NPASS Compound

Structure

NPC489254 OpenBabel06302216172D 37 40 0 0 1 0 0 0 0 0999 V2000 5.3908 -5.4334 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.5987 -4.4553 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8555 -3.7862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9045 -4.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1613 -3.4260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3692 -2.4479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3203 -2.1389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0634 -2.8080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0145 -2.4990 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.6261 -1.7788 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6750 -2.0878 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 0.0570 -2.0878 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8940 -1.7788 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.6372 -2.4479 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5882 -2.1389 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3314 -2.8080 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1235 -3.7862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1724 -4.0952 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4293 -3.4260 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9645 -5.0733 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.8666 -4.4553 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6587 -5.4334 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2825 -2.4990 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -1.1020 -0.8006 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3660 -3.0388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2218 -3.8479 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3660 -3.0388 0.0000 O 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 1.7321 0.0000 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 0.8660 1.5000 0.0000 C 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 0.0000 -0.0000 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8660 1.5000 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 0.8660 2.5000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5981 1.5000 0.0000 Br 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 8 2 0 0 0 0 3 4 1 0 0 0 0 4 5 2 0 0 0 0 5 6 1 0 0 0 0 6 7 2 0 0 0 0 6 10 1 0 0 0 0 7 8 1 0 0 0 0 8 9 1 0 0 0 0 10 11 2 0 0 0 0 11 28 1 0 0 0 0 11 12 1 0 0 0 0 12 13 2 0 0 0 0 12 29 1 0 0 0 0 13 14 1 0 0 0 0 13 26 1 0 0 0 0 14 15 1 0 0 0 0 14 25 1 6 0 0 0 15 20 2 0 0 0 0 15 16 1 0 0 0 0 16 17 2 0 0 0 0 17 18 1 0 0 0 0 17 24 1 0 0 0 0 18 19 2 0 0 0 0 18 22 1 0 0 0 0 19 20 1 0 0 0 0 19 21 1 0 0 0 0 22 23 1 0 0 0 0 26 27 2 0 0 0 0 26 28 1 0 0 0 0 29 34 2 0 0 0 0 29 30 1 0 0 0 0 30 31 2 0 0 0 0 31 32 1 0 0 0 0 31 37 1 0 0 0 0 32 33 2 0 0 0 0 32 36 1 0 0 0 0 33 34 1 0 0 0 0 33 35 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	819.69
Volume:	541.548
LogP:	6.256
LogD:	2.792
LogS:	-4.756
# Rotatable Bonds:	6
TPSA:	85.22
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	4
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.244
Synthetic Accessibility Score:	3.636
Fsp3:	0.115
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.924
MDCK Permeability:	1.763986438163556e-05
Pgp-inhibitor:	1.0
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.776
20% Bioavailability (F20%):	0.029
30% Bioavailability (F30%):	0.748

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019
Plasma Protein Binding (PPB):	105.23783111572266%
Volume Distribution (VD):	0.334
Pgp-substrate:	10.899163246154785%

ADMET: Metabolism

CYP1A2-inhibitor:	0.694
CYP1A2-substrate:	0.183
CYP2C19-inhibitor:	0.775
CYP2C19-substrate:	0.174
CYP2C9-inhibitor:	0.846
CYP2C9-substrate:	0.084
CYP2D6-inhibitor:	0.024
CYP2D6-substrate:	0.121
CYP3A4-inhibitor:	0.182
CYP3A4-substrate:	0.169

ADMET: Excretion

Clearance (CL):	0.8
Half-life (T1/2):	0.055

ADMET: Toxicity

hERG Blockers:	0.029
Human Hepatotoxicity (H-HT):	0.922
Drug-inuced Liver Injury (DILI):	0.957
AMES Toxicity:	0.013
Rat Oral Acute Toxicity:	0.894
Maximum Recommended Daily Dose:	0.989
Skin Sensitization:	0.585
Carcinogencity:	0.136
Eye Corrosion:	0.003
Eye Irritation:	0.032
Respiratory Toxicity:	0.842

Download Data

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

Natural Product: NPC489254

Natural Product ID:	NPC489254
*Common Name:**	ANVFNNNDDSHEGE-JNONIEOKSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	ANVFNNNDDSHEGE-JNONIEOKSA-N
Standard InCHI:	InChI=1S/C26H17Br5O6/c1-35-19-4-3-11(5-14(19)27)6-20-21(12-7-15(28)24(33)16(29)8-12)22(26(34)37-20)23(32)13-9-17(30)25(36-2)18(31)10-13/h3-10,23,32-33H,1-2H3/b20-6-/t23-/m0/s1
SMILES:	COc1ccc(cc1Br)/C=C1/C(=C([C@H](c2cc(c(c(c2)Br)OC)Br)O)C(=O)O1)c1cc(c(c(c1)Br)O)Br
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	n.a.
PubChem CID:	102313457
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002341] Phenol ethers [CHEMONTID:0000138] Anisoles

*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
NPO40655	Synoicum sp. Ascidian	Strain	Polyclinidae	Eukaryota	n.a.	n.a.	n.a.	PMID[31967465]

☑ 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
IC50	2
MIC	6

Activity Type	# Activity
Individual Protein	2
Organism	6

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1821	Individual Protein	Sortase	Staphylococcus aureus	IC50	>	156000.0	nM	PMID[31967465]
NPT1087	Individual Protein	Isocitrate lyase	Candida albicans	IC50	=	150000.0	nM	PMID[31967465]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	32.0	ug.mL-1	PMID[31967465]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	=	64.0	ug.mL-1	PMID[31967465]
NPT1531	Organism	Enterococcus faecium	Enterococcus faecium	MIC	>	128.0	ug.mL-1	PMID[31967465]
NPT1190	Organism	Salmonella enterica	Salmonella enterica	MIC	=	64.0	ug.mL-1	PMID[31967465]
NPT25245	ORGANISM	Proteus hauseri	Proteus hauseri	MIC	=	8.0	ug.mL-1	PMID[31967465]
NPT173	Organism	Klebsiella pneumoniae	Klebsiella pneumoniae	MIC	>	128.0	ug.mL-1	PMID[31967465]

☑ 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 NPC489254 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	330
0.1-0.2	1454
0.2-0.3	4000
0.3-0.4	10845
0.4-0.5	8236
0.5-0.6	6546
0.6-0.7	10649
0.7-0.8	601
0.8-0.85	25
0.85-0.9	4
0.9-0.95	0
0.95-1	7

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 NPC489254 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	282
0.1-0.2	892
0.2-0.3	1689
0.3-0.4	2847
0.4-0.5	1947
0.5-0.6	1153
0.6-0.7	321
0.7-0.8	19
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