NPASS Compound

Natural Product: NPC170694

Natural Product ID	NPC170694
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Nitidanin
IUPAC Name	4-[(2S,3S)-3-(hydroxymethyl)-7-[(E)-3-hydroxyprop-1-enyl]-5-methoxy-2,3-dihydro-1,4-benzodioxin-2-yl]-2,6-dimethoxyphenol
Synonyms	Nitidanin
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL479693
PubChem CID	11188887
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0002699] Benzodioxanes [CHEMONTID:0002704] Phenylbenzodioxanes [CHEMONTID:0002707] Phenylbenzo-1,4-dioxanes

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 53 55 0 0 0 0 0 0 0 0999 V2000 -3.0459 -3.7526 2.3685 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0045 -3.2300 1.4889 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7270 -2.1244 0.7259 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5271 -1.4432 0.7457 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2989 -0.3345 -0.0432 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3089 0.1004 -0.8762 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5184 -0.5650 -0.9134 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7372 -1.6720 -0.1213 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9482 -2.3190 -0.1740 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5256 -0.0914 -1.7764 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3155 1.0401 -2.5924 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0299 0.4022 -0.0352 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.8664 1.2776 1.1876 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.1026 2.0966 1.4673 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8554 2.8751 2.5951 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2650 2.0934 0.9466 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4153 1.4677 0.4805 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6524 2.0819 0.5094 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7673 1.4233 0.0361 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7117 0.1370 -0.4839 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9408 -0.5109 -0.9735 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9962 -1.7092 -1.4772 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3042 -2.2524 -1.9379 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2705 -2.5664 -3.2917 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4798 -0.4730 -0.5121 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3469 0.1904 -0.0335 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1014 -0.4481 -0.0709 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7139 3.3630 1.0262 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9556 4.0120 1.0686 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2529 -4.8052 2.6635 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9949 -3.1681 3.3200 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0449 -3.7566 1.8821 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7432 -1.7963 1.4049 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1767 0.9802 -1.5257 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3887 -2.8182 0.5618 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9484 1.8869 -1.9705 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2704 1.3014 -3.0905 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5716 0.8437 -3.3972 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9515 1.0619 -0.9224 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7097 0.6006 2.0535 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3702 2.7713 0.6460 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9268 1.4039 1.7334 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0537 3.8313 2.4602 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7450 1.9059 0.0578 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8864 0.0518 -0.9129 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0793 -2.2950 -1.5525 H 0 0 0 0 0 0 0 0 0 0 0 0 7.1068 -1.5181 -1.7303 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5729 -3.1550 -1.3162 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6252 -3.4859 -3.3863 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3718 -1.4571 -0.8980 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6722 3.5248 1.7745 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7909 5.0454 1.4138 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4434 3.9779 0.0625 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 7 10 1 0 10 11 1 0 5 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 13 16 1 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 21 22 2 0 22 23 1 0 23 24 1 0 20 25 1 0 25 26 2 0 26 27 1 0 18 28 1 0 28 29 1 0 8 3 1 0 27 12 1 0 26 17 1 0 1 30 1 0 1 31 1 0 1 32 1 0 4 33 1 0 6 34 1 0 9 35 1 0 11 36 1 0 11 37 1 0 11 38 1 0 12 39 1 6 13 40 1 1 14 41 1 0 14 42 1 0 15 43 1 0 19 44 1 0 21 45 1 0 22 46 1 0 23 47 1 0 23 48 1 0 24 49 1 0 25 50 1 0 29 51 1 0 29 52 1 0 29 53 1 0 M END

Standard InCHIKey	AZTAGXIJLPKJOR-BJUCQYRTSA-N
Standard InCHI	InChI=1S/C21H24O8/c1-25-14-9-13(10-15(26-2)19(14)24)20-18(11-23)29-21-16(27-3)7-12(5-4-6-22)8-17(21)28-20/h4-5,7-10,18,20,22-24H,6,11H2,1-3H3/b5-4+/t18-,20-/m0/s1
SMILES	COc1cc(cc(c1O)OC)[C@H]1[C@H](CO)Oc2c(cc(/C=C/CO)cc2O1)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	404.15	Volume:	397.969 ? Van der Waals volume.
Dense:	1.016	LogP:	2.044 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.36 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.863 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	18.0
TPSA:	106.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	3.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.645	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.493	Fsp³:	0.333
MCE-18:	59.714 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.437	Fluc inhibitor:	0.846 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.075 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.449 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.287	Promiscuous compounds:	0.742

