NPASS Compound

Natural Product: NPC344161

Natural Product ID	NPC344161
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-[(2S,3R)-4-(3,4-Dimethoxyphenyl)-2,3-Dimethylbutyl]-1,3-Benzodioxole
IUPAC Name	5-[(2S,3R)-4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-1,3-benzodioxole
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL3290508
PubChem CID	14057534
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0001392] Lignans, neolignans and related compounds [CHEMONTID:0001969] Dibenzylbutane lignans

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 51 53 0 0 0 0 0 0 0 0999 V2000 -5.3263 -1.5935 -1.3243 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2439 -0.6345 -0.2829 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0952 0.1073 -0.1450 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9892 -0.0381 -0.9913 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8732 0.7442 -0.7871 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7979 1.6799 0.2320 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8888 1.8208 1.0638 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0192 1.0379 0.8679 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1092 1.1893 1.7112 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1175 2.1205 2.7764 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7014 0.5882 -1.6816 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2953 -0.4324 -1.1684 C 0 0 2 0 0 0 0 0 0 0 0 0 1.4276 -0.5009 -2.1509 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5057 -1.4763 -1.7490 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1309 -1.1189 -0.4239 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6157 -1.6036 0.7469 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1905 -1.2759 1.9478 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3096 -0.4427 1.9860 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8276 0.0441 0.8122 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2355 -0.2978 -0.3730 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9393 0.8512 1.0933 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9698 1.0604 2.4992 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0896 0.0531 3.0152 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9675 0.8724 -2.4640 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4284 -1.7618 -1.0538 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4253 -2.2595 -1.2414 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2639 -2.1656 -1.2952 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2001 -1.0308 -2.2776 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0909 -0.7723 -1.7679 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8975 2.2530 0.3304 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8273 2.5547 1.8618 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5263 1.7103 3.6441 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6820 3.0922 2.5179 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1702 2.2089 3.1185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0779 0.2088 -2.6522 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2233 1.5743 -1.8943 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7071 -0.1974 -0.1780 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0413 -0.8872 -3.1454 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3375 -1.4714 -2.4815 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1513 -2.5023 -1.6611 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7629 -2.2453 0.7606 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8333 -1.6245 2.9090 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6570 0.0927 -1.3160 H 0 0 0 0 0 0 0 0 0 0 0 0 7.0135 0.8987 2.8381 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6211 2.0713 2.7454 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3150 1.4093 -3.1874 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9975 1.4718 -1.5334 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0070 0.8198 -2.8588 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2240 -2.6315 -1.0111 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9892 -1.8662 -2.0301 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2091 -1.7048 -0.2712 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 5 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 1 0 13 24 1 0 12 25 1 0 8 3 1 0 20 15 1 0 23 18 1 0 1 26 1 0 1 27 1 0 1 28 1 0 4 29 1 0 6 30 1 0 7 31 1 0 10 32 1 0 10 33 1 0 10 34 1 0 11 35 1 0 11 36 1 0 12 37 1 1 13 38 1 6 14 39 1 0 14 40 1 0 16 41 1 0 17 42 1 0 20 43 1 0 22 44 1 0 22 45 1 0 24 46 1 0 24 47 1 0 24 48 1 0 25 49 1 0 25 50 1 0 25 51 1 0 M END

Standard InCHIKey	ZANBLNRUVUOABN-CABCVRRESA-N
Standard InCHI	InChI=1S/C21H26O4/c1-14(9-16-5-7-18(22-3)20(11-16)23-4)15(2)10-17-6-8-19-21(12-17)25-13-24-19/h5-8,11-12,14-15H,9-10,13H2,1-4H3/t14-,15+/m1/s1
SMILES	COc1cc(ccc1OC)C[C@H]([C@H](Cc1ccc2c(c1)OCO2)C)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	342.18	Volume:	365.445 ? Van der Waals volume.
Dense:	0.936	LogP:	3.254 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.156 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.209 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	16.0
TPSA:	36.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.743	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.831	Fsp³:	0.429
MCE-18:	52.133 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.541	Fluc inhibitor:	0.59 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.024 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.083 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.473	Promiscuous compounds:	0.124

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.826	MDCK Permeability:	-4.701
Pgp-inhibitor:	0.572	Pgp-substrate:	0.016
PAMPA:	0.018 ? 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%):	0.077	30% Bioavailability (F30%):	0.118
50% Bioavailability (F50%):	0.974

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.244
Plasma Protein Binding (PPB):	96.775%	Volume Distribution (VD):	0.055
Fu:	3.451% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.56
OATP1B3 inhibitor:	0.722	BCRP inhibitor:	0.282
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.986	CYP1A2-substrate:	0.967
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.997	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.985	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.992	CYP2C8-inhibitor:	1.0
HLM stability:	0.999 ? 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):

5.733

Half-life (T1/2):

