NPASS Compound

Natural Product: NPC326816

Natural Product ID	NPC326816
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	LKYWXXAVLLVJAS-UHFFFAOYSA-M
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	45479415
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000211] Indoles and derivatives [CHEMONTID:0001290] Indolyl carboxylic acids and derivatives

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 -2.8681 -1.2466 0.6698 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4973 -0.5767 -0.3433 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8748 0.3456 -1.1476 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5452 0.5945 -0.9015 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8519 -0.0537 0.1121 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5269 -0.9730 0.8886 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4522 0.3951 0.1650 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5272 1.3281 -0.8458 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6677 1.4303 -1.4644 N 0 0 0 0 0 0 0 0 0 0 0 0 1.5376 -0.0159 1.0791 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8776 -0.0229 0.4650 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7446 0.7896 0.9593 N 0 0 0 0 0 0 0 0 0 0 0 0 3.2545 -0.8686 -0.6366 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4344 -0.8005 -1.1293 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4161 -1.7857 -1.2302 O 0 0 0 0 0 1 0 0 0 0 0 0 -3.3314 -1.9770 1.3211 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5419 -0.7770 -0.5224 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4500 0.8160 -1.9152 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9837 -1.4790 1.6748 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4262 1.8926 -1.0881 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8888 2.0708 -2.2780 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2541 -1.0717 1.3902 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5275 0.5526 2.0312 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5759 1.4331 1.7346 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 2 0 8 9 1 0 7 10 1 0 10 11 1 0 11 12 2 3 11 13 1 0 13 14 2 0 13 15 1 0 6 1 1 0 9 4 1 0 1 16 1 0 2 17 1 0 3 18 1 0 6 19 1 0 8 20 1 0 9 21 1 0 10 22 1 0 10 23 1 0 12 24 1 0 M CHG 1 15 -1 M END

Standard InCHIKey	LKYWXXAVLLVJAS-UHFFFAOYSA-M
Standard InCHI	InChI=1S/C11H10N2O2/c12-9(11(14)15)5-7-6-13-10-4-2-1-3-8(7)10/h1-4,6,12-13H,5H2,(H,14,15)/p-1
SMILES	C1=CC=C2C(=C1)C(=CN2)CC(=N)C(=O)[O-]

Calculated Properties

Physi-Chem Properties

Molecular Weight:	202.07	Volume:	205.455 ? Van der Waals volume.
Dense:	0.984	LogP:	0.371 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.961 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.74 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	12.0
TPSA:	76.94 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.664	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.372	Fsp³:	0.091
MCE-18:	11.0 ? 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:	0.015	Fluc inhibitor:	0.015 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.199 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.139 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.011	Promiscuous compounds:	0.429

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.403	MDCK Permeability:	-4.792
Pgp-inhibitor:	0.0	Pgp-substrate:	0.011
PAMPA:	0.896 ? 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):	0.04
20% Bioavailability (F20%):	0.518	30% Bioavailability (F30%):	0.973
50% Bioavailability (F50%):	0.966

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.017	MRP1:	0.362
Plasma Protein Binding (PPB):	69.144%	Volume Distribution (VD):	-0.758
Fu:	28.545% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.98
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.002
BSEP inhibitor:	0.287

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.001
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.312	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.006	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.003	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.447
HLM stability:	0.018 ? 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):

1.583

Half-life (T1/2):

1.781

ADMET: Toxicity

hERG Blockers:	0.081	hERG Blockers (10um):	0.249
Human Hepatotoxicity (H-HT):	0.542	Drug-induced Liver Injury (DILI):	0.602
AMES Toxicity:	0.333	Rat Oral Acute Toxicity:	0.707
Maximum Recommended Daily Dose:	0.374	Skin Sensitization:	0.858
Carcinogencity:	0.468	Eye Corrosion:	0.001
Eye Irritation:	0.684	Respiratory Toxicity:	0.902
Drug-induced Neurotoxicity:	0.408	Ototoxicity:	0.308
Hematotoxicity:	0.248	Drug-induced Nephrotoxicity:	0.325
Genotoxicity:	0.952	RPMI-8226 Immunitoxicity:	0.012
A549 Cytotoxicity:	0.013	Hek293 Cytotoxicity:	0.048
BCF:	0.17 ? 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:	2.871 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.002 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.343 ? 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
NPO2082	Chromobacterium violaceum	Species	Chromobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[17176066]
NPO2082	Chromobacterium violaceum	Species	Chromobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[20490411]
NPO2082	Chromobacterium violaceum	Species	Chromobacteriaceae	Bacteria	n.a.	n.a.	n.a.	PMID[21779844]
NPO2082	Chromobacterium violaceum	Species	Chromobacteriaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO2082	Chromobacterium violaceum	Species	Chromobacteriaceae	Bacteria	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

Molecular-level activity

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

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 NPC326816 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	38887
0.1-0.2	9579
0.2-0.3	1015
0.3-0.4	250
0.4-0.5	95
0.5-0.6	24
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
0.6429	Remote Similarity	NPC601214
0.6078	Remote Similarity	NPC14113
0.6078	Remote Similarity	NPC145885
0.6078	Remote Similarity	NPC84827
0.6	Remote Similarity	NPC315555
0.587	Remote Similarity	NPC230869
0.587	Remote Similarity	NPC279081
0.58	Remote Similarity	NPC78020
0.5714	Remote Similarity	NPC605863
0.5686	Remote Similarity	NPC55772
0.5652	Remote Similarity	NPC96102
0.5577	Remote Similarity	NPC149155
0.5577	Remote Similarity	NPC203468
0.5577	Remote Similarity	NPC110500
0.5577	Remote Similarity	NPC605329
0.551	Remote Similarity	NPC73767
0.5472	Remote Similarity	NPC480318
0.5417	Remote Similarity	NPC29886
0.54	Remote Similarity	NPC310665
0.537	Remote Similarity	NPC248041
0.5306	Remote Similarity	NPC84911
0.5273	Remote Similarity	NPC480317
0.5273	Remote Similarity	NPC480316
0.5217	Remote Similarity	NPC102423
0.5185	Remote Similarity	NPC480551
0.5179	Remote Similarity	NPC267885
0.5094	Remote Similarity	NPC59269
0.5094	Remote Similarity	NPC600736
0.5091	Remote Similarity	NPC489095

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC326816 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5299
0.1-0.2	3665
0.2-0.3	131
0.3-0.4	42
0.4-0.5	9
0.5-0.6	4
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
0.5652	Remote Similarity	NPD198	Clinical (unspecified phase)
0.5577	Remote Similarity	NPD482	Phase 4
0.5472	Remote Similarity	NPD749	Clinical (unspecified phase)
0.5098	Remote Similarity	NPD786	Pre-clinical

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