NPASS Compound

Structure

NPC111349 OpenBabel06302216122D 22 24 0 0 0 0 0 0 0 0999 V2000 0.8660 -2.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 -1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -1.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 0.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 0.5000 0.0000 C 0 0 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 -0.8660 1.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7321 2.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4641 3.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3301 3.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1962 2.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0622 1.5000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 0 0 0 2 3 1 0 0 0 0 3 16 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 14 1 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 8 13 2 0 0 0 0 8 9 1 0 0 0 0 9 10 2 0 0 0 0 10 11 1 0 0 0 0 10 21 1 0 0 0 0 11 12 2 0 0 0 0 11 19 1 0 0 0 0 12 13 1 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 15 16 1 0 0 0 0 15 17 1 0 0 0 0 17 18 1 0 0 0 0 19 20 1 0 0 0 0 21 22 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	298.12
Volume:	310.921
LogP:	3.932
LogD:	3.585
LogS:	-5.571
# Rotatable Bonds:	4
TPSA:	36.92
# H-Bond Aceptor:	4
# H-Bond Donor:	0
# Rings:	3
# Heavy Atoms:	4

MedChem Properties

QED Drug-Likeness Score:	0.682
Synthetic Accessibility Score:	1.997
Fsp3:	0.222
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected
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:	-4.906
MDCK Permeability:	6.920902524143457e-05
Pgp-inhibitor:	0.875
Pgp-substrate:	0.871
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.044
30% Bioavailability (F30%):	0.519

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.152
Plasma Protein Binding (PPB):	78.88396453857422%
Volume Distribution (VD):	0.657
Pgp-substrate:	9.781105041503906%

ADMET: Metabolism

CYP1A2-inhibitor:	0.94
CYP1A2-substrate:	0.981
CYP2C19-inhibitor:	0.759
CYP2C19-substrate:	0.899
CYP2C9-inhibitor:	0.277
CYP2C9-substrate:	0.933
CYP2D6-inhibitor:	0.256
CYP2D6-substrate:	0.952
CYP3A4-inhibitor:	0.755
CYP3A4-substrate:	0.496

ADMET: Excretion

Clearance (CL):	10.279
Half-life (T1/2):	0.512

ADMET: Toxicity

hERG Blockers:	0.117
Human Hepatotoxicity (H-HT):	0.121
Drug-inuced Liver Injury (DILI):	0.942
AMES Toxicity:	0.621
Rat Oral Acute Toxicity:	0.125
Maximum Recommended Daily Dose:	0.703
Skin Sensitization:	0.942
Carcinogencity:	0.142
Eye Corrosion:	0.045
Eye Irritation:	0.872
Respiratory Toxicity:	0.567

Download Data

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

Natural Product: NPC111349

Natural Product ID:	NPC111349
*Common Name:**	FZHIPPXJJHNYSV-UHFFFAOYSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	FZHIPPXJJHNYSV-UHFFFAOYSA-N
Standard InCHI:	InChI=1S/C18H18O4/c1-19-13-7-12-6-5-11-8-15(20-2)16(21-3)10-14(11)18(12)17(9-13)22-4/h5-10H,1-4H3
SMILES:	COc1cc2ccc3cc(c(cc3c2c(c1)OC)OC)OC
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	101995283
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0000025] Phenanthrenes 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
NPO20097	Thermobifida alba	Species	0cardiopsaceae	Bacteria	n.a.	n.a.	n.a.	PMID[11430001]
NPO9419	Enterobacter cloacae	Species	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[25427277]
NPO24359	Streptomyces cacaoi	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	PMID[27642865]
NPO26245	Styracaster caroli	Species	Porcellanasteridae	Eukaryota	n.a.	n.a.	n.a.	PMID[8145229]
NPO8460	Pedicularis torta	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20097	Thermobifida alba	Species	0cardiopsaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO24359	Streptomyces cacaoi	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO9419	Enterobacter cloacae	Species	Enterobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO13147	Euphorbia cyparissias	Species	Euphorbiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19605	Tara spinosa	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26245	Styracaster caroli	Species	Porcellanasteridae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6054	Sinularia brongersmai	Species	Alcyoniidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10024	Tylecodon wallichii	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO8559	Calophyllum venulosum	Species	Calophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11319	Laurencia hybrida	Species	Rhodomelaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6962	Cetraria delisei	Species	Parmeliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11181	Juniperus bermudiana	Species	Cupressaceae	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 NPC111349 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	608
0.1-0.2	2105
0.2-0.3	6265
0.3-0.4	12678
0.4-0.5	3780
0.5-0.6	4682
0.6-0.7	8207
0.7-0.8	3661
0.8-0.85	498
0.85-0.9	177
0.9-0.95	34
0.95-1	2

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 NPC111349 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	520
0.1-0.2	986
0.2-0.3	1673
0.3-0.4	2812
0.4-0.5	1626
0.5-0.6	902
0.6-0.7	533
0.7-0.8	90
0.8-0.85	8
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