NPASS Compound

Natural Product: NPC97157

Natural Product ID	NPC97157
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	3,4,6-Tribromo-2-(2,4-Dibromophenoxy)Phenol
IUPAC Name	3,4,6-tribromo-2-(2,4-dibromophenoxy)phenol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL186098
PubChem CID	11093078
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002279] Benzene and substituted derivatives [CHEMONTID:0004155] Diphenylethers [CHEMONTID:0001845] Bromodiphenyl ethers

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 24 25 0 0 0 0 0 0 0 0999 V2000 -5.2688 0.9380 1.4111 Br 0 0 0 0 0 0 0 0 0 0 0 0 -3.6183 0.3906 0.6887 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4027 0.7910 1.1822 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2066 0.3819 0.6429 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2605 -0.4791 -0.4552 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4644 -0.9087 -0.9862 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6322 -0.4723 -0.4124 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4526 -2.0906 -2.4948 Br 0 0 0 0 0 0 0 0 0 0 0 0 -0.1042 -0.9290 -1.0460 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1107 -0.5325 -0.5573 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7846 0.6071 -0.9997 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1868 1.3763 -1.9883 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0131 0.9720 -0.4777 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8800 2.5483 -1.1325 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.6130 0.2227 0.4968 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9400 -0.9156 0.9388 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7213 -1.2901 0.4306 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8984 -2.8661 1.1140 Br 0 0 0 0 0 0 0 0 0 0 0 0 3.7377 -1.9863 2.2923 Br 0 0 0 0 0 0 0 0 0 0 0 0 -2.3696 1.4640 2.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2386 0.7000 1.0351 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5783 -0.8147 -0.8359 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1359 2.3821 -1.7913 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5753 0.5108 0.9040 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 6 8 1 0 5 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 11 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 16 19 1 0 7 2 1 0 17 10 1 0 3 20 1 0 4 21 1 0 7 22 1 0 12 23 1 0 15 24 1 0 M END

Standard InCHIKey	FAGFPLJEMPQMRV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H5Br5O2/c13-5-1-2-9(6(14)3-5)19-12-10(17)7(15)4-8(16)11(12)18/h1-4,18H
SMILES	Brc1ccc(c(c1)Br)Oc1c(O)c(Br)cc(c1Br)Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	575.62	Volume:	297.175 ? Van der Waals volume.
Dense:	1.937	LogP:	5.159 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.438 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-6.056 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	12.0
TPSA:	29.46 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.388	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.636	Fsp³:	0.0
MCE-18:	14.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.925	Fluc inhibitor:	0.618 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.011 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.433 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.997	Promiscuous compounds:	0.391

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.037	MDCK Permeability:	-4.733
Pgp-inhibitor:	0.857	Pgp-substrate:	0.0
PAMPA:	0.549 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.095
20% Bioavailability (F20%):	0.002	30% Bioavailability (F30%):	0.07
50% Bioavailability (F50%):	0.014

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.646	MRP1:	0.965
Plasma Protein Binding (PPB):	97.137%	Volume Distribution (VD):	0.048
Fu:	1.45% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.962
OATP1B3 inhibitor:	0.979	BCRP inhibitor:	0.056
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.016
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.258
CYP3A4-inhibitor:	0.002	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.009 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

4.689

Half-life (T1/2):

1.741

ADMET: Toxicity

hERG Blockers:	0.131	hERG Blockers (10um):	0.797
Human Hepatotoxicity (H-HT):	0.174	Drug-induced Liver Injury (DILI):	0.998
AMES Toxicity:	0.158	Rat Oral Acute Toxicity:	0.868
Maximum Recommended Daily Dose:	0.993	Skin Sensitization:	0.995
Carcinogencity:	0.824	Eye Corrosion:	0.997
Eye Irritation:	1.0	Respiratory Toxicity:	0.691
Drug-induced Neurotoxicity:	0.801	Ototoxicity:	0.059
Hematotoxicity:	0.006	Drug-induced Nephrotoxicity:	0.092
Genotoxicity:	0.99	RPMI-8226 Immunitoxicity:	0.054
A549 Cytotoxicity:	0.489	Hek293 Cytotoxicity:	0.494
BCF:	2.46 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	5.781 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.414 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	6.393 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[11374954]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[15921404]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[1593283]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18198840]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	at 1020 m depth from Chuuk Atoll, Federated States of Micronesia	n.a.	PMID[18824352]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[20230038]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26551342]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[26863083]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[27336796]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[32243140]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	Indo-Pacific	n.a.	PMID[7494145]
NPO32617	dysidea sp.	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[9748373]

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	Organism Name	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
IZ	6

Activity Type	# Activity
Individual protein	2
Cell line	1
Organism	6
Others	1

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT1119	Individual protein	Arachidonate 12-lipoxygenase	Homo sapiens	IC50	=	6000.0	nM	PMID[16252912]
NPT792	Individual protein	Arachidonate 15-lipoxygenase	Homo sapiens	IC50	=	5000.0	nM	PMID[16309322]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT83	Cell line	MCF7	Homo sapiens	IC50	=	8730.0	nM	PubChem BioAssay data set
NPT447	Organism	Streptomyces	Streptomyces	IZ	=	12.0	mm	PMID[22742732]
NPT447	Organism	Streptomyces	Streptomyces	IZ	=	3.0	mm	PMID[22742732]
NPT447	Organism	Streptomyces	Streptomyces	IZ	=	2.0	mm	PMID[12109913]
NPT447	Organism	Streptomyces	Streptomyces	IZ	=	15.0	mm	PMID[14640526]
NPT447	Organism	Streptomyces	Streptomyces	IZ	=	13.0	mm	DrugMatrix in vivo data: Pathology
NPT2	Others	Unspecified	n.a.	IC50	=	9000.0	nM	PMID[26225905]

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

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 toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC97157 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	36535
0.1-0.2	13150
0.2-0.3	121
0.3-0.4	25
0.4-0.5	11
0.5-0.6	8
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.7179	Intermediate Similarity	NPC47769
0.6667	Remote Similarity	NPC159866
0.6429	Remote Similarity	NPC175520
0.6136	Remote Similarity	NPC299939
0.6098	Remote Similarity	NPC86007
0.6047	Remote Similarity	NPC44270
0.5814	Remote Similarity	NPC603923
0.5682	Remote Similarity	NPC226737
0.5652	Remote Similarity	NPC64130
0.5556	Remote Similarity	NPC153580
0.5556	Remote Similarity	NPC319933
0.5417	Remote Similarity	NPC178301
0.5349	Remote Similarity	NPC205213
0.5349	Remote Similarity	NPC235370

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC97157 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5963
0.1-0.2	3092
0.2-0.3	87
0.3-0.4	4
0.4-0.5	3
0.5-0.6	1
0.6-0.7	0
0.7-0.8	0
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
0.5349	Remote Similarity	NPD915	Phase 4

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by 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