NPASS Compound

Natural Product: NPC528891

Natural Product ID	NPC528891
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	dimethyl (2~{S},3~{R})-2,3-bis(1,3-benzodioxol-5-ylmethyl)butanedioate
IUPAC Name	dimethyl (2~{S},3~{R})-2,3-bis(1,3-benzodioxol-5-ylmethyl)butanedioate
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 55 0 0 0 0 0 0 0 0999 V2000 -2.2335 3.9686 0.7431 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5194 2.9632 0.0913 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9420 1.8679 0.6490 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0844 1.7687 1.9295 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1867 0.8147 -0.0815 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0865 0.1708 -1.1302 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2529 -0.4440 -0.4490 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4250 0.2595 -0.2662 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4873 -0.3424 0.3776 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4286 -1.6368 0.8541 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3286 -2.4727 1.5254 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8951 -3.8074 1.3337 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4750 -3.6119 1.2460 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2691 -2.3574 0.6826 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1930 -1.7560 0.0337 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0587 1.3669 -0.6531 C 0 0 1 0 0 0 0 0 0 0 0 0 1.9507 0.3436 -1.3487 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4349 -0.7182 -0.4389 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8071 -1.9243 -0.2869 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2681 -2.9060 0.5838 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3903 -2.6509 1.3113 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1198 -3.3789 2.2547 O 0 0 0 0 0 0 0 0 0 0 0 0 5.4239 -2.8149 2.3440 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1594 -1.4576 2.0415 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0528 -1.4463 1.1861 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5895 -0.4868 0.3256 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9064 2.4871 -1.6064 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1867 2.8886 -2.0106 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0586 3.1100 -2.0618 O 0 0 0 0 0 0 0 0 0 0 0 0 2.0030 4.1903 -2.9756 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8482 4.5111 -0.0066 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4894 4.6697 1.1951 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9094 3.5922 1.5453 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0300 0.0045 0.6444 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4877 -0.5631 -1.6784 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4769 0.9787 -1.8095 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5109 1.2723 -0.6299 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3871 0.2214 0.5089 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3165 -4.1514 0.3705 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1513 -4.4593 2.1891 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3115 -2.3417 -0.0825 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6870 1.7651 0.1895 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4566 -0.1060 -2.2284 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8406 0.8869 -1.7284 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9268 -2.1768 -0.8462 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7496 -3.8384 0.6763 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1077 -3.2668 1.5862 H 0 0 0 0 0 0 0 0 0 0 0 0 5.8247 -2.8669 3.3604 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1026 0.4638 0.2194 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7540 5.1559 -2.4703 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2162 3.9452 -3.7190 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9635 4.3160 -3.4902 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 3 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 5 16 1 0 16 17 1 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 2 0 16 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 15 7 1 0 26 18 1 0 14 10 1 0 25 21 1 0 1 31 1 0 1 32 1 0 1 33 1 0 5 34 1 1 6 35 1 0 6 36 1 0 8 37 1 0 9 38 1 0 12 39 1 0 12 40 1 0 15 41 1 0 16 42 1 1 17 43 1 0 17 44 1 0 19 45 1 0 20 46 1 0 23 47 1 0 23 48 1 0 26 49 1 0 30 50 1 0 30 51 1 0 30 52 1 0 M END

Standard InCHIKey	YKLDSNGNWJIDLS-IYBDPMFKSA-N
Standard InCHI	InChI=1S/C22H22O8/c1-25-21(23)15(7-13-3-5-17-19(9-13)29-11-27-17)16(22(24)26-2)8-14-4-6-18-20(10-14)30-12-28-18/h3-6,9-10,15-16H,7-8,11-12H2,1-2H3/t15-,16+
SMILES	COC(=O)[C@@H](CC1=CC=C2OCOC2=C1)[C@@H](CC1=CC=C2OCOC2=C1)C(=O)OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	414.13	Volume:	404.072 ? Van der Waals volume.
Dense:	1.025	LogP:	2.85 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.925 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.095 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	9.0	Rigid Bonds:	22.0
TPSA:	89.52 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	4.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.639	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.233	Fsp³:	0.364
MCE-18:	68.933 ? 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:	0.14	Fluc inhibitor:	0.325 ? 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:	0.445 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.302	Promiscuous compounds:	0.118

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.953	MDCK Permeability:	-4.723
Pgp-inhibitor:	0.906	Pgp-substrate:	0.005
PAMPA:	0.041 ? 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%):	0.667	30% Bioavailability (F30%):	0.016
50% Bioavailability (F50%):	0.987

