NPASS Compound

Natural Product: NPC566528

Natural Product ID	NPC566528
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	13-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-yl-trideca-2,4,12-trien-1-one
IUPAC Name	13-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-yl-trideca-2,4,12-trien-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 59 61 0 0 0 0 0 0 0 0999 V2000 -4.2574 -1.8978 -0.6785 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.2988 -1.2581 -0.3896 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1843 0.0659 0.1814 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9681 0.6005 0.3984 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.8890 1.9162 0.9662 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8131 2.5719 1.2378 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4556 1.9428 0.9516 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7848 1.8940 2.2911 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5316 1.2920 2.4072 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7166 1.8652 1.7492 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7391 1.9867 0.2776 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1131 2.5120 -0.2054 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2145 1.6210 0.1725 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9594 1.0680 -0.7400 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0909 0.1572 -0.4587 C 0 0 0 0 0 0 0 0 0 0 0 0 6.4432 -0.1768 0.8297 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5164 -1.0385 1.0307 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2337 -1.5647 -0.0226 C 0 0 0 0 0 0 0 0 0 0 0 0 9.3191 -2.4235 -0.1224 O 0 0 0 0 0 0 0 0 0 0 0 0 9.8455 -2.3146 -1.4254 C 0 0 0 0 0 0 0 0 0 0 0 0 8.7545 -1.8875 -2.2071 O 0 0 0 0 0 0 0 0 0 0 0 0 7.8841 -1.2327 -1.3150 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8234 -0.3812 -1.5104 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5786 -1.8142 -0.6149 N 0 0 0 0 0 0 0 0 0 0 0 0 -7.8347 -1.1620 -0.3177 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.9026 -2.1855 -0.6075 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.1410 -3.4882 -0.4711 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8291 -3.1304 -1.1816 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.0676 0.6263 0.4340 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1522 -0.0401 0.1106 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8412 2.4305 1.1989 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8117 3.5744 1.6709 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0133 2.6050 0.2072 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5620 0.9019 0.6029 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7517 2.9305 2.7517 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4827 1.3232 2.9748 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4588 0.1776 2.1334 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7945 1.1825 3.5308 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9522 2.8917 2.2148 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6067 1.2652 2.1293 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0532 2.8479 0.0044 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5233 1.0777 -0.2914 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3033 3.5144 0.2467 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0874 2.6519 -1.3042 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3903 1.4412 1.2153 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7571 1.2731 -1.7840 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9006 0.2192 1.6781 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7782 -1.2898 2.0644 H 0 0 0 0 0 0 0 0 0 0 0 0 10.1918 -3.2850 -1.8333 H 0 0 0 0 0 0 0 0 0 0 0 0 10.6171 -1.5246 -1.4608 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5250 -0.1013 -2.5308 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9767 -0.2230 -0.8801 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9022 -0.9042 0.7582 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2099 -2.0806 -1.6555 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.7508 -2.1275 0.1030 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9207 -3.6699 0.5984 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.6498 -4.3221 -0.9709 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0360 -3.8520 -0.9769 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0591 -3.0518 -2.2658 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 2 3 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 2 3 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 2 0 2 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 23 15 1 0 28 24 1 0 22 18 1 0 3 29 1 0 4 30 1 0 5 31 1 0 6 32 1 0 7 33 1 0 7 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 10 40 1 0 11 41 1 0 11 42 1 0 12 43 1 0 12 44 1 0 13 45 1 0 14 46 1 0 16 47 1 0 17 48 1 0 20 49 1 0 20 50 1 0 23 51 1 0 25 52 1 0 25 53 1 0 26 54 1 0 26 55 1 0 27 56 1 0 27 57 1 0 28 58 1 0 28 59 1 0 M END

Standard InCHIKey	CLVADUMCAXEPEK-UHFFFAOYSA-N
Standard InCHI	InChI=1S/C24H31NO3/c26-24(25-17-11-12-18-25)14-10-8-6-4-2-1-3-5-7-9-13-21-15-16-22-23(19-21)28-20-27-22/h6,8-10,13-16,19H,1-5,7,11-12,17-18,20H2
SMILES	O=C(C=CC=CCCCCCCC=CC1=CC=C2OCOC2=C1)N1CCCC1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	381.23	Volume:	416.903 ? Van der Waals volume.
Dense:	0.914	LogP:	5.243 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.67 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.176 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	19.0
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:	0.305	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.632	Fsp³:	0.458
MCE-18:	32.0 ? 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:	0.971	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.602 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.934 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.069	Promiscuous compounds:	0.057

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.719	MDCK Permeability:	-4.635
Pgp-inhibitor:	0.576	Pgp-substrate:	0.008
PAMPA:	0.007 ? 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):	0.004
20% Bioavailability (F20%):	0.117	30% Bioavailability (F30%):	0.011
50% Bioavailability (F50%):	0.515

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.875	MRP1:	0.398
Plasma Protein Binding (PPB):	98.1%	Volume Distribution (VD):	0.404
Fu:	1.746% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.858
OATP1B3 inhibitor:	0.993	BCRP inhibitor:	0.103
BSEP inhibitor:	0.999

ADMET: Metabolism

CYP1A2-inhibitor:	0.417	CYP1A2-substrate:	0.961
CYP2C19-inhibitor:	0.06	CYP2C19-substrate:	0.488
CYP2C9-inhibitor:	0.943	CYP2C9-substrate:	0.986
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.996
CYP3A4-inhibitor:	0.005	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.03	CYP2C8-inhibitor:	1.0
HLM stability:	0.2 ? 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):

4.11

Half-life (T1/2):

0.469

ADMET: Toxicity

hERG Blockers:	0.641	hERG Blockers (10um):	0.696
Human Hepatotoxicity (H-HT):	0.529	Drug-induced Liver Injury (DILