NPASS Compound

Natural Product: NPC577180

Natural Product ID	NPC577180
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	PTVAOGIYBMTHSN-UHFFFAOYSA-N
IUPAC Name	1-[2-(3,4-dimethoxyphenyl)vinyl]-3,5-dimethoxy-benzene
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000253] Stilbenes

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 42 43 0 0 0 0 0 0 0 0999 V2000 6.2735 -1.4922 -1.5579 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8877 -1.6047 -1.7054 O 0 0 0 0 0 0 0 0 0 0 0 0 3.9986 -0.8683 -0.9174 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6400 -0.9953 -1.0804 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7402 -0.2631 -0.2971 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3016 -0.4539 -0.5310 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5858 0.1962 0.1629 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0159 0.0072 -0.0689 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5407 -0.8450 -1.0086 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9279 -0.9670 -1.1664 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8054 -0.2513 -0.4006 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1574 -0.3892 -0.5751 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.7772 -1.2267 -1.5004 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3044 0.6065 0.5448 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2124 1.3244 1.3124 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6843 2.2063 2.2846 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9406 0.7269 0.7003 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2826 0.5756 0.6283 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6640 0.7145 0.8045 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1796 1.5740 1.7520 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5710 1.6906 1.9042 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5287 -0.0126 0.0263 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5991 -1.6515 -0.5087 H 0 0 0 0 0 0 0 0 0 0 0 0 6.6252 -0.4759 -1.8428 H 0 0 0 0 0 0 0 0 0 0 0 0 6.7547 -2.2630 -2.1899 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2394 -1.6691 -1.8231 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0141 -1.1508 -1.2974 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2913 0.9120 0.9495 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8923 -1.4355 -1.6418 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2640 -1.6647 -1.9341 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2263 -2.1675 -1.6939 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9528 -0.6546 -2.4474 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7577 -1.5424 -1.0584 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4713 2.7953 2.7920 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9678 2.8793 1.7277 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0828 1.5928 2.9886 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5599 1.4006 1.4426 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6387 1.1592 1.2538 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0619 0.7305 2.1589 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8073 2.3923 2.7333 H 0 0 0 0 0 0 0 0 0 0 0 0 6.0289 2.0348 0.9408 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6098 0.0732 0.1392 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 2 3 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 11 14 1 0 14 15 1 0 15 16 1 0 14 17 2 0 5 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 19 22 2 0 22 3 1 0 17 8 1 0 1 23 1 0 1 24 1 0 1 25 1 0 4 26 1 0 6 27 1 0 7 28 1 0 9 29 1 0 10 30 1 0 13 31 1 0 13 32 1 0 13 33 1 0 16 34 1 0 16 35 1 0 16 36 1 0 17 37 1 0 18 38 1 0 21 39 1 0 21 40 1 0 21 41 1 0 22 42 1 0 M END

Standard InCHIKey	PTVAOGIYBMTHSN-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H20O4/c1-19-15-9-14(10-16(12-15)20-2)6-5-13-7-8-17(21-3)18(11-13)22-4/h5-12H,1-4H3
SMILES	COC1=CC(C=CC2=CC=C(OC)C(OC)=C2)=CC(OC)=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	300.14	Volume:	319.477 ? Van der Waals volume.
Dense:	0.939	LogP:	3.916 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.958 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.342 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	13.0
TPSA:	36.92 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	2.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.758	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	1.868	Fsp³:	0.222
MCE-18:	12.0 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.886	Fluc inhibitor:	0.999 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.12 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.605 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.687	Promiscuous compounds:	0.21

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.761	MDCK Permeability:	-4.661
Pgp-inhibitor:	0.955	Pgp-substrate:	0.015
PAMPA:	0.002 ? 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):	0.097
20% Bioavailability (F20%):	0.087	30% Bioavailability (F30%):	0.031
50% Bioavailability (F50%):	0.611

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.011	MRP1:	0.486
Plasma Protein Binding (PPB):	81.49%	Volume Distribution (VD):	-0.063
Fu:	13.373% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.998
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.995
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.934	CYP1A2-substrate:	0.259
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.01
CYP2C9-inhibitor:	0.788	CYP2C9-substrate:	0.183
CYP2D6-inhibitor:	0.997	CYP2D6-substrate:	0.988
CYP3A4-inhibitor:	0.114	CYP3A4-substrate:	0.012
CYP2B6-substrate:	0.922	CYP2C8-inhibitor:	0.997
HLM stability:	0.597 ? 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):

9.167

Half-life (T1/2):

1.014

ADMET: Toxicity

hERG Blockers:	0.628	hERG Blockers (10um):	0.706
Human Hepatotoxicity (H-HT):	0.795	Drug-induced Liver Injury (DILI):	0.309
AMES Toxicity:	0.866	Rat Oral Acute Toxicity:	0.416
Maximum Recommended Daily Dose:	0.754	Skin Sensitization:	0.976
Carcinogencity:	0.666	Eye Corrosion:	0.002
Eye Irritation:	0.821	Respiratory Toxicity:	0.55
Drug-induced Neurotoxicity:	0.953	Ototoxicity:	0.771
Hematotoxicity:	0.216	Drug-induced Nephrotoxicity:	0.888
Genotoxicity:	0.017	RPMI-8226 Immunitoxicity:	0.264
A549 Cytotoxicity:	0.739	Hek293 Cytotoxicity:	0.568
BCF:	2.109 ? 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:	3.911 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.106 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.654 ? 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
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	rhizome	n.a.	n.a.	PMID[10714491]
NPO40842	Eugenia rigida	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[23547843]
NPO40842	Eugenia rigida	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[27618204]
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO40842	Eugenia rigida	Species	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO88	Rheum undulatum	Species	Polygonaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO88	Rheum undulatum	Species	Polygonaceae	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

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 NPC577180 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	31296
0.1-0.2	15743
0.2-0.3	2475
0.3-0.4	274
0.4-0.5	52
0.5-0.6	13
0.6-0.7	2
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	2

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC123948
1.0	High Similarity	NPC96122
0.7742	Intermediate Similarity	NPC82016
0.625	Remote Similarity	NPC166759
0.6176	Remote Similarity	NPC35543
0.5897	Remote Similarity	NPC473411
0.5897	Remote Similarity	NPC474565
0.5714	Remote Similarity	NPC310905
0.5686	Remote Similarity	NPC473412
0.5526	Remote Similarity	NPC228287
0.5526	Remote Similarity	NPC180508
0.55	Remote Similarity	NPC71579
0.549	Remote Similarity	NPC469698
0.5405	Remote Similarity	NPC179309
0.5263	Remote Similarity	NPC475961
0.525	Remote Similarity	NPC294941
0.5128	Remote Similarity	NPC227894
0.5128	Remote Similarity	NPC185738

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC577180 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5233
0.1-0.2	3672
0.2-0.3	221
0.3-0.4	16
0.4-0.5	4
0.5-0.6	2
0.6-0.7	1
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
0.6053	Remote Similarity	NPD2981	Phase 2
0.5897	Remote Similarity	NPD2983	Phase 3
0.5128	Remote Similarity	NPD5536	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