NPASS Compound

Natural Product: NPC477886

Natural Product ID	NPC477886
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	tiegusanin N
IUPAC Name	5-[4-(3,4-dimethoxyphenyl)-2,3-dimethylbutyl]-1,2,3-trimethoxybenzene
Synonyms	Tiegusanin N
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	44179428
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 60 61 0 0 0 0 0 0 0 0999 V2000 -0.3867 1.0177 0.4577 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8820 1.3774 -0.9068 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4360 0.1640 -1.6192 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5763 -0.4682 -0.9209 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3676 -1.5348 -0.0783 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4260 -2.1415 0.6060 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.7036 -1.6594 0.4304 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9076 -0.5829 -0.4220 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8764 0.0186 -1.0969 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.7420 -2.2716 1.1157 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.0606 -1.7878 0.9460 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2361 -3.2175 1.4603 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9950 -3.8075 1.7313 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0912 2.1377 -1.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5970 2.4318 -3.1168 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3579 1.4907 -2.1014 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2832 1.0781 -1.0654 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2423 1.9023 -0.4945 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1325 1.4983 0.4682 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0749 0.1776 0.9045 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1515 -0.6736 0.3763 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2639 -0.2177 -0.6033 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1341 -1.9802 0.8442 O 0 0 0 0 0 0 0 0 0 0 0 0 2.2741 -2.9916 0.4341 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9961 -0.1853 1.8803 O 0 0 0 0 0 0 0 0 0 0 0 0 4.6784 -0.0512 3.2715 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0762 2.3698 1.0074 O 0 0 0 0 0 0 0 0 0 0 0 0 5.0840 3.6979 0.5220 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1684 1.3605 1.2081 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5118 1.6156 0.7569 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2686 -0.0485 0.6591 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8169 2.0218 -0.7411 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6683 -0.6282 -1.7488 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7853 0.4029 -2.6428 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4089 -1.9932 0.1163 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9060 -0.2129 -0.5539 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0747 0.8515 -1.7494 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.4730 -2.1194 -0.0159 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6431 -2.1704 1.8248 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1029 -0.6652 1.0400 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7891 -4.5680 0.9420 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0984 -4.3099 2.7371 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1646 -3.0904 1.8184 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1837 3.1504 -1.2969 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5904 2.8557 -2.9708 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0367 3.2267 -3.5826 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5364 1.5580 -3.7683 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9317 2.1527 -2.8126 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1340 0.5854 -2.7272 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2893 2.9195 -0.8279 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5666 -0.9563 -0.9686 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2681 -2.6528 0.1097 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7266 -3.4990 -0.4649 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0860 -3.7598 1.2123 H 0 0 0 0 0 0 0 0 0 0 0 0 4.0399 0.8214 3.4616 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6275 0.0959 3.8151 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1213 -0.9440 3.6309 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2001 4.2540 0.9073 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1542 3.7062 -0.5828 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9702 4.2486 0.9432 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 2 0 5 6 1 0 6 7 2 0 7 8 1 0 8 9 2 0 7 10 1 0 10 11 1 0 6 12 1 0 12 13 1 0 2 14 1 0 14 15 1 0 14 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 21 23 1 0 23 24 1 0 20 25 1 0 25 26 1 0 19 27 1 0 27 28 1 0 9 4 1 0 22 17 1 0 1 29 1 0 1 30 1 0 1 31 1 0 2 32 1 0 3 33 1 0 3 34 1 0 5 35 1 0 8 36 1 0 9 37 1 0 11 38 1 0 11 39 1 0 11 40 1 0 13 41 1 0 13 42 1 0 13 43 1 0 14 44 1 0 15 45 1 0 15 46 1 0 15 47 1 0 16 48 1 0 16 49 1 0 18 50 1 0 22 51 1 0 24 52 1 0 24 53 1 0 24 54 1 0 26 55 1 0 26 56 1 0 26 57 1 0 28 58 1 0 28 59 1 0 28 60 1 0 M END

Standard InCHIKey	SDTABXKGPYKKJI-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C23H32O5/c1-15(10-17-8-9-19(24-3)20(12-17)25-4)16(2)11-18-13-21(26-5)23(28-7)22(14-18)27-6/h8-9,12-16H,10-11H2,1-7H3
SMILES	CC(CC1=CC(=C(C=C1)OC)OC)C(C)CC2=CC(=C(C(=C2)OC)OC)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	388.22	Volume:	417.384 ? Van der Waals volume.
Dense:	0.93	LogP:	4.58 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.821 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.727 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	12.0
TPSA:	46.15 ? Topological Polar Surface Area.	H-Bond Acceptor:	5.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	5.0

