxicity

hERG Blockers:	0.291
Human Hepatotoxicity (H-HT):	0.684
Drug-inuced Liver Injury (DILI):	0.658
AMES Toxicity:	0.998
Rat Oral Acute Toxicity:	0.809
Maximum Recommended Daily Dose:	0.716
Skin Sensitization:	0.798
Carcinogencity:	0.977
Eye Corrosion:	0.003
Eye Irritation:	0.008
Respiratory Toxicity:	0.942

Download Data

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

Natural Product: NPC243106

Natural Product ID:	NPC243106
*Common Name:**	Clavatadine D
IUPAC Name:	7,9-dibromo-N-[5-(diaminomethylideneamino)pentyl]-8-oxo-1-oxa-2-azaspiro[4.5]deca-2,6,9-triene-3-carboxamide
Synonyms:	Clavatadine D
Standard InCHIKey:	OTXDUXAJSDNSCU-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C15H19Br2N5O3/c16-9-6-15(7-10(17)12(9)23)8-11(22-25-15)13(24)20-4-2-1-3-5-21-14(18)19/h6-7H,1-5,8H2,(H,20,24)(H4,18,19,21)
SMILES:	O=C(C1=NOC2(C1)C=C(Br)C(=O)C(=C2)Br)NCCCCCNC(=N)N
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL550969
PubChem CID:	44139244
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002490] Azolines [CHEMONTID:0002211] Isoxazolines

*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
NPO13261	Suberea clavata	Species	Aplysinellidae	Eukaryota	n.a.	Australian	n.a.	PMID[19379003]
NPO13261	Suberea clavata	Species	Aplysinellidae	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
Others	2

Activity Type	# Activity
Individual Protein	2

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT4197	Individual Protein	Coagulation factor XI	Homo sapiens	Inhibition	=	30.0	%	PMID[463382]
NPT4655	Individual Protein	Coagulation factor IX	Homo sapiens	Inhibition	<	5.0	%	PMID[463382]

☑ 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 NPC243106 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	144
0.1-0.2	11738
0.2-0.3	25502
0.3-0.4	4795
0.4-0.5	484
0.5-0.6	18
0.6-0.7	12
0.7-0.8	2
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC45830
0.7273	Intermediate Similarity	NPC145149
0.7213	Intermediate Similarity	NPC260270
0.7132	Intermediate Similarity	NPC289324
0.6772	Remote Similarity	NPC470892
0.6772	Remote Similarity	NPC172626
0.6718	Remote Similarity	NPC181086
0.6718	Remote Similarity	NPC304257
0.6617	Remote Similarity	NPC81079
0.6378	Remote Similarity	NPC313173
0.6349	Remote Similarity	NPC66855
0.6324	Remote Similarity	NPC202166
0.6324	Remote Similarity	NPC300912
0.6324	Remote Similarity	NPC473262
0.6324	Remote Similarity	NPC473261
0.6279	Remote Similarity	NPC158672
0.6279	Remote Similarity	NPC1702
0.6136	Remote Similarity	NPC477220
0.6056	Remote Similarity	NPC130714
0.5912	Remote Similarity	NPC473683
0.5704	Remote Similarity	NPC470886
0.5625	Remote Similarity	NPC477121

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 NPC243106 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	94
0.1-0.2	803
0.2-0.3	6261
0.3-0.4	1886
0.4-0.5	105
0.5-0.6	1
0.6-0.7	0
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
		NPD

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