NPASS Compound

Natural Product: NPC537076

Natural Product ID	NPC537076
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	tetrahydrojusticidin B
IUPAC Name	(3~{a}~{R},4~{R})-4-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-3~{a},4,9,9~{a}-tetrahydro-1~{H}-benzo[f]isobenzofuran-3-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001510] Lignan lactones

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 47 51 0 0 0 0 0 0 0 0999 V2000 -5.2504 0.2773 -1.7061 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2603 -0.7061 -1.7058 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0787 -0.5992 -0.9882 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8465 0.5371 -0.2224 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6904 0.6917 0.5078 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7472 -0.3005 0.4767 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9789 -1.4562 -0.2995 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1373 -1.6030 -1.0264 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3927 -2.7347 -1.8022 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.4249 -3.7824 -1.8503 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5180 -0.1699 1.2430 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6732 -0.0661 0.3122 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7266 0.9686 -0.5906 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8064 1.0550 -1.4414 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8358 0.1396 -1.4193 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0157 0.0117 -2.1632 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8852 -0.8983 -1.4964 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9571 -1.6593 -0.7258 O 0 0 0 0 0 0 0 0 0 0 0 0 3.8047 -0.9172 -0.5144 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7114 -0.9724 0.3202 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4568 0.7727 2.3530 C 0 0 1 0 0 0 0 0 0 0 0 0 1.2547 1.9887 2.3188 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2299 2.4050 1.6584 O 0 0 0 0 0 0 0 0 0 0 0 0 0.7062 2.8288 3.3132 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6238 2.4626 3.6018 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9374 1.3408 2.6600 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4393 1.8957 1.3326 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9588 0.0537 -2.5375 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8285 0.1601 -0.7464 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8084 1.2768 -1.7819 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5632 1.3473 -0.1676 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2260 -2.2284 -0.3129 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5109 -3.4464 -2.4117 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1502 -4.0929 -0.8331 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8512 -4.6143 -2.4548 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6598 -1.2132 1.7098 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9175 1.7244 -0.6448 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8201 1.8809 -2.1409 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4786 -1.5077 -2.1784 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5252 -0.3198 -0.7674 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6858 -1.8123 1.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7214 0.2564 3.3443 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3218 3.3143 3.3958 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7418 2.1091 4.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5993 0.5733 3.0686 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3788 2.4782 1.5068 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6436 2.5505 0.9393 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 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 6 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 2 0 11 21 1 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 8 3 1 0 20 12 1 0 26 21 1 0 27 5 1 0 19 15 1 0 1 28 1 0 1 29 1 0 1 30 1 0 4 31 1 0 7 32 1 0 10 33 1 0 10 34 1 0 10 35 1 0 11 36 1 1 13 37 1 0 14 38 1 0 17 39 1 0 17 40 1 0 20 41 1 0 21 42 1 1 25 43 1 0 25 44 1 0 26 45 1 0 27 46 1 0 27 47 1 0 M END

Standard InCHIKey	LAFREGHROJJWDK-CFNCIARGSA-N
Standard InCHI	InChI=1S/C21H20O6/c1-23-16-7-12-5-13-9-25-21(22)20(13)19(14(12)8-17(16)24-2)11-3-4-15-18(6-11)27-10-26-15/h3-4,6-8,13,19-20H,5,9-10H2,1-2H3/t13?,19-,20+/m1/s1
SMILES	COC1=CC2=C(C=C1OC)[C@@H](C1=CC=C3OCOC3=C1)[C@H]1C(=O)OCC1C2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	368.13	Volume:	363.276 ? Van der Waals volume.
Dense:	1.013	LogP:	2.499 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.607 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.398 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	26.0
TPSA:	63.22 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.777	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.452	Fsp³:	0.381
MCE-18:	88.759 ? 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:	0.28	Fluc inhibitor:	0.672 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.309 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.068 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.144	Promiscuous compounds:	0.225

