NPASS Compound

Natural Product: NPC603809

Natural Product ID	NPC603809
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MGPZBLVKGVLQIV-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1698399
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 26 0 0 0 0 0 0 0 0999 V2000 -3.1279 -1.7383 -0.0666 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4400 -0.4226 -0.0278 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1434 0.7206 -0.0023 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.4824 1.8887 0.0325 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1063 1.9566 0.0429 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3582 0.8064 0.0174 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0470 -0.3907 -0.0182 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0888 -1.3379 -0.0370 N 0 0 0 0 0 0 0 0 0 0 0 0 1.1359 -0.7863 -0.0149 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4103 -1.3130 -0.0207 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5354 -0.4957 0.0078 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4080 0.8758 0.0429 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9525 2.0192 0.0825 Br 0 0 0 0 0 0 0 0 0 0 0 0 2.1304 1.3945 0.0485 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0031 0.6040 0.0207 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4241 -1.9782 -1.1079 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9965 -1.7499 0.6376 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4599 -2.5565 0.2735 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0242 2.8325 0.0538 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5888 2.9124 0.0712 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3130 -2.3701 -0.0655 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5007 -2.4006 -0.0486 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5204 -0.9397 0.0023 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0038 2.4687 0.0758 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 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 12 14 1 0 14 15 2 0 7 2 1 0 15 9 1 0 15 6 1 0 1 16 1 0 1 17 1 0 1 18 1 0 4 19 1 0 5 20 1 0 8 21 1 0 10 22 1 0 11 23 1 0 14 24 1 0 M END

Standard InCHIKey	MGPZBLVKGVLQIV-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C12H9BrN2/c1-7-12-9(4-5-14-7)10-6-8(13)2-3-11(10)15-12/h2-6,15H,1H3
SMILES	Cc1nccc2c1[nH]c1ccc(Br)cc12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	259.99	Volume:	215.897 ? Van der Waals volume.
Dense:	1.204	LogP:	3.729 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.338 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.595 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	15.0
TPSA:	28.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	2.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	3.0

MedChem Properties

QED Drug-Likeness Score:	0.655	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.239	Fsp³:	0.083
MCE-18:	15.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.544	Fluc inhibitor:	0.253 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.657 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.594 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.052	Promiscuous compounds:	0.739

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.917	MDCK Permeability:	-4.626
Pgp-inhibitor:	0.174	Pgp-substrate:	0.018
PAMPA:	0.128 ? 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):	0.0
20% Bioavailability (F20%):	0.001	30% Bioavailability (F30%):	0.003
50% Bioavailability (F50%):	0.003

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.986	MRP1:	0.99
Plasma Protein Binding (PPB):	97.445%	Volume Distribution (VD):	0.196
Fu:	2.296% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.99
OATP1B3 inhibitor:	0.969	BCRP inhibitor:	0.001
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.917	CYP1A2-substrate:	0.081
CYP2C19-inhibitor:	0.927	CYP2C19-substrate:	0.154
CYP2C9-inhibitor:	0.98	CYP2C9-substrate:	0.994
CYP2D6-inhibitor:	0.989	CYP2D6-substrate:	0.676
CYP3A4-inhibitor:	0.957	CYP3A4-substrate:	0.052
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.542 ? 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):

8.295

Half-life (T1/2):

0.915

ADMET: Toxicity

hERG Blockers:	0.275	hERG Blockers (10um):	0.589
Human Hepatotoxicity (H-HT):	0.622	Drug-induced Liver Injury (DILI):	0.912
AMES Toxicity:	0.658	Rat Oral Acute Toxicity:	0.809
Maximum Recommended Daily Dose:	0.804	Skin Sensitization:	0.781
Carcinogencity:	0.805	Eye Corrosion:	0.018
Eye Irritation:	0.982	Respiratory Toxicity:	0.898
Drug-induced Neurotoxicity:	0.774	Ototoxicity:	0.457
Hematotoxicity:	0.501	Drug-induced Nephrotoxicity:	0.708
Genotoxicity:	0.815	RPMI-8226 Immunitoxicity:	0.093
A549 Cytotoxicity:	0.213	Hek293 Cytotoxicity:	0.337
BCF:	1.809 ? 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:	4.012 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.198 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.705 ? 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
NPO47380	Aglaophenia pluma	Species	Aglaopheniidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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
Potency	11
Activity	2

Activity Type	# Activity
Individual protein	5
Unchecked	5
Organism	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT154	Individual protein	Mothers against decapentaplegic homolog 3	Homo sapiens	Potency	n.a.	22387.2	nM	PubChem BioAssay data set
NPT101	Individual protein	Glucagon-like peptide 1 receptor	Homo sapiens	Potency	n.a.	14125.4	nM	PubChem BioAssay data set
NPT803	Individual protein	Flap endonuclease 1	Homo sapiens	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	23109.3	nM	PubChem BioAssay data set
NPT50	Individual protein	Tyrosyl-DNA phosphodiesterase 1	Homo sapiens	Potency	n.a.	29092.9	nM	PubChem BioAssay data set

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	28183.8	nM	PubChem BioAssay data set
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	Potency	n.a.	18526.0	nM	PubChem BioAssay data set
NPT29853	Organism	Bipolaris maydis	Bipolaris maydis	Activity	=	86.4	%	PMID[34954591]
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	12589.3	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	10000.0	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	3981.1	nM	PubChem BioAssay data set
NPT28438	Unchecked	Unchecked	n.a.	Potency	n.a.	23109.3	nM	PubChem BioAssay data set
NPT2705	Organism	Alternaria solani	Alternaria solani	Activity	=	73.7	%	PMID[34954591]

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 NPC603809 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	44882
0.1-0.2	4596
0.2-0.3	285
0.3-0.4	53
0.4-0.5	27
0.5-0.6	11
0.6-0.7	4
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
0.6444	Remote Similarity	NPC179787
0.6415	Remote Similarity	NPC97343
0.6087	Remote Similarity	NPC609483
0.6	Remote Similarity	NPC470505
0.569	Remote Similarity	NPC470503
0.569	Remote Similarity	NPC279189
0.569	Remote Similarity	NPC26641
0.5686	Remote Similarity	NPC176538
0.56	Remote Similarity	NPC175899
0.541	Remote Similarity	NPC470501
0.541	Remote Similarity	NPC162002
0.5385	Remote Similarity	NPC606585
0.5185	Remote Similarity	NPC292958
0.5094	Remote Similarity	NPC232727
0.5094	Remote Similarity	NPC274229

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC603809 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6153
0.1-0.2	2928
0.2-0.3	68
0.3-0.4	1
0.4-0.5	0
0.5-0.6	0
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
		NPD

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