NPASS Compound

Structure

NPC253599 OpenBabel06302216012D 29 32 0 0 1 0 0 0 0 0999 V2000 -2.9613 -3.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9613 -2.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0953 -2.1180 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.2293 -2.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3633 -2.1180 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.5878 -2.4271 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1756 -1.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5878 -0.8090 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3633 -1.1180 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.2293 -0.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0953 -1.1180 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.9613 -0.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8274 -1.1180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8274 -2.1180 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6934 -2.6180 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9613 0.3820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8274 0.8820 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0953 0.8820 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.0953 1.8820 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5388 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5388 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4049 1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2709 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2709 -0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4049 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4049 -2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5878 0.8090 0.0000 N 0 3 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0000 0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 3 2 1 6 0 0 0 3 4 1 0 0 0 0 3 11 1 0 0 0 0 4 5 1 0 0 0 0 5 9 1 0 0 0 0 5 6 1 0 0 0 0 6 7 1 0 0 0 0 8 7 1 1 0 0 0 8 28 1 0 0 0 0 8 9 1 0 0 0 0 8 20 1 0 0 0 0 9 10 1 1 0 0 0 10 11 1 0 0 0 0 11 12 1 1 0 0 0 12 13 2 0 0 0 0 12 16 1 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 16 17 2 0 0 0 0 16 18 1 0 0 0 0 18 19 1 0 0 0 0 20 25 2 0 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 21 27 1 0 0 0 0 22 23 1 0 0 0 0 23 24 2 0 0 0 0 24 25 1 0 0 0 0 25 26 1 0 0 0 0 27 28 2 0 0 0 0 28 29 1 0 0 0 0 M CHG 1 27 1 M END $$$$

Physi-Chem Properties

Molecular Weight:	400.2
Volume:	404.968
LogP:	2.664
LogD:	2.644
LogS:	-3.447
# Rotatable Bonds:	5
TPSA:	88.1
# H-Bond Aceptor:	7
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.458
Synthetic Accessibility Score:	4.871
Fsp3:	0.545
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
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:	-4.661
MDCK Permeability:	1.6009706087061204e-05
Pgp-inhibitor:	0.162
Pgp-substrate:	0.13
Human Intestinal Absorption (HIA):	0.013
20% Bioavailability (F20%):	0.448
30% Bioavailability (F30%):	0.604

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.997
Plasma Protein Binding (PPB):	68.15438079833984%
Volume Distribution (VD):	0.984
Pgp-substrate:	36.393890380859375%

ADMET: Metabolism

CYP1A2-inhibitor:	0.099
CYP1A2-substrate:	0.711
CYP2C19-inhibitor:	0.439
CYP2C19-substrate:	0.909
CYP2C9-inhibitor:	0.59
CYP2C9-substrate:	0.208
CYP2D6-inhibitor:	0.929
CYP2D6-substrate:	0.708
CYP3A4-inhibitor:	0.906
CYP3A4-substrate:	0.894

ADMET: Excretion

Clearance (CL):	8.277
Half-life (T1/2):	0.772

ADMET: Toxicity

hERG Blockers:	0.359
Human Hepatotoxicity (H-HT):	0.516
Drug-inuced Liver Injury (DILI):	0.409
AMES Toxicity:	0.254
Rat Oral Acute Toxicity:	0.878
Maximum Recommended Daily Dose:	0.95
Skin Sensitization:	0.656
Carcinogencity:	0.908
Eye Corrosion:	0.003
Eye Irritation:	0.011
Respiratory Toxicity:	0.958

Download Data

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

Natural Product: NPC253599

Natural Product ID:	NPC253599
*Common Name:**	IXWWTVSMMIIIFZ-JCIDKMOXSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	IXWWTVSMMIIIFZ-JCIDKMOXSA-N
Standard InCHI:	InChI=1S/C22H28N2O5/c1-4-13-11-24-9-8-22(19-16(23-21(22)27)6-5-7-17(19)25)18(24)10-14(13)15(12-28-2)20(26)29-3/h5-7,12-14,18,25H,4,8-11H2,1-3H3,(H,23,27)/p+1/b15-12+/t13-,14-,18-,22-/m0/s1
SMILES:	CC[C@H]1CN2CC[C@]3([C@@H]2C[C@@H]1/C(=COC)/C(=O)OC)c1c(cccc1O)[NH+]=C3O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	102232176
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0000013] Amino acids, peptides, and analogues [CHEMONTID:0000347] Amino acids and derivatives [CHEMONTID:0001878] Beta amino acids and 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
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	whole plant	n.a.	PMID[15635221]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[17067155]
NPO2677	Paralemnalia clavata	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18247571]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23517479]
NPO8554	Cryptocarya lividula	Species	Lauraceae	Eukaryota	n.a.	leaf	n.a.	PMID[27032214]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO1996	Penstemon gentianoides	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1569	Mitragyna speciosa	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10533	Ixeris chinensis	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4209	Knautia montana	Species	Caprifoliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO25675	Anthyllis onobrychoides	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO317	Corticium simplex	Species	Plakinidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8453	Euphorbia pannonica	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6163	Picris conyzoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2677	Paralemnalia clavata	Species	Nephtheidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8554	Cryptocarya lividula	Species	Lauraceae	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

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

☑ 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 NPC253599 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	230
0.1-0.2	1046
0.2-0.3	3702
0.3-0.4	11739
0.4-0.5	13194
0.5-0.6	10500
0.6-0.7	2084
0.7-0.8	170
0.8-0.85	20
0.85-0.9	12
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID

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 NPC253599 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	152
0.1-0.2	445
0.2-0.3	673
0.3-0.4	1380
0.4-0.5	2457
0.5-0.6	3211
0.6-0.7	817
0.7-0.8	15
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

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