NPASS Compound

Natural Product: NPC116562

Natural Product ID	NPC116562
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3,5-Dibromo-4-Methoxyphenyl)Acetic Acid
IUPAC Name	2-(3,5-dibromo-4-methoxyphenyl)acetic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL394119
PubChem CID	10734734
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0002448] Benzenoids [CHEMONTID:0002341] Phenol ethers [CHEMONTID:0000138] Anisoles

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

Chemical Representations

Standard InCHIKey	PXJNCNLURDNKJO-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C9H8Br2O3/c1-14-9-6(10)2-5(3-7(9)11)4-8(12)13/h2-3H,4H2,1H3,(H,12,13)
SMILES	COc1c(cc(cc1Br)CC(=O)O)Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	321.88	Volume:	210.056 ? Van der Waals volume.
Dense:	1.532	LogP:	2.722 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.087 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.813 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	7.0
TPSA:	46.53 ? Topological Polar Surface Area.	H-Bond Acceptor:	3.0
H-Bond Donor:	1.0	Rings:	1.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.93	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.068	Fsp³:	0.222
MCE-18:	8.0 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.006	Fluc inhibitor:	0.001 ? 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:	0.315 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.915	Promiscuous compounds:	0.01

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.937	MDCK Permeability:	-4.646
Pgp-inhibitor:	0.003	Pgp-substrate:	0.046
PAMPA:	0.53 ? 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):	0.009
20% Bioavailability (F20%):	0.021	30% Bioavailability (F30%):	0.017
50% Bioavailability (F50%):	0.492

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.027	MRP1:	0.999
Plasma Protein Binding (PPB):	98.176%	Volume Distribution (VD):	-0.439
Fu:	1.303% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.912
OATP1B3 inhibitor:	0.929	BCRP inhibitor:	0.806
BSEP inhibitor:	0.871

ADMET: Metabolism

CYP1A2-inhibitor:	0.027	CYP1A2-substrate:	0.978
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.344
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.915	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	1.0
HLM stability:	0.016 ? 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):

1.421

Half-life (T1/2):

1.871

ADMET: Toxicity

hERG Blockers:	0.021	hERG Blockers (10um):	0.055
Human Hepatotoxicity (H-HT):	0.31	Drug-induced Liver Injury (DILI):	0.999
AMES Toxicity:	0.183	Rat Oral Acute Toxicity:	0.84
Maximum Recommended Daily Dose:	0.37	Skin Sensitization:	0.955
Carcinogencity:	0.348	Eye Corrosion:	0.985
Eye Irritation:	0.998	Respiratory Toxicity:	0.546
Drug-induced Neurotoxicity:	0.284	Ototoxicity:	0.266
Hematotoxicity:	0.111	Drug-induced Nephrotoxicity:	0.581
Genotoxicity:	0.965	RPMI-8226 Immunitoxicity:	0.031
A549 Cytotoxicity:	0.008	Hek293 Cytotoxicity:	0.021
BCF:	0.667 ? 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:	3.257 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.27 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.731 ? 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
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	Fruits	n.a.	n.a.	PMID[11141122]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO27935	Setosphaeria rostrata	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO12781	Schefflera heptaphylla	Species	Araliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7926	Ormosia macrocalyx	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11700	Melicope subunifoliolata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5012	Lobelia hassleri	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11175	Chromolaena collina	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5012	Lobelia hassleri	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5012	Lobelia hassleri	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO11700	Melicope subunifoliolata	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO5012	Lobelia hassleri	Species	Campanulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO13676	Zanthoxylum brachyacanthum	Species	Rutaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7926	Ormosia macrocalyx	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO7395	Tribulus terrestris	Species	Zygophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27935	Setosphaeria rostrata	Species	Pleosporaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11175	Chromolaena collina	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12781	Schefflera heptaphylla	Species	Araliaceae	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
Activity	3

Activity Type	# Activity
Individual protein	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT3825	Individual protein	Purinergic receptor P2Y1	Homo sapiens	Activity	<	37.5	%	PMID[17941622]
NPT3826	Individual protein	Purinergic receptor P2Y2	Homo sapiens	Activity	<	37.5	%	PMID[17941622]
NPT3829	Individual protein	Purinergic receptor P2Y11	Homo sapiens	Activity	<	37.5	%	PMID[17941622]

In vitro activity

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

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 NPC116562 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	32049
0.1-0.2	16750
0.2-0.3	995
0.3-0.4	55
0.4-0.5	6
0.5-0.6	2
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	Natural Product ID
0.6061	Remote Similarity	NPC234639
0.5385	Remote Similarity	NPC488998
0.5263	Remote Similarity	NPC322358

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC116562 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4069
0.1-0.2	4625
0.2-0.3	438
0.3-0.4	14
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
0.5238	Remote Similarity	NPD454	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