NPASS Compound

Natural Product: NPC170824

Natural Product ID	NPC170824
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2,4-Dibromo-6-(2,4-Dibromo-6-Methoxyphenoxy)Phenol
IUPAC Name	2,4-dibromo-6-(2,4-dibromo-6-methoxyphenoxy)phenol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL186099
PubChem CID	10554258
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 28 29 0 0 0 0 0 0 0 0999 V2000 -2.0479 2.6360 0.0969 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1980 1.5346 0.4048 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.7068 0.2490 0.2861 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0039 0.0188 -0.1194 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4919 -1.2629 -0.2316 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6577 -2.3066 0.0701 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3438 -2.0633 0.4811 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8406 -0.7961 0.5972 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4235 -0.5609 0.9944 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5472 -0.1912 0.3685 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1786 0.9817 0.8043 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3216 1.4769 0.2631 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8943 0.7850 -0.7760 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3125 -0.3756 -1.2430 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1326 -0.8589 -0.6621 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6466 -2.0264 -1.2171 O 0 0 0 0 0 0 0 0 0 0 0 0 4.1318 -1.3167 -2.6896 Br 0 0 0 0 0 0 0 0 0 0 0 0 4.1649 3.0784 0.8736 Br 0 0 0 0 0 0 0 0 0 0 0 0 -0.3409 -3.6399 0.9172 Br 0 0 0 0 0 0 0 0 0 0 0 0 -5.2926 -1.5057 -0.7980 Br 0 0 0 0 0 0 0 0 0 0 0 0 -2.8627 2.7000 0.8499 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4674 3.5781 0.0333 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5646 2.4812 -0.8942 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6427 0.8371 -0.3504 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0569 -3.3224 -0.0228 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7373 1.5460 1.6303 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8136 1.1725 -1.2198 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2140 -2.8490 -1.3798 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 14 17 1 0 12 18 1 0 7 19 1 0 5 20 1 0 8 3 1 0 15 10 1 0 1 21 1 0 1 22 1 0 1 23 1 0 4 24 1 0 6 25 1 0 11 26 1 0 13 27 1 0 16 28 1 0 M END

Standard InCHIKey	ZMXOEWVGOVDWHT-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C13H8Br4O3/c1-19-11-5-7(15)3-9(17)13(11)20-10-4-6(14)2-8(16)12(10)18/h2-5,18H,1H3
SMILES	COc1cc(cc(c1Oc1cc(cc(c1O)Br)Br)Br)Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	527.72	Volume:	303.978 ? Van der Waals volume.
Dense:	1.736	LogP:	4.614 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.33 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.737 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	12.0
TPSA:	38.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.509	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.435	Fsp³:	0.077
MCE-18:	14.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Accepted
Golden Triangle Rule:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.927	Fluc inhibitor:	0.052 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.022 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.512 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.988	Promiscuous compounds:	0.32

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.054	MDCK Permeability:	-4.748
Pgp-inhibitor:	0.58	Pgp-substrate:	0.003
PAMPA:	0.19 ? 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):	0.018
20% Bioavailability (F20%):	0.004	30% Bioavailability (F30%):	0.026
50% Bioavailability (F50%):	0.005

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.529	MRP1:	0.987
Plasma Protein Binding (PPB):	97.219%	Volume Distribution (VD):	0.02
Fu:	1.327% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.869
OATP1B3 inhibitor:	0.786	BCRP inhibitor:	0.081
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.042
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.022
CYP3A4-inhibitor:	0.014	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.048 ? 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):

5.003

Half-life (T1/2):

2.131

ADMET: Toxicity

hERG Blockers:	0.122	hERG Blockers (10um):	0.723
Human Hepatotoxicity (H-HT):	0.254	Drug-induced Liver Injury (DILI):	0.986
AMES Toxicity:	0.161	Rat Oral Acute Toxicity:	0.778
Maximum Recommended Daily Dose:	0.958	Skin Sensitization:	0.979
Carcinogencity:	0.792	Eye Corrosion:	0.924
Eye Irritation:	0.997	Respiratory Toxicity:	0.568
Drug-induced Neurotoxicity:	0.705	Ototoxicity:	0.091
Hematotoxicity:	0.026	Drug-induced Nephrotoxicity:	0.118
Genotoxicity:	0.928	RPMI-8226 Immunitoxicity:	0.062
A549 Cytotoxicity:	0.248	Hek293 Cytotoxicity:	0.404
BCF:	2.283 ? 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:	5.36 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.065 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.559 ? 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]
NPO24471	Dysidea dendyi	Species	Dysideidae	Eukaryota	n.a.	Australian	n.a.	PMID[11434317]
NPO24471	Dysidea dendyi	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	PMID[12193037]
NPO8481	Phyllospongia dendyi	Species	Thorectidae	Eukaryota	n.a.	Palau	n.a.	PMID[15043436]
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]
NPO8481	Phyllospongia dendyi	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO24471	Dysidea dendyi	Species	Dysideidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8481	Phyllospongia dendyi	Species	Thorectidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO24471	Dysidea dendyi	Species	Dysideidae	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	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

Activity Type	# Activity
Individual protein	2
Others	2

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	=	12000.0	nM	PMID[18663019]
NPT792	Individual protein	Arachidonate 15-lipoxygenase	Homo sapiens	IC50	=	10000.0	nM	PMID[19995673]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT2	Others	Unspecified	n.a.	IC50	>	100000.0	nM	PMID[11473426]
NPT2	Others	Unspecified	n.a.	IC50	=	4700.0	nM	PMID[23545138]

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 NPC170824 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	32196
0.1-0.2	17042
0.2-0.3	570
0.3-0.4	28
0.4-0.5	9
0.5-0.6	8
0.6-0.7	2
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
0.75	Intermediate Similarity	NPC88733
0.7111	Intermediate Similarity	NPC230013
0.6739	Remote Similarity	NPC81149
0.6667	Remote Similarity	NPC68350
0.5778	Remote Similarity	NPC44270
0.5778	Remote Similarity	NPC104124
0.5714	Remote Similarity	NPC483502
0.5682	Remote Similarity	NPC221301
0.5556	Remote Similarity	NPC196371
0.5556	Remote Similarity	NPC601831
0.5319	Remote Similarity	NPC40302
0.5217	Remote Similarity	NPC603923

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC170824 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5115
0.1-0.2	3947
0.2-0.3	85
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6316	Remote Similarity	NPD911	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