NPASS Compound

Natural Product: NPC18216

Natural Product ID	NPC18216
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FLJICWZSHAGHJX-UHFFFAOYSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0001819] Isoindoles and derivatives [CHEMONTID:0002496] Isoindolines [CHEMONTID:0001820] Isoindolones

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 30 33 0 0 0 0 0 0 0 0999 V2000 -3.8313 -0.0407 -1.6463 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7874 0.1661 -0.6830 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4076 0.3648 0.6269 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0656 0.3474 0.9194 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0764 0.1386 -0.0463 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4827 -0.0549 -1.3328 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8095 0.1870 0.6212 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4134 0.0523 0.1713 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0356 -0.1893 -1.1009 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5024 -0.3451 -2.1978 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5227 -0.2395 -0.9627 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5351 -0.4394 -1.8678 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8460 -0.4344 -1.4495 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0958 -0.2250 -0.1130 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0795 -0.0225 0.8062 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7640 -0.0311 0.3647 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5551 0.1461 1.0747 N 0 0 0 0 0 0 0 0 0 0 0 0 -1.1243 0.4359 2.0281 N 0 0 0 0 0 0 0 0 0 0 0 0 -2.3743 0.5260 2.2010 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9708 0.7600 3.4345 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1233 -0.1973 -2.6771 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8400 0.1776 -0.9255 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1286 0.5314 1.4178 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7496 -0.2181 -2.0995 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2855 -0.6011 -2.9168 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6189 -0.5896 -2.1561 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1021 -0.2083 0.2855 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2902 0.1425 1.8631 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5009 0.3189 2.1004 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3759 0.8688 4.2603 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 3 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 7 18 1 0 18 19 2 0 19 20 1 0 6 1 1 0 17 8 1 0 19 4 1 0 16 11 1 0 1 21 1 0 2 22 1 0 3 23 1 0 6 24 1 0 12 25 1 0 13 26 1 0 14 27 1 0 15 28 1 0 17 29 1 0 20 30 1 0 M END

Standard InCHIKey	FLJICWZSHAGHJX-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C16H10N2O2/c19-15-11-7-3-4-8-12(11)17-14(15)13-9-5-1-2-6-10(9)16(20)18-13/h1-8,17H,(H,18,20)
SMILES	c1ccc2c(c1)C(=C1C(=O)c3ccccc3N1)N=C2O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	262.07	Volume:	266.912 ? Van der Waals volume.
Dense:	0.982	LogP:	2.545 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.128 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.373 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	0.0	Rigid Bonds:	22.0
TPSA:	61.69 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	2.0	Rings:	4.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.717	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.691	Fsp³:	0.0
MCE-18:	40.0 ? 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:	1
Colloidal aggregators:	0.746	Fluc inhibitor:	0.929 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.406 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.294 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.092	Promiscuous compounds:	0.47

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.387	MDCK Permeability:	-4.65
Pgp-inhibitor:	0.954	Pgp-substrate:	0.012
PAMPA:	0.734 ? 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):	0.292
20% Bioavailability (F20%):	0.002	30% Bioavailability (F30%):	0.142
50% Bioavailability (F50%):	0.305

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.208
Plasma Protein Binding (PPB):	97.756%	Volume Distribution (VD):	-0.205
Fu:	1.621% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.866
OATP1B3 inhibitor:	0.965	BCRP inhibitor:	0.001
BSEP inhibitor:	0.67

ADMET: Metabolism

CYP1A2-inhibitor:	0.358	CYP1A2-substrate:	0.972
CYP2C19-inhibitor:	0.002	CYP2C19-substrate:	0.981
CYP2C9-inhibitor:	0.025	CYP2C9-substrate:	0.852
CYP2D6-inhibitor:	0.061	CYP2D6-substrate:	0.788
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.159
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.951
HLM stability:	0.963 ? 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):

0.326

Half-life (T1/2):

1.446

ADMET: Toxicity

hERG Blockers:	0.038	hERG Blockers (10um):	0.195
Human Hepatotoxicity (H-HT):	0.973	Drug-induced Liver Injury (DILI):	0.996
AMES Toxicity:	0.858	Rat Oral Acute Toxicity:	0.482
Maximum Recommended Daily Dose:	0.596	Skin Sensitization:	0.953
Carcinogencity:	0.91	Eye Corrosion:	0.0
Eye Irritation:	0.89	Respiratory Toxicity:	0.566
Drug-induced Neurotoxicity:	0.802	Ototoxicity:	0.43
Hematotoxicity:	0.739	Drug-induced Nephrotoxicity:	0.907
Genotoxicity:	0.991	RPMI-8226 Immunitoxicity:	0.024
A549 Cytotoxicity:	0.014	Hek293 Cytotoxicity:	0.197
BCF:	1.022 ? 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:	3.745 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.52 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.221 ? 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
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1016/j.jarmap.2018.11.004]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11678654]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15787451]
NPO626	Indigofera tinctoria	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16644212]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	Roots	Anhui, China	n.a.	PMID[22694318]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	Roots	n.a.	n.a.	PMID[32004936]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[39053741]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4582	Baphicacanthus cusia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4582	Baphicacanthus cusia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO5812	Indigo naturalis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO626	Indigofera tinctoria	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30651	Folium polygoni	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO626	Indigofera tinctoria	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8277	Folium polygoni tinctorii	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5812	Indigo naturalis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO4582	Baphicacanthus cusia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO31573	Polygonum tinctorium	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO31050	Isatis indigotica	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO4582	Baphicacanthus cusia	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO4554	Isatis tinctoria	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO9069	Persicaria tinctoria	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO626	Indigofera tinctoria	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4582	Baphicacanthus cusia	Species	Acanthaceae	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

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 NPC18216 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	38451
0.1-0.2	11253
0.2-0.3	145
0.3-0.4	9
0.4-0.5	0
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	Natural Product ID
0.5435	Remote Similarity	NPC209389

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC18216 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4609
0.1-0.2	4463
0.2-0.3	77
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