NPASS Compound

Natural Product: NPC571604

Natural Product ID	NPC571604
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-yl-hept-2-en-1-one
IUPAC Name	7-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-yl-hept-2-en-1-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 45 47 0 0 0 0 0 0 0 0999 V2000 -4.2229 2.3009 -0.4502 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1426 1.0442 -0.2978 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8703 0.3484 -0.4965 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8116 1.0459 -0.8355 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5192 0.3575 -1.0398 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4557 0.9683 -0.0309 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7910 0.2657 -0.2331 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8027 0.8483 0.7610 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0960 0.1521 0.5487 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4417 -0.9972 1.2195 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6462 -1.6266 1.0074 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5408 -1.0813 0.0848 C 0 0 0 0 0 0 0 0 0 0 0 0 7.8109 -1.4498 -0.3615 O 0 0 0 0 0 0 0 0 0 0 0 0 8.4204 -0.2925 -0.9190 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2909 0.3735 -1.4430 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2293 0.0689 -0.6064 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9969 0.6684 -0.3557 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.2692 0.2722 0.0669 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.2783 -1.1565 0.2633 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5623 -1.3831 1.0697 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4899 -0.3858 0.3957 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5861 0.8320 0.2944 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.7809 -0.7147 -0.3725 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8194 2.1202 -0.9798 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1531 0.5183 -2.0788 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6447 -0.7150 -0.8069 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1334 0.7934 0.9989 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6145 2.0379 -0.2279 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6084 -0.8038 -0.0157 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1561 0.3488 -1.2727 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4118 0.6161 1.7803 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8591 1.9330 0.6715 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7551 -1.4225 1.9327 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9400 -2.5335 1.5247 H 0 0 0 0 0 0 0 0 0 0 0 0 8.8497 0.3177 -0.1093 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1572 -0.5645 -1.7079 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7776 1.5794 -0.9187 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4569 -1.5371 0.8689 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3165 -1.7181 -0.6914 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.9086 -2.4118 0.9964 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3680 -1.0263 2.0858 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7168 -0.7148 -0.6369 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.3913 -0.1886 1.0022 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6128 1.4419 1.2207 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8636 1.4707 -0.5683 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 3 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 2 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 17 9 1 0 22 18 1 0 16 12 1 0 3 23 1 0 4 24 1 0 5 25 1 0 5 26 1 0 6 27 1 0 6 28 1 0 7 29 1 0 7 30 1 0 8 31 1 0 8 32 1 0 10 33 1 0 11 34 1 0 14 35 1 0 14 36 1 0 17 37 1 0 19 38 1 0 19 39 1 0 20 40 1 0 20 41 1 0 21 42 1 0 21 43 1 0 22 44 1 0 22 45 1 0 M END

Standard InCHIKey	AXDKDWWPOMVARR-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C18H23NO3/c20-18(19-11-5-6-12-19)8-4-2-1-3-7-15-9-10-16-17(13-15)22-14-21-16/h4,8-10,13H,1-3,5-7,11-12,14H2
SMILES	O=C(C=CCCCCC1=CC=C2OCOC2=C1)N1CCCC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	301.17	Volume:	318.4 ? Van der Waals volume.
Dense:	0.946	LogP:	3.562 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.086 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.059 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	17.0
TPSA:	38.77 ? Topological Polar Surface Area.	H-Bond Acceptor:	4.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	4.0

MedChem Properties

QED Drug-Likeness Score:	0.598	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.221	Fsp³:	0.5
MCE-18:	33.185 ? 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:	0.11	Fluc inhibitor:	0.6 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.254 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.662 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.014	Promiscuous compounds:	0.037

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.578	MDCK Permeability:	-4.669
Pgp-inhibitor:	0.944	Pgp-substrate:	0.025
PAMPA:	0.018 ? 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):	0.012
20% Bioavailability (F20%):	0.076	30% Bioavailability (F30%):	0.008
50% Bioavailability (F50%):	0.368

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.958	MRP1:	0.494
Plasma Protein Binding (PPB):	98.744%	Volume Distribution (VD):	0.366
Fu:	1.173% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.806
OATP1B3 inhibitor:	0.266	BCRP inhibitor:	0.066
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.98	CYP1A2-substrate:	0.95
CYP2C19-inhibitor:	0.99	CYP2C19-substrate:	0.982
CYP2C9-inhibitor:	1.0	CYP2C9-substrate:	1.0
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.111	CYP3A4-substrate:	0.999
CYP2B6-substrate:	0.336	CYP2C8-inhibitor:	0.995
HLM stability:	0.52 ? 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):

4.483

Half-life (T1/2):

0.36

ADMET: Toxicity

hERG Blockers:	0.521	hERG Blockers (10um):	0.639
Human Hepatotoxicity (H-HT):	0.581	Drug-induced Liver Injury (DILI):	0.218
AMES Toxicity:	0.485	Rat Oral Acute Toxicity:	0.285
Maximum Recommended Daily Dose:	0.494	Skin Sensitization:	0.898
Carcinogencity:	0.348	Eye Corrosion:	0.205
Eye Irritation:	0.884	Respiratory Toxicity:	0.692
Drug-induced Neurotoxicity:	0.519	Ototoxicity:	0.312
Hematotoxicity:	0.312	Drug-induced Nephrotoxicity:	0.603
Genotoxicity:	0.022	RPMI-8226 Immunitoxicity:	0.101
A549 Cytotoxicity:	0.295	Hek293 Cytotoxicity:	0.546
BCF:	1.598 ? 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:	4.265 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.613 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.042 ? 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
NPO30128	Piper boehmeriaefolium	Species	Piperaceae	Eukaryota	whole plant	Luxi County, Yunnan Province, China	2008-OCT	PMID[21158422]
NPO30128	Piper boehmeriaefolium	Species	Piperaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[21158422]
NPO30128	Piper boehmeriaefolium	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30128	Piper boehmeriaefolium	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]

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 NPC571604 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	20462
0.1-0.2	27598
0.2-0.3	1540
0.3-0.4	191
0.4-0.5	37
0.5-0.6	19
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC248505
0.8	Intermediate Similarity	NPC95366
0.7692	Intermediate Similarity	NPC252107
0.7091	Intermediate Similarity	NPC145446
0.7091	Intermediate Similarity	NPC137172
0.6792	Remote Similarity	NPC608515
0.6667	Remote Similarity	NPC605639
0.6379	Remote Similarity	NPC193673
0.6271	Remote Similarity	NPC230698
0.6271	Remote Similarity	NPC99078
0.6271	Remote Similarity	NPC96406
0.6207	Remote Similarity	NPC159150
0.5781	Remote Similarity	NPC270811
0.5781	Remote Similarity	NPC471073
0.5714	Remote Similarity	NPC246974
0.5556	Remote Similarity	NPC328419
0.5469	Remote Similarity	NPC220923
0.5469	Remote Similarity	NPC196609
0.5455	Remote Similarity	NPC147247
0.5424	Remote Similarity	NPC94280
0.5397	Remote Similarity	NPC103947
0.5397	Remote Similarity	NPC45783
0.5333	Remote Similarity	NPC255817
0.5333	Remote Similarity	NPC136330
0.5312	Remote Similarity	NPC73883
0.5312	Remote Similarity	NPC251454
0.5263	Remote Similarity	NPC217574
0.5172	Remote Similarity	NPC167096
0.5172	Remote Similarity	NPC605721
0.5161	Remote Similarity	NPC205178
0.5161	Remote Similarity	NPC227218

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC571604 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3897
0.1-0.2	5069
0.2-0.3	173
0.3-0.4	9
0.4-0.5	1
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
0.5333	Remote Similarity	NPD2492	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