NPASS Compound

Structure

NPC181768 OpenBabel06302215572D 25 27 0 0 1 0 0 0 0 0999 V2000 -2.7540 1.9207 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7540 0.9207 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.7790 0.6982 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9972 0.0747 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5633 -0.8262 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.5633 -1.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9972 -2.7272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7790 -3.3507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7540 -3.5732 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.7289 -3.3507 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1628 -4.2517 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5107 -2.7272 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9446 -1.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9446 -0.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8106 -0.3262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6767 -0.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6767 -1.8262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8106 -2.3262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8106 -3.3262 0.0000 Cl 0 0 0 0 0 0 0 0 0 0 0 0 -7.5427 -2.3262 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8106 0.6738 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5107 0.0747 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2926 0.6982 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7289 0.6982 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 2 1 1 1 0 0 0 2 3 1 0 0 0 0 2 24 1 0 0 0 0 4 3 1 6 0 0 0 4 5 1 0 0 0 0 4 25 1 0 0 0 0 5 6 1 6 0 0 0 5 25 1 0 0 0 0 6 7 2 0 0 0 0 7 8 1 0 0 0 0 8 9 2 0 0 0 0 9 10 1 0 0 0 0 10 11 2 0 0 0 0 10 12 1 0 0 0 0 12 13 1 0 0 0 0 13 18 2 0 0 0 0 13 14 1 0 0 0 0 14 15 2 0 0 0 0 14 22 1 0 0 0 0 15 16 1 0 0 0 0 15 21 1 0 0 0 0 16 17 2 0 0 0 0 17 18 1 0 0 0 0 17 20 1 0 0 0 0 18 19 1 0 0 0 0 22 23 2 0 0 0 0 22 24 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	364.07
Volume:	343.712
LogP:	3.523
LogD:	2.351
LogS:	-3.211
# Rotatable Bonds:	0
TPSA:	96.36
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	3
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.542
Synthetic Accessibility Score:	4.611
Fsp3:	0.333
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:	-4.793
MDCK Permeability:	2.049574140983168e-05
Pgp-inhibitor:	0.011
Pgp-substrate:	0.492
Human Intestinal Absorption (HIA):	0.005
20% Bioavailability (F20%):	0.011
30% Bioavailability (F30%):	0.038

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.111
Plasma Protein Binding (PPB):	96.48767852783203%
Volume Distribution (VD):	0.636
Pgp-substrate:	2.4143002033233643%

ADMET: Metabolism

CYP1A2-inhibitor:	0.754
CYP1A2-substrate:	0.106
CYP2C19-inhibitor:	0.166
CYP2C19-substrate:	0.072
CYP2C9-inhibitor:	0.679
CYP2C9-substrate:	0.914
CYP2D6-inhibitor:	0.716
CYP2D6-substrate:	0.294
CYP3A4-inhibitor:	0.438
CYP3A4-substrate:	0.23

ADMET: Excretion

Clearance (CL):	13.023
Half-life (T1/2):	0.788

ADMET: Toxicity

hERG Blockers:	0.122
Human Hepatotoxicity (H-HT):	0.693
Drug-inuced Liver Injury (DILI):	0.939
AMES Toxicity:	0.719
Rat Oral Acute Toxicity:	0.831
Maximum Recommended Daily Dose:	0.961
Skin Sensitization:	0.835
Carcinogencity:	0.904
Eye Corrosion:	0.01
Eye Irritation:	0.4
Respiratory Toxicity:	0.967

Download Data

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

Natural Product: NPC181768

Natural Product ID:	NPC181768
*Common Name:**	WYZWZEOGROVVHK-HBELNICQSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	WYZWZEOGROVVHK-HBELNICQSA-N
Standard InCHI:	InChI=1S/C18H17ClO6/c1-9-6-15-14(25-15)5-3-2-4-10(20)7-11-16(18(23)24-9)12(21)8-13(22)17(11)19/h2-5,8-9,14-15,21-22H,6-7H2,1H3/b4-2+,5-3-/t9-,14+,15-/m0/s1
SMILES:	C[C@H]1C[C@H]2[C@@H](/C=CC=CC(=O)Cc3c(c(cc(c3Cl)O)O)C(=O)O1)O2
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	n.a.
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0000176] Benzoic acids and derivatives [CHEMONTID:0001248] Hydroxybenzoic acid 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
NPO15986	Alangium chinense	Species	Cornaceae	Eukaryota	Roots	n.a.	n.a.	PMID[23734721]
NPO26705	Rhodiola kirilowii	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15986	Alangium chinense	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15986	Alangium chinense	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26705	Rhodiola kirilowii	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26705	Rhodiola kirilowii	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO15986	Alangium chinense	Species	Cornaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26705	Rhodiola kirilowii	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9334	Strychnos mattogrossensis	Species	Loganiaceae	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 NPC181768 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	393
0.1-0.2	1903
0.2-0.3	5277
0.3-0.4	11345
0.4-0.5	7419
0.5-0.6	6600
0.6-0.7	7959
0.7-0.8	1720
0.8-0.85	58
0.85-0.9	6
0.9-0.95	9
0.95-1	8

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 NPC181768 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	354
0.1-0.2	1075
0.2-0.3	2074
0.3-0.4	2837
0.4-0.5	1825
0.5-0.6	733
0.6-0.7	231
0.7-0.8	21
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