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.824	MDCK Permeability:	-4.709
Pgp-inhibitor:	0.6	Pgp-substrate:	0.008
PAMPA:	0.008 ? 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%):	0.004	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.06

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.782	MRP1:	0.967
Plasma Protein Binding (PPB):	98.033%	Volume Distribution (VD):	0.194
Fu:	1.863% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.845	BCRP inhibitor:	0.01
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	1.0	CYP1A2-substrate:	0.188
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.108
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.015	CYP2C8-inhibitor:	0.997
HLM stability:	0.888 ? 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):

4.208

Half-life (T1/2):

2.246

ADMET: Toxicity

hERG Blockers:	0.283	hERG Blockers (10um):	0.721
Human Hepatotoxicity (H-HT):	0.983	Drug-induced Liver Injury (DILI):	0.886
AMES Toxicity:	0.536	Rat Oral Acute Toxicity:	0.321
Maximum Recommended Daily Dose:	0.894	Skin Sensitization:	0.73
Carcinogencity:	0.721	Eye Corrosion:	0.005
Eye Irritation:	0.837	Respiratory Toxicity:	0.28
Drug-induced Neurotoxicity:	0.447	Ototoxicity:	0.927
Hematotoxicity:	0.67	Drug-induced Nephrotoxicity:	0.937
Genotoxicity:	0.795	RPMI-8226 Immunitoxicity:	0.053
A549 Cytotoxicity:	0.045	Hek293 Cytotoxicity:	0.492
BCF:	1.677 ? 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:	4.286 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.664 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.545 ? 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
NPO53594	Apis species	Genus	Apidae	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

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 NPC537076 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	27399
0.1-0.2	20686
0.2-0.3	1449
0.3-0.4	225
0.4-0.5	63
0.5-0.6	19
0.6-0.7	3
0.7-0.8	0
0.8-0.85	7
0.85-0.9	0
0.9-0.95	3
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9423	High Similarity	NPC218092
0.9423	High Similarity	NPC246474
0.9423	High Similarity	NPC162851
0.8214	Intermediate Similarity	NPC80230
0.8214	Intermediate Similarity	NPC104024
0.8214	Intermediate Similarity	NPC101755
0.8214	Intermediate Similarity	NPC304687
0.8214	Intermediate Similarity	NPC65574
0.807	Intermediate Similarity	NPC262455
0.807	Intermediate Similarity	NPC177476
0.7377	Intermediate Similarity	NPC30009
0.7377	Intermediate Similarity	NPC103197
0.625	Remote Similarity	NPC149505
0.625	Remote Similarity	NPC480477
0.6	Remote Similarity	NPC17348
0.5974	Remote Similarity	NPC115624
0.5797	Remote Similarity	NPC288149
0.5797	Remote Similarity	NPC115281
0.5797	Remote Similarity	NPC470637
0.5763	Remote Similarity	NPC177167
0.5645	Remote Similarity	NPC205915
0.5493	Remote Similarity	NPC163527
0.5373	Remote Similarity	NPC196420
0.5303	Remote Similarity	NPC239890
0.5303	Remote Similarity	NPC209411
0.5246	Remote Similarity	NPC110958
0.5246	Remote Similarity	NPC19890
0.5231	Remote Similarity	NPC176586
0.5231	Remote Similarity	NPC210354
0.5224	Remote Similarity	NPC605069
0.5152	Remote Similarity	NPC191158
0.5152	Remote Similarity	NPC177644
0.5072	Remote Similarity	NPC237946
0.5072	Remote Similarity	NPC32373

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC537076 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4942
0.1-0.2	4048
0.2-0.3	143
0.3-0.4	11
0.4-0.5	3
0.5-0.6	3
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
0.5072	Remote Similarity	NPD4965	Approved
0.5072	Remote Similarity	NPD4966	Phase 4
0.5072	Remote Similarity	NPD4967	Phase 2

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