0.726

ADMET: Toxicity

hERG Blockers:	0.486	hERG Blockers (10um):	0.827
Human Hepatotoxicity (H-HT):	0.621	Drug-induced Liver Injury (DILI):	0.589
AMES Toxicity:	0.325	Rat Oral Acute Toxicity:	0.135
Maximum Recommended Daily Dose:	0.075	Skin Sensitization:	0.777
Carcinogencity:	0.458	Eye Corrosion:	0.921
Eye Irritation:	0.996	Respiratory Toxicity:	0.063
Drug-induced Neurotoxicity:	0.417	Ototoxicity:	0.565
Hematotoxicity:	0.537	Drug-induced Nephrotoxicity:	0.664
Genotoxicity:	0.012	RPMI-8226 Immunitoxicity:	0.173
A549 Cytotoxicity:	0.23	Hek293 Cytotoxicity:	0.331
BCF:	2.655 ? 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:	4.542 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.898 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.43 ? 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
NPO19979	Schisandra glaucescens	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[23373215]
NPO19979	Schisandra glaucescens	Species	Schisandraceae	Eukaryota	fruit	n.a.	n.a.	PMID[24927000]
NPO19979	Schisandra glaucescens	Species	Schisandraceae	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
Activity	4

Activity Type	# Activity
Individual protein	4

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT78	Individual protein	Beta amyloid A4 protein	Homo sapiens	Activity	=	58.1	%	PMID[26584085]
NPT78	Individual protein	Beta amyloid A4 protein	Homo sapiens	Activity	=	62.2	%	DrugMatrix in vivo data: Biochemistry
NPT78	Individual protein	Beta amyloid A4 protein	Homo sapiens	Activity	=	61.1	%	PMID[1965654]
NPT78	Individual protein	Beta amyloid A4 protein	Homo sapiens	Activity	=	61.9	%	PubChem BioAssay data set

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 NPC344161 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	24992
0.1-0.2	21465
0.2-0.3	2706
0.3-0.4	496
0.4-0.5	139
0.5-0.6	36
0.6-0.7	16
0.7-0.8	1
0.8-0.85	0
0.85-0.9	3
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8824	High Similarity	NPC80241
0.8824	High Similarity	NPC301641
0.8824	High Similarity	NPC485483
0.7941	Intermediate Similarity	NPC165106
0.7111	Intermediate Similarity	NPC274356
0.7111	Intermediate Similarity	NPC101748
0.7105	Intermediate Similarity	NPC477886
0.6977	Remote Similarity	NPC249788
0.6667	Remote Similarity	NPC485480
0.6591	Remote Similarity	NPC485482
0.65	Remote Similarity	NPC604144
0.6341	Remote Similarity	NPC40352
0.6341	Remote Similarity	NPC213711
0.6304	Remote Similarity	NPC104077
0.6304	Remote Similarity	NPC219671
0.6304	Remote Similarity	NPC147616
0.6222	Remote Similarity	NPC196937
0.6136	Remote Similarity	NPC476748
0.6122	Remote Similarity	NPC205915
0.6047	Remote Similarity	NPC600801
0.6042	Remote Similarity	NPC143895
0.6	Remote Similarity	NPC227217
0.6	Remote Similarity	NPC117780
0.5962	Remote Similarity	NPC487677
0.5962	Remote Similarity	NPC487675
0.5962	Remote Similarity	NPC46880
0.5957	Remote Similarity	NPC192255
0.5957	Remote Similarity	NPC474288
0.5918	Remote Similarity	NPC165128
0.5897	Remote Similarity	NPC31279
0.58	Remote Similarity	NPC28398
0.5741	Remote Similarity	NPC106739
0.5636	Remote Similarity	NPC471505
0.5536	Remote Similarity	NPC487679
0.5536	Remote Similarity	NPC487678
0.5532	Remote Similarity	NPC606623
0.5476	Remote Similarity	NPC81067
0.5476	Remote Similarity	NPC602945
0.5435	Remote Similarity	NPC57119
0.5435	Remote Similarity	NPC158471
0.5435	Remote Similarity	NPC226862
0.54	Remote Similarity	NPC158737
0.5306	Remote Similarity	NPC110958
0.5306	Remote Similarity	NPC19890
0.5294	Remote Similarity	NPC17348
0.5283	Remote Similarity	NPC176586
0.5283	Remote Similarity	NPC210354
0.5273	Remote Similarity	NPC487681
0.5217	Remote Similarity	NPC197166
0.52	Remote Similarity	NPC171550
0.52	Remote Similarity	NPC134764
0.5185	Remote Similarity	NPC185908
0.5185	Remote Similarity	NPC191158
0.5185	Remote Similarity	NPC177644
0.5185	Remote Similarity	NPC482891
0.5179	Remote Similarity	NPC161249
0.5128	Remote Similarity	NPC292792
0.5094	Remote Similarity	NPC284464
0.5091	Remote Similarity	NPC258644

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC344161 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4117
0.1-0.2	4674
0.2-0.3	322
0.3-0.4	32
0.4-0.5	3
0.5-0.6	1
0.6-0.7	0
0.7-0.8	1
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
0.7941	Intermediate Similarity	NPD5283	Phase 2
0.5952	Remote Similarity	NPD554	Phase 3

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