MedChem Properties

QED Drug-Likeness Score:	0.586	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.823	Fsp³:	0.478
MCE-18:	30.0 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.354	Fluc inhibitor:	0.066 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.013 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.293 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.48	Promiscuous compounds:	0.11

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.637	MDCK Permeability:	-4.579
Pgp-inhibitor:	0.899	Pgp-substrate:	0.068
PAMPA:	0.0 ? 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):	0.001
20% Bioavailability (F20%):	0.039	30% Bioavailability (F30%):	0.028
50% Bioavailability (F50%):	0.676

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.771	MRP1:	0.996
Plasma Protein Binding (PPB):	93.143%	Volume Distribution (VD):	0.02
Fu:	5.318% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.946
OATP1B3 inhibitor:	0.813	BCRP inhibitor:	0.404
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.285	CYP1A2-substrate:	0.102
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.407	CYP2C9-substrate:	0.784
CYP2D6-inhibitor:	0.007	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.926	CYP2C8-inhibitor:	1.0
HLM stability:	0.989 ? 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):

6.846

Half-life (T1/2):

1.037

ADMET: Toxicity

hERG Blockers:	0.59	hERG Blockers (10um):	0.852
Human Hepatotoxicity (H-HT):	0.724	Drug-induced Liver Injury (DILI):	0.16
AMES Toxicity:	0.1	Rat Oral Acute Toxicity:	0.108
Maximum Recommended Daily Dose:	0.233	Skin Sensitization:	0.31
Carcinogencity:	0.179	Eye Corrosion:	0.021
Eye Irritation:	0.38	Respiratory Toxicity:	0.448
Drug-induced Neurotoxicity:	0.674	Ototoxicity:	0.803
Hematotoxicity:	0.378	Drug-induced Nephrotoxicity:	0.314
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.178
A549 Cytotoxicity:	0.29	Hek293 Cytotoxicity:	0.511
BCF:	2.738 ? 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:	4.584 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.573 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.366 ? 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
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1002/cjoc.20010190319]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	DOI[10.1016/j.tet.2008.10.079]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[11395273]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	stem	n.a.	PMID[18536373]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	aerial parts	Erlang Mountain area of Sichuan Province, China	2007-SEP	PMID[19413342]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20681569]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7850	Schisandra propinqua	Species	Schisandraceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO7850	Schisandra propinqua	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
EC50	1
Ratio CC50/EC50	1
CC50	1

Activity Type	# Activity
Cell line	1
Organism	1
Others	1

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
NPT1452	Cell line	C8166	Homo sapiens	CC50	=	24500	nM	PMID[19413342]
NPT24	Organism	Human immunodeficiency virus 1	Human immunodeficiency virus 1	EC50	=	9400	nM	PMID[19413342]
NPT2	Others	Unspecified	n.a.	Ratio CC50/EC50	=	2.6	n.a.	PMID[19413342]

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 NPC477886 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	24398
0.1-0.2	21680
0.2-0.3	3254
0.3-0.4	387
0.4-0.5	115
0.5-0.6	11
0.6-0.7	6
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.871	High Similarity	NPC165106
0.7105	Intermediate Similarity	NPC344161
0.6571	Remote Similarity	NPC254625
0.6429	Remote Similarity	NPC227217
0.6429	Remote Similarity	NPC117780
0.6053	Remote Similarity	NPC80241
0.6053	Remote Similarity	NPC301641
0.6053	Remote Similarity	NPC485483
0.5897	Remote Similarity	NPC81067
0.5897	Remote Similarity	NPC602945
0.587	Remote Similarity	NPC211386
0.5556	Remote Similarity	NPC196937
0.5556	Remote Similarity	NPC292792
0.5417	Remote Similarity	NPC143895
0.5319	Remote Similarity	NPC192255
0.5263	Remote Similarity	NPC120075
0.5102	Remote Similarity	NPC274356
0.5102	Remote Similarity	NPC101748
0.5098	Remote Similarity	NPC474017

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC477886 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3857
0.1-0.2	4870
0.2-0.3	377
0.3-0.4	43
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.871	High 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