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.467	MDCK Permeability:	-5.04
Pgp-inhibitor:	0.94	Pgp-substrate:	0.046
PAMPA:	0.014 ? 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):	0.003
20% Bioavailability (F20%):	0.071	30% Bioavailability (F30%):	0.386
50% Bioavailability (F50%):	0.849

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.074	MRP1:	0.634
Plasma Protein Binding (PPB):	88.659%	Volume Distribution (VD):	-0.165
Fu:	12.33% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.962
BSEP inhibitor:	0.998

ADMET: Metabolism

CYP1A2-inhibitor:	0.249	CYP1A2-substrate:	0.068
CYP2C19-inhibitor:	0.948	CYP2C19-substrate:	0.11
CYP2C9-inhibitor:	0.215	CYP2C9-substrate:	0.063
CYP2D6-inhibitor:	0.231	CYP2D6-substrate:	0.202
CYP3A4-inhibitor:	0.167	CYP3A4-substrate:	0.838
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.623
HLM stability:	0.144 ? 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):

8.347

Half-life (T1/2):

1.552

ADMET: Toxicity

hERG Blockers:	0.114	hERG Blockers (10um):	0.263
Human Hepatotoxicity (H-HT):	0.862	Drug-induced Liver Injury (DILI):	0.53
AMES Toxicity:	0.44	Rat Oral Acute Toxicity:	0.1
Maximum Recommended Daily Dose:	0.204	Skin Sensitization:	0.947
Carcinogencity:	0.461	Eye Corrosion:	0.003
Eye Irritation:	0.835	Respiratory Toxicity:	0.288
Drug-induced Neurotoxicity:	0.591	Ototoxicity:	0.53
Hematotoxicity:	0.316	Drug-induced Nephrotoxicity:	0.404
Genotoxicity:	0.27	RPMI-8226 Immunitoxicity:	0.158
A549 Cytotoxicity:	0.263	Hek293 Cytotoxicity:	0.189
BCF:	0.571 ? 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:	3.083 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.841 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.744 ? 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
NPO4645	Grewia bilamellata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[16562832]
NPO4645	Grewia bilamellata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7348	Streptomyces gannmycicus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7348	Streptomyces gannmycicus	Species	Streptomycetaceae	Bacteria	n.a.	n.a.	n.a.	Database[UNPD]
NPO4645	Grewia bilamellata	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[UNPD]
NPO4154	Cortinarius violaceus	Species	Cortinariaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO10592	Phascolosoma elongatum	Species	Phascolosomatidae	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
ED50	1
IC50	2

Activity Type	# Activity
Cell line	1
Organism	2

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
NPT91	Cell line	KB	Homo sapiens	ED50	>	99.0	uM	PMID[16562832]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	21200.0	nM	PMID[16562832]
NPT6	Organism	Plasmodium falciparum	Plasmodium falciparum	IC50	=	18400.0	nM	PMID[16562832]

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 NPC170694 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	26491
0.1-0.2	19949
0.2-0.3	3114
0.3-0.4	234
0.4-0.5	54
0.5-0.6	12
0.6-0.7	3
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8302	Intermediate Similarity	NPC193722
0.6667	Remote Similarity	NPC224876
0.6441	Remote Similarity	NPC83375
0.625	Remote Similarity	NPC184447
0.5763	Remote Similarity	NPC72529
0.5625	Remote Similarity	NPC229401
0.5556	Remote Similarity	NPC278469
0.5484	Remote Similarity	NPC30083
0.5397	Remote Similarity	NPC488544
0.5303	Remote Similarity	NPC481838
0.5238	Remote Similarity	NPC7903
0.5238	Remote Similarity	NPC160991
0.5205	Remote Similarity	NPC469559
0.5082	Remote Similarity	NPC309744
0.5079	Remote Similarity	NPC87725
0.5079	Remote Similarity	NPC263261

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC170694 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5753
0.1-0.2	3332
0.2-0.3	62
0.3-0.4	3
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