NPASS Compound

Natural Product: NPC492840

Natural Product ID	NPC492840
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	5-[(2~{S},3~{S})-4-(1,3-benzodioxol-5-yl)-2,3-dimethyl-butyl]-2,3-dimethoxy-phenol
IUPAC Name	5-[(2~{S},3~{S})-4-(1,3-benzodioxol-5-yl)-2,3-dimethyl-butyl]-2,3-dimethoxy-phenol
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 52 54 0 0 0 0 0 0 0 0999 V2000 -4.5484 2.0370 1.9973 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1826 0.8820 1.4891 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4167 0.0742 0.6230 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1183 0.3945 0.2899 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3870 -0.4062 -0.5567 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0069 -0.0249 -0.8831 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0164 -0.6012 0.0711 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.1949 -0.1676 1.4800 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3812 -0.2672 -0.4621 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6279 1.1989 -0.5866 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4132 -0.8418 0.4835 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8000 -0.5525 0.0233 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4480 -1.4372 -0.8159 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7354 -1.1928 -1.2575 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4244 -0.0650 -0.8834 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7057 0.4395 -1.1630 O 0 0 0 0 0 0 0 0 0 0 0 0 8.0038 1.4705 -0.2292 C 0 0 0 0 0 0 0 0 0 0 0 0 6.7007 1.8575 0.1667 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7928 0.8297 -0.0456 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4951 0.5791 0.3970 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9864 -1.5368 -1.0632 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2813 -1.8953 -0.7574 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8804 -3.0416 -1.2746 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9891 -1.0746 0.0929 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.3169 -1.3697 0.4552 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.4045 -0.8847 -0.3066 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6457 1.8083 2.5960 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2524 2.7142 1.1803 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2698 2.5205 2.7005 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7160 1.3032 0.7306 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9630 1.1040 -0.8673 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7782 -0.2977 -1.9330 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1054 -1.7063 0.0311 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1823 0.8224 1.7290 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3673 -0.8934 2.1364 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2576 -0.3105 1.7437 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5539 -0.7483 -1.4459 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6467 1.3141 -1.0573 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6830 1.7311 0.3698 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9369 1.6891 -1.3188 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2418 -0.4060 1.4984 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2213 -1.9255 0.5607 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9085 -2.3253 -1.1119 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2515 -1.8916 -1.9224 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5728 2.2893 -0.6776 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4935 1.0404 0.6819 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0156 1.2782 1.0453 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4224 -2.1932 -1.7424 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5331 -3.5204 -0.6620 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4826 -1.5050 -1.2308 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3001 -0.9317 0.3138 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1799 0.1470 -0.6320 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 1 0 7 9 1 0 9 10 1 0 9 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 5 21 2 0 21 22 1 0 22 23 1 0 22 24 2 0 24 25 1 0 25 26 1 0 24 3 1 0 20 12 1 0 19 15 1 0 1 27 1 0 1 28 1 0 1 29 1 0 4 30 1 0 6 31 1 0 6 32 1 0 7 33 1 1 8 34 1 0 8 35 1 0 8 36 1 0 9 37 1 6 10 38 1 0 10 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 13 43 1 0 14 44 1 0 17 45 1 0 17 46 1 0 20 47 1 0 21 48 1 0 23 49 1 0 26 50 1 0 26 51 1 0 26 52 1 0 M END

Standard InCHIKey	ZGHOATLFXGBJGZ-KBPBESRZSA-N
Standard InCHI	InChI=1S/C21H26O5/c1-13(7-15-5-6-18-19(10-15)26-12-25-18)14(2)8-16-9-17(22)21(24-4)20(11-16)23-3/h5-6,9-11,13-14,22H,7-8,12H2,1-4H3/t13-,14-/m0/s1
SMILES	COC1=CC(C[C@H](C)[C@@H](C)CC2=CC=C3OCOC3=C2)=CC(O)=C1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	358.18	Volume:	374.235 ? Van der Waals volume.
Dense:	0.957	LogP:	3.907 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.591 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.681 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	16.0
TPSA:	57.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	1.0	Rings:	3.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.804	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.098	Fsp³:	0.429
MCE-18:	55.2 ? 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:	1	PAINS Alert:	0
Colloidal aggregators:	0.506	Fluc inhibitor:	0.345 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.03 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.262 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.328	Promiscuous compounds:	0.287

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.018	MDCK Permeability:	-4.758
Pgp-inhibitor:	0.769	Pgp-substrate:	0.022
PAMPA:	0.003 ? 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%):	0.112	30% Bioavailability (F30%):	0.188
50% Bioavailability (F50%):	0.98

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.056	MRP1:	0.432
Plasma Protein Binding (PPB):	96.494%	Volume Distribution (VD):	-0.259
Fu:	3.622% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.606
OATP1B3 inhibitor:	0.512	BCRP inhibitor:	0.247
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.082	CYP1A2-substrate:	0.972
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.972	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.087	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	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):

4.437

Half-life (T1/2):

0.847

ADMET: Toxicity

hERG Blockers:	0.306	hERG Blockers (10um):	0.684
Human Hepatotoxicity (H-HT):	0.665	Drug-induced Liver Injury (DILI):	0.74
AMES Toxicity:	0.489	Rat Oral Acute Toxicity:	0.288
Maximum Recommended Daily Dose:	0.356	Skin Sensitization:	0.638
Carcinogencity:	0.652	Eye Corrosion:	0.285
Eye Irritation:	0.956	Respiratory Toxicity:	0.56
Drug-induced Neurotoxicity:	0.681	Ototoxicity:	0.412
Hematotoxicity:	0.462	Drug-induced Nephrotoxicity:	0.661
Genotoxicity:	0.26	RPMI-8226 Immunitoxicity:	0.163
A549 Cytotoxicity:	0.389	Hek293 Cytotoxicity:	0.469
BCF:	2.267 ? 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:	4.341 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.903 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.126 ? 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
NPO55807	Schisandra propinqua var.propinqua	Genus	Schisandraceae	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 NPC492840 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	21893
0.1-0.2	22782
0.2-0.3	4549
0.3-0.4	497
0.4-0.5	92
0.5-0.6	29
0.6-0.7	8
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
0.7209	Intermediate Similarity	NPC76451
0.72	Intermediate Similarity	NPC274356
0.72	Intermediate Similarity	NPC101748
0.7111	Intermediate Similarity	NPC344161
0.6977	Remote Similarity	NPC80241
0.6977	Remote Similarity	NPC301641
0.6977	Remote Similarity	NPC485483
0.6735	Remote Similarity	NPC249788
0.6471	Remote Similarity	NPC485480
0.614	Remote Similarity	NPC487677
0.614	Remote Similarity	NPC487675
0.614	Remote Similarity	NPC46880
0.5932	Remote Similarity	NPC106739
0.5893	Remote Similarity	NPC474017
0.5833	Remote Similarity	NPC471505
0.5769	Remote Similarity	NPC485482
0.5738	Remote Similarity	NPC487679
0.5738	Remote Similarity	NPC487678
0.5714	Remote Similarity	NPC28398
0.5614	Remote Similarity	NPC488984
0.5614	Remote Similarity	NPC488985
0.5577	Remote Similarity	NPC227217
0.5577	Remote Similarity	NPC117780
0.5556	Remote Similarity	NPC104077
0.5556	Remote Similarity	NPC165106
0.5556	Remote Similarity	NPC219671
0.5556	Remote Similarity	NPC147616
0.551	Remote Similarity	NPC40352
0.551	Remote Similarity	NPC213711
0.55	Remote Similarity	NPC487681
0.55	Remote Similarity	NPC474039
0.5472	Remote Similarity	NPC196937
0.541	Remote Similarity	NPC161249
0.5345	Remote Similarity	NPC284464
0.5273	Remote Similarity	NPC63574
0.5185	Remote Similarity	NPC606623
0.5106	Remote Similarity	NPC31279
0.5102	Remote Similarity	NPC477886
0.5094	Remote Similarity	NPC476748
0.5091	Remote Similarity	NPC232275
0.5088	Remote Similarity	NPC143895

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC492840 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3862
0.1-0.2	5005
0.2-0.3	266
0.3-0.4	13
0.4-0.5	3
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	Drug ID	Developmental Stage
0.5556	Remote Similarity	NPD5283	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