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.054	MRP1:	0.103
Plasma Protein Binding (PPB):	96.567%	Volume Distribution (VD):	-0.263
Fu:	4.374% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.997
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.007
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.005	CYP1A2-substrate:	1.0
CYP2C19-inhibitor:	0.018	CYP2C19-substrate:	0.968
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	0.959	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.999	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.031
HLM stability:	0.95 ? 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):

4.587

Half-life (T1/2):

0.622

ADMET: Toxicity

hERG Blockers:	0.407	hERG Blockers (10um):	0.625
Human Hepatotoxicity (H-HT):	0.933	Drug-induced Liver Injury (DILI):	0.955
AMES Toxicity:	0.472	Rat Oral Acute Toxicity:	0.182
Maximum Recommended Daily Dose:	0.911	Skin Sensitization:	0.423
Carcinogencity:	0.422	Eye Corrosion:	0.001
Eye Irritation:	0.833	Respiratory Toxicity:	0.137
Drug-induced Neurotoxicity:	0.88	Ototoxicity:	0.616
Hematotoxicity:	0.536	Drug-induced Nephrotoxicity:	0.912
Genotoxicity:	0.929	RPMI-8226 Immunitoxicity:	0.089
A549 Cytotoxicity:	0.034	Hek293 Cytotoxicity:	0.563
BCF:	1.431 ? 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:	3.87 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.992 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.969 ? 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
NPO16896	Justicia ciliata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10425143]
NPO16896	Justicia ciliata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[11087610]
NPO16935	Heliopsis buphthalmoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16896	Justicia ciliata	Species	Acanthaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16935	Heliopsis buphthalmoides	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16896	Justicia ciliata	Species	Acanthaceae	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 NPC528891 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	23639
0.1-0.2	23566
0.2-0.3	2110
0.3-0.4	402
0.4-0.5	88
0.5-0.6	33
0.6-0.7	15
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
0.8537	High Similarity	NPC474288
0.6889	Remote Similarity	NPC110958
0.6889	Remote Similarity	NPC19890
0.6667	Remote Similarity	NPC205915
0.6667	Remote Similarity	NPC80241
0.6667	Remote Similarity	NPC301641
0.6667	Remote Similarity	NPC485483
0.6429	Remote Similarity	NPC344161
0.64	Remote Similarity	NPC176586
0.64	Remote Similarity	NPC210354
0.6364	Remote Similarity	NPC476748
0.6279	Remote Similarity	NPC600801
0.6275	Remote Similarity	NPC191158
0.6275	Remote Similarity	NPC177644
0.619	Remote Similarity	NPC40352
0.619	Remote Similarity	NPC213711
0.5918	Remote Similarity	NPC158737
0.5918	Remote Similarity	NPC143895
0.5893	Remote Similarity	NPC282291
0.5893	Remote Similarity	NPC166137
0.5849	Remote Similarity	NPC3982
0.5833	Remote Similarity	NPC192255
0.5818	Remote Similarity	NPC145569
0.575	Remote Similarity	NPC31279
0.5745	Remote Similarity	NPC196937
0.56	Remote Similarity	NPC274356
0.56	Remote Similarity	NPC101748
0.5581	Remote Similarity	NPC604144
0.5417	Remote Similarity	NPC249788
0.5417	Remote Similarity	NPC485482
0.5417	Remote Similarity	NPC606623
0.54	Remote Similarity	NPC171550
0.54	Remote Similarity	NPC134764
0.5208	Remote Similarity	NPC223807
0.52	Remote Similarity	NPC104077
0.52	Remote Similarity	NPC219671
0.52	Remote Similarity	NPC147616
0.52	Remote Similarity	NPC485480
0.5192	Remote Similarity	NPC165128
0.5185	Remote Similarity	NPC18576
0.5172	Remote Similarity	NPC487679
0.5172	Remote Similarity	NPC56184
0.5172	Remote Similarity	NPC487678
0.5098	Remote Similarity	NPC92693
0.5091	Remote Similarity	NPC185908
0.5091	Remote Similarity	NPC230968
0.5091	Remote Similarity	NPC102260
0.5091	Remote Similarity	NPC482891
0.5088	Remote Similarity	NPC474158

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC528891 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4198
0.1-0.2	4706
0.2-0.3	225
0.3-0.4	18
0.4-0.5	2
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
0.5111	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