NPASS Compound

Structure

NPC140447 OpenBabel06302215272D 26 30 0 0 1 0 0 0 0 0999 V2000 1.0479 -1.2245 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5036 -0.4457 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0570 0.3383 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2569 0.7805 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8982 1.1073 0.0000 N 0 0 3 0 0 0 0 0 0 0 0 0 0.8982 0.2050 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1168 -0.2461 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6646 0.2050 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.5227 -0.0738 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8897 -0.8981 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7870 -0.9924 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3174 -0.2624 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9504 0.5618 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0531 0.6561 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5227 1.3861 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.6646 1.1073 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1168 1.5584 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.6266 1.0853 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5747 0.3918 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.3296 -0.8399 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2218 -0.9744 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2502 -2.8217 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9206 -3.6616 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1424 -2.6872 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7050 -3.3926 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 2 0 0 0 0 3 19 1 0 0 0 0 3 4 1 0 0 0 0 4 5 1 0 0 0 0 5 17 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 16 1 0 0 0 0 8 20 1 0 0 0 0 8 9 1 0 0 0 0 9 14 2 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 13 14 1 0 0 0 0 14 15 1 0 0 0 0 15 16 2 0 0 0 0 16 17 1 0 0 0 0 17 18 1 6 0 0 0 19 18 1 1 0 0 0 19 20 1 0 0 0 0 20 21 1 6 0 0 0 20 23 1 0 0 0 0 21 22 1 0 0 0 0 23 24 2 0 0 0 0 23 25 1 0 0 0 0 25 26 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	352.18
Volume:	361.535
LogP:	1.839
LogD:	2.163
LogS:	-2.677
# Rotatable Bonds:	3
TPSA:	62.13
# H-Bond Aceptor:	5
# H-Bond Donor:	1
# Rings:	5
# Heavy Atoms:	5

MedChem Properties

QED Drug-Likeness Score:	0.655
Synthetic Accessibility Score:	5.453
Fsp3:	0.524
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:	-5.067
MDCK Permeability:	3.095350257353857e-05
Pgp-inhibitor:	0.004
Pgp-substrate:	0.265
Human Intestinal Absorption (HIA):	0.027
20% Bioavailability (F20%):	0.016
30% Bioavailability (F30%):	0.041

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.986
Plasma Protein Binding (PPB):	69.11282348632812%
Volume Distribution (VD):	1.808
Pgp-substrate:	51.3237190246582%

ADMET: Metabolism

CYP1A2-inhibitor:	0.134
CYP1A2-substrate:	0.499
CYP2C19-inhibitor:	0.147
CYP2C19-substrate:	0.909
CYP2C9-inhibitor:	0.06
CYP2C9-substrate:	0.269
CYP2D6-inhibitor:	0.151
CYP2D6-substrate:	0.704
CYP3A4-inhibitor:	0.418
CYP3A4-substrate:	0.846

ADMET: Excretion

Clearance (CL):	7.89
Half-life (T1/2):	0.284

ADMET: Toxicity

hERG Blockers:	0.033
Human Hepatotoxicity (H-HT):	0.69
Drug-inuced Liver Injury (DILI):	0.218
AMES Toxicity:	0.762
Rat Oral Acute Toxicity:	0.95
Maximum Recommended Daily Dose:	0.95
Skin Sensitization:	0.259
Carcinogencity:	0.945
Eye Corrosion:	0.003
Eye Irritation:	0.015
Respiratory Toxicity:	0.966

Download Data

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

Natural Product: NPC140447

Natural Product ID:	NPC140447
*Common Name:**	XLHUHYFKFFGUFE-OQTQPSEISA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	XLHUHYFKFFGUFE-OQTQPSEISA-N
Standard InCHI:	InChI=1S/C21H24N2O3/c1-3-13-11-23-9-8-20-14-6-4-5-7-16(14)22-18(20)17(23)10-15(13)21(20,12-24)19(25)26-2/h3-7,15,17,24H,8-12H2,1-2H3/b13-3-/t15-,17-,20+,21-/m0/s1
SMILES:	C/C=C1/CN2CC[C@@]34c5ccccc5N=C3[C@@H]2C[C@@H]1[C@@]4(CO)C(=O)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000279] Alkaloids and derivatives [CHEMONTID:0002750] Corynanthean-type alkaloids

*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
NPO18923	Coleus xanthanthus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[12027731]
NPO10	Alexandrium ostenfeldii	Species	Pyrocystaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16872129]
NPO10	Alexandrium ostenfeldii	Species	Pyrocystaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[19572609]
NPO18923	Coleus xanthanthus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21640	Pygmaeopremna herbacea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO18923	Coleus xanthanthus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28069.1	Artemisia cana subsp. viscidula	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21313	Rabdosia lasiocarpa	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO1824	Callitris rhomboidea	Species	Cupressaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28069.1	Artemisia cana subsp. viscidula	Subspecies	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10	Alexandrium ostenfeldii	Species	Pyrocystaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO2744	Aphloia madagascariensis	Species	Aphloiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21640	Pygmaeopremna herbacea	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO7972	Solaster endeca	Species	Solasteridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13485	Prismatomeris sessiliflora	Species	Rubiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8358	Senecio halimifolius	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20028	Lethariella sernanderi	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18923	Coleus xanthanthus	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17662	Scutellaria glabrata	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO3679	Psilocybe baeocystis	Species	Strophariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO17897	Streptomyces albospinus	Species	Streptomycetaceae	Bacteria	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 NPC140447 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	176
0.1-0.2	925
0.2-0.3	3343
0.3-0.4	16570
0.4-0.5	16321
0.5-0.6	4414
0.6-0.7	811
0.7-0.8	133
0.8-0.85	3
0.85-0.9	0
0.9-0.95	1
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 NPC140447 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	128
0.1-0.2	422
0.2-0.3	761
0.3-0.4	1399
0.4-0.5	3522
0.5-0.6	2511
0.6-0.7	398
0.7-0.8	9
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