NPASS Compound

Natural Product: NPC516782

Natural Product ID	NPC516782
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(3~{S},4~{R})-4-[bis(7-methoxy-1,3-benzodioxol-5-yl)methyl]-3-methyl-tetrahydrofuran-2-one
IUPAC Name	(3~{S},4~{R})-4-[bis(7-methoxy-1,3-benzodioxol-5-yl)methyl]-3-methyl-tetrahydrofuran-2-one
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 56 0 0 0 0 0 0 0 0999 V2000 -4.4380 -1.1145 -1.8182 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1151 -1.8486 -0.6758 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0047 -1.5609 0.0865 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1605 -0.5270 -0.2517 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0382 -0.2085 0.4877 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1923 0.9146 0.0519 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8437 0.4178 -0.8783 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0900 -0.0131 -0.4706 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0378 -0.4728 -1.3609 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2753 -0.8945 -0.9009 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5919 -0.8639 0.4753 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7408 -0.5086 -2.7167 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4957 -0.9176 -3.8151 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6313 -0.9855 -4.9312 C 0 0 0 0 0 0 0 0 0 0 0 0 1.5114 -0.2388 -4.5294 O 0 0 0 0 0 0 0 0 0 0 0 0 1.4932 -0.0804 -3.1534 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5515 0.3814 -2.2233 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4918 1.6340 1.1761 C 0 0 1 0 0 0 0 0 0 0 0 0 1.3202 2.7523 0.6072 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4028 3.6894 1.6683 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5203 3.3780 2.6810 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5474 3.8270 3.8358 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4476 2.3969 2.0658 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4408 3.2325 1.2974 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7947 -0.9857 1.6009 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6471 -2.0396 1.9535 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7588 -2.3326 1.1959 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4118 -3.4286 1.7908 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5002 -4.0519 2.6994 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6432 -2.9599 2.9934 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2340 -1.6870 -2.3718 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5649 -0.9282 -2.4752 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8978 -0.1239 -1.6040 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3893 0.0518 -1.1271 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7794 1.6944 -0.5024 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3798 -0.0081 0.5809 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8107 0.1807 0.8211 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8523 -1.3591 1.1129 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5572 -1.4153 0.6305 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1255 -0.4155 -5.7548 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4061 -2.0253 -5.2063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3922 0.6947 -2.6493 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0769 0.9522 1.8196 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3140 2.4251 0.2559 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7498 3.2256 -0.2063 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9185 1.8068 2.8466 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1493 2.6264 0.6980 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9233 4.0065 0.6987 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0592 3.7665 2.0521 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0605 -0.7715 2.1962 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9792 -4.8349 2.0895 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9980 -4.4529 3.5877 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 2 0 8 9 1 0 9 10 1 0 10 11 1 0 9 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 6 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 5 25 2 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 1 0 29 30 1 0 27 3 1 0 17 7 1 0 23 18 1 0 30 26 1 0 16 12 1 0 1 31 1 0 1 32 1 0 1 33 1 0 4 34 1 0 6 35 1 0 8 36 1 0 11 37 1 0 11 38 1 0 11 39 1 0 14 40 1 0 14 41 1 0 17 42 1 0 18 43 1 1 19 44 1 0 19 45 1 0 23 46 1 1 24 47 1 0 24 48 1 0 24 49 1 0 25 50 1 0 29 51 1 0 29 52 1 0 M END

Standard InCHIKey	UYKJDDXZIMXQNB-FZMZJTMJSA-N
Standard InCHI	InChI=1S/C22H22O8/c1-11-14(8-26-22(11)23)19(12-4-15(24-2)20-17(6-12)27-9-29-20)13-5-16(25-3)21-18(7-13)28-10-30-21/h4-7,11,14,19H,8-10H2,1-3H3/t11-,14-/m0/s1
SMILES	COC1=CC(C(C2=CC(OC)=C3OCOC3=C2)[C@H]2COC(=O)[C@H]2C)=CC2=C1OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	414.13	Volume:	398.152 ? Van der Waals volume.
Dense:	1.04	LogP:	2.345 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.581 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.26 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	26.0
TPSA:	81.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	5.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.691	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.724	Fsp³:	0.409
MCE-18:	89.71 ? 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:	0	PAINS Alert:	0
Colloidal aggregators:	0.28	Fluc inhibitor:	0.055 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.074 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.313 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.254	Promiscuous compounds:	0.111

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.001	MDCK Permeability:	-4.735
Pgp-inhibitor:	0.15	Pgp-substrate:	0.001
PAMPA:	0.074 ? 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%):	0.002	30% Bioavailability (F30%):	0.0
50% Bioavailability (F50%):	0.055

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.612	MRP1:	0.988
Plasma Protein Binding (PPB):	96.514%	Volume Distribution (VD):	0.101
Fu:	3.337% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.967	BCRP inhibitor:	0.008
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.998	CYP1A2-substrate:	0.977
CYP2C19-inhibitor:	1.0	CYP2C19-substrate:	1.0
CYP2C9-inhibitor:	0.048	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	1.0	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.999
HLM stability:	0.997 ? 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):

3.095

Half-life (T1/2):

1.157

ADMET: Toxicity

hERG Blockers:	0.19	hERG Blockers (10um):	0.506
Human Hepatotoxicity (H-HT):	0.906	Drug-induced Liver Injury (DILI):	0.977
AMES Toxicity:	0.505	Rat Oral Acute Toxicity:	0.265
Maximum Recommended Daily Dose:	0.856	Skin Sensitization:	0.775
Carcinogencity:	0.821	Eye Corrosion:	0.0
Eye Irritation:	0.611	Respiratory Toxicity:	0.067
Drug-induced Neurotoxicity:	0.738	Ototoxicity:	0.772
Hematotoxicity:	0.827	Drug-induced Nephrotoxicity:	0.957
Genotoxicity:	0.995	RPMI-8226 Immunitoxicity:	0.233
A549 Cytotoxicity:	0.081	Hek293 Cytotoxicity:	0.391
BCF:	1.492 ? 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:	3.954 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.133 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.921 ? 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
NPO56930	Peperomia dindigulensis	Genus	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO51908	Peperomia dindygulensis Miq.	Genus	Piperaceae	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 NPC516782 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	20499
0.1-0.2	26771
0.2-0.3	2176
0.3-0.4	297
0.4-0.5	78
0.5-0.6	23
0.6-0.7	7
0.7-0.8	0
0.8-0.85	3
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	NPC218841
0.9756	High Similarity	NPC151423
0.8333	Intermediate Similarity	NPC477695
0.8049	Intermediate Similarity	NPC44245
0.8	Intermediate Similarity	NPC474965
0.7347	Intermediate Similarity	NPC164082
0.72	Intermediate Similarity	NPC477698
0.6735	Remote Similarity	NPC477696
0.6667	Remote Similarity	NPC56091
0.6607	Remote Similarity	NPC477699
0.6531	Remote Similarity	NPC193779
0.6471	Remote Similarity	NPC470811
0.6471	Remote Similarity	NPC477697
0.64	Remote Similarity	NPC475000
0.569	Remote Similarity	NPC262455
0.569	Remote Similarity	NPC177476
0.5614	Remote Similarity	NPC477700
0.5593	Remote Similarity	NPC480477
0.549	Remote Similarity	NPC11453
0.5472	Remote Similarity	NPC92693
0.537	Remote Similarity	NPC40237
0.5345	Remote Similarity	NPC239890
0.5345	Remote Similarity	NPC209411
0.5333	Remote Similarity	NPC149505
0.5254	Remote Similarity	NPC80230
0.5254	Remote Similarity	NPC104024
0.5254	Remote Similarity	NPC101755
0.5254	Remote Similarity	NPC304687
0.5254	Remote Similarity	NPC65574
0.5238	Remote Similarity	NPC273578
0.5161	Remote Similarity	NPC210642
0.5161	Remote Similarity	NPC13985
0.5161	Remote Similarity	NPC207584
0.5161	Remote Similarity	NPC19947
0.5091	Remote Similarity	NPC23336
0.5082	Remote Similarity	NPC237946
0.5082	Remote Similarity	NPC32373

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC516782 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4285
0.1-0.2	4691
0.2-0.3	162
0.3-0.4	9
0.4-0.5	0
0.5-0.6	3
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
0.5082	Remote Similarity	NPD4965	Approved
0.5082	Remote Similarity	NPD4966	Phase 4
0.5082	Remote Similarity	NPD4967	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