NPASS Compound

Structure

NPC489246 OpenBabel06302215162D 36 39 0 0 1 0 0 0 0 0999 V2000 3.3956 -0.4483 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6068 0.1248 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1.7161 -0.2718 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6142 -1.2415 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9273 0.3013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9273 1.2763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7161 1.8494 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6068 1.4528 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3956 2.0259 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2937 2.9956 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4029 3.3921 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6142 2.8190 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3010 4.3618 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 4.0824 3.5687 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 1.5776 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3013 2.5049 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5731 0.7888 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.2618 -0.1862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1062 0.3013 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9506 -0.1862 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9506 -1.1612 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1062 -1.6487 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2618 -1.1612 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1062 -2.6237 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -4.7950 -1.6487 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4175 1.2763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4175 2.2513 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2618 2.7388 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1062 2.2513 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1062 1.2763 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2618 0.7888 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9506 0.7888 0.0000 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.9506 2.7388 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2618 3.7138 0.0000 Br 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 -0.3013 -0.9273 0.0000 O 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 4 2 0 0 0 0 3 5 1 0 0 0 0 5 35 1 0 0 0 0 5 6 2 0 0 0 0 6 7 1 0 0 0 0 6 15 1 0 0 0 0 7 12 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 14 1 0 0 0 0 11 12 1 0 0 0 0 11 13 1 0 0 0 0 15 16 2 0 0 0 0 15 17 1 0 0 0 0 17 18 1 6 0 0 0 17 26 1 0 0 0 0 17 35 1 0 0 0 0 18 23 2 0 0 0 0 18 19 1 0 0 0 0 19 20 2 0 0 0 0 20 21 1 0 0 0 0 21 22 2 0 0 0 0 21 25 1 0 0 0 0 22 23 1 0 0 0 0 22 24 1 0 0 0 0 26 31 2 0 0 0 0 26 27 1 0 0 0 0 27 28 2 0 0 0 0 28 29 1 0 0 0 0 28 34 1 0 0 0 0 29 30 2 0 0 0 0 29 33 1 0 0 0 0 30 31 1 0 0 0 0 30 32 1 0 0 0 0 35 36 2 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	741.75
Volume:	511.122
LogP:	5.051
LogD:	2.955
LogS:	-4.235
# Rotatable Bonds:	5
TPSA:	121.13
# H-Bond Aceptor:	7
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	11

MedChem Properties

QED Drug-Likeness Score:	0.172
Synthetic Accessibility Score:	3.741
Fsp3:	0.08
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	1
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.649
MDCK Permeability:	1.3932059118815232e-05
Pgp-inhibitor:	0.996
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.826
20% Bioavailability (F20%):	0.488
30% Bioavailability (F30%):	0.454

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.003
Plasma Protein Binding (PPB):	101.2122802734375%
Volume Distribution (VD):	0.338
Pgp-substrate:	1.2435728311538696%

ADMET: Metabolism

CYP1A2-inhibitor:	0.666
CYP1A2-substrate:	0.288
CYP2C19-inhibitor:	0.876
CYP2C19-substrate:	0.356
CYP2C9-inhibitor:	0.921
CYP2C9-substrate:	0.827
CYP2D6-inhibitor:	0.748
CYP2D6-substrate:	0.138
CYP3A4-inhibitor:	0.377
CYP3A4-substrate:	0.928

ADMET: Excretion

Clearance (CL):	0.265
Half-life (T1/2):	0.078

ADMET: Toxicity

hERG Blockers:	0.188
Human Hepatotoxicity (H-HT):	0.317
Drug-inuced Liver Injury (DILI):	0.964
AMES Toxicity:	0.014
Rat Oral Acute Toxicity:	0.829
Maximum Recommended Daily Dose:	0.934
Skin Sensitization:	0.201
Carcinogencity:	0.063
Eye Corrosion:	0.003
Eye Irritation:	0.44
Respiratory Toxicity:	0.025

Download Data

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

Natural Product: NPC489246

Natural Product ID:	NPC489246
*Common Name:**	DPAFYOFJIGKWIM-VWLOTQADSA-N
IUPAC Name:	n.a.
Synonyms:
Standard InCHIKey:	DPAFYOFJIGKWIM-VWLOTQADSA-N
Standard InCHI:	InChI=1S/C25H14Br4O7/c1-36-24(35)20-19(10-2-4-17(30)13(26)6-10)22(33)25(23(20)34,11-3-5-18(31)14(27)7-11)12-8-15(28)21(32)16(29)9-12/h2-9,30-32H,1H3/t25-/m0/s1
SMILES:	COC(=O)C1=C(c2ccc(c(c2)Br)O)C(=O)[C@](c2ccc(c(c2)Br)O)(c2cc(c(c(c2)Br)O)Br)C1=O
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:0000369] Diphenylmethanes

*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	4
MIC	6

Activity Type	# Activity
Cell Line	2
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	=	102000.0	nM	PMID[31967465]
NPT1087	Individual Protein	Isocitrate lyase	Candida albicans	IC50	=	47000.0	nM	PMID[31967465]
NPT111	Cell Line	K562	Homo sapiens	IC50	>	10000.0	nM	PMID[31967465]
NPT81	Cell Line	A549	Homo sapiens	IC50	>	10000.0	nM	PMID[31967465]
NPT16	Organism	Staphylococcus aureus	Staphylococcus aureus	MIC	=	32.0	ug.mL-1	PMID[31967465]
NPT175	Organism	Enterococcus faecalis	Enterococcus faecalis	MIC	>	128.0	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 NPC489246 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	354
0.1-0.2	1687
0.2-0.3	3941
0.3-0.4	11358
0.4-0.5	8614
0.5-0.6	10629
0.6-0.7	6036
0.7-0.8	53
0.8-0.85	10
0.85-0.9	11
0.9-0.95	0
0.95-1	4

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 NPC489246 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	317
0.1-0.2	991
0.2-0.3	1498
0.3-0.4	3064
0.4-0.5	2107
0.5-0.6	983
0.6-0.7	186
0.7-0.8	4
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