NPASS Compound

Natural Product: NPC30521

Natural Product ID	NPC30521
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KQYZOOUJAWUDAP-WCBMZHEXSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	10068433
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002490] Azolines [CHEMONTID:0002211] Isoxazolines

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 -4.6637 0.6552 0.1351 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6798 -0.0682 0.8440 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3548 -0.1464 0.4006 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9340 -1.1346 -0.3548 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5547 -1.2728 -0.8525 C 0 0 1 0 0 0 0 0 0 0 0 0 0.3858 -0.1960 -0.4445 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.1948 0.8620 0.4028 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4278 0.9022 0.7945 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0936 2.3371 1.9076 Br 0 0 0 0 0 0 0 0 0 0 0 0 1.5878 -0.7389 0.3185 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6510 0.1979 -0.1144 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2759 0.7790 -1.2044 N 0 0 0 0 0 0 0 0 0 0 0 0 1.0281 0.3349 -1.5899 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8987 0.4170 0.5779 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1384 -0.2138 1.6281 O 0 0 0 0 0 0 0 0 0 0 0 0 4.8658 1.3314 0.0994 N 0 0 0 0 0 0 0 0 0 0 0 0 -0.0681 -2.5306 -0.4335 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1842 -2.4946 -0.8513 Br 0 0 0 0 0 0 0 0 0 0 0 0 -5.6112 0.5562 0.6939 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7477 0.3355 -0.9230 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3778 1.7340 0.1140 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6430 -1.2973 -1.9799 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4698 1.6559 0.7120 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4023 -0.6330 1.4014 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8057 -1.7865 0.0355 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7346 0.9623 -0.3397 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7639 2.3665 0.1586 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5276 -2.9145 -1.1361 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 1 0 6 7 1 0 7 8 2 0 8 9 1 0 6 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 11 14 1 0 14 15 2 0 14 16 1 0 5 17 1 0 4 18 1 0 8 3 1 0 6 13 1 6 1 19 1 0 1 20 1 0 1 21 1 0 5 22 1 6 7 23 1 0 10 24 1 0 10 25 1 0 16 26 1 0 16 27 1 0 17 28 1 0 M END

Standard InCHIKey	KQYZOOUJAWUDAP-WCBMZHEXSA-N
Standard InCHI	InChI=1S/C10H10Br2N2O4/c1-17-7-4(11)2-10(8(15)6(7)12)3-5(9(13)16)14-18-10/h2,8,15H,3H2,1H3,(H2,13,16)/t8-,10+/m0/s1
SMILES	COC1=C([C@@H]([C@@]2(C=C1Br)CC(=NO2)C(=O)N)O)Br

Calculated Properties

Physi-Chem Properties

Molecular Weight:	379.9	Volume:	249.579 ? Van der Waals volume.
Dense:	1.522	LogP:	1.122 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.238 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.828 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	2.0	Rigid Bonds:	12.0
TPSA:	94.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	3.0	Rings:	2.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.742	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.796	Fsp³:	0.4
MCE-18:	51.429 ? 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:	0.283	Fluc inhibitor:	0.03 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.065 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.21 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.376	Promiscuous compounds:	0.123

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.928	MDCK Permeability:	-4.73
Pgp-inhibitor:	0.006	Pgp-substrate:	0.549
PAMPA:	0.182 ? 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%):	0.002	30% Bioavailability (F30%):	0.007
50% Bioavailability (F50%):	0.208

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.985	MRP1:	0.997
Plasma Protein Binding (PPB):	90.522%	Volume Distribution (VD):	0.214
Fu:	6.816% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.967
OATP1B3 inhibitor:	0.952	BCRP inhibitor:	0.029
BSEP inhibitor:	0.037

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.008
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.158
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.05
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.926
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.806
HLM stability:	0.587 ? 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):

0.627

Half-life (T1/2):

3.205

ADMET: Toxicity

hERG Blockers:	0.065	hERG Blockers (10um):	0.328
Human Hepatotoxicity (H-HT):	0.81	Drug-induced Liver Injury (DILI):	0.988
AMES Toxicity:	0.97	Rat Oral Acute Toxicity:	0.914
Maximum Recommended Daily Dose:	0.861	Skin Sensitization:	0.997
Carcinogencity:	0.982	Eye Corrosion:	0.062
Eye Irritation:	0.975	Respiratory Toxicity:	0.925
Drug-induced Neurotoxicity:	0.88	Ototoxicity:	0.361
Hematotoxicity:	0.246	Drug-induced Nephrotoxicity:	0.453
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.186
A549 Cytotoxicity:	0.185	Hek293 Cytotoxicity:	0.484
BCF:	0.51 ? 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:	3.151 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.324 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.49 ? 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
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	Taiwanese gorgonian coral	n.a.	PMID[12088433]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	Taiwanese Gorgonian coral	n.a.	PMID[12141868]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[16124781]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	PMID[18290631]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO11745	Subergorgia suberosa	Species	Subergorgiidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO11870	Rhododendron arboreum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO12594	Hybanthus enneaspermus	Species	Violaceae	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
Ratio IC50	2

Activity Type	# Activity
Individual protein	4
Unchecked	2

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT67	Individual protein	Cholinesterase	Equus caballus	IC50	=	15400.0	nM	PMID[36095307]
NPT66	Individual protein	Acetylcholinesterase	Electrophorus electricus	IC50	=	3320.0	nM	PMID[36095307]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT28438	Unchecked	Unchecked	n.a.	Ratio IC50	=	4.6	n.a.	PMID[36095307]

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 NPC30521 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	22933
0.1-0.2	26637
0.2-0.3	232
0.3-0.4	10
0.4-0.5	16
0.5-0.6	18
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
0.7255	Intermediate Similarity	NPC1702
0.6981	Remote Similarity	NPC158672
0.6607	Remote Similarity	NPC487917
0.6066	Remote Similarity	NPC473262
0.6066	Remote Similarity	NPC202166
0.6032	Remote Similarity	NPC313173
0.5873	Remote Similarity	NPC145149
0.5873	Remote Similarity	NPC473261
0.5873	Remote Similarity	NPC300912
0.5758	Remote Similarity	NPC66855
0.5692	Remote Similarity	NPC81079
0.5692	Remote Similarity	NPC304257
0.5692	Remote Similarity	NPC260270
0.5606	Remote Similarity	NPC487872
0.5606	Remote Similarity	NPC470886
0.5606	Remote Similarity	NPC600759
0.5606	Remote Similarity	NPC608122
0.5522	Remote Similarity	NPC181086
0.5441	Remote Similarity	NPC201900
0.5441	Remote Similarity	NPC130714
0.5362	Remote Similarity	NPC487873
0.5286	Remote Similarity	NPC477220
0.5286	Remote Similarity	NPC608121
0.5068	Remote Similarity	NPC487915

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC30521 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5800
0.1-0.2	3339
0.2-0.3	11
0.3-0.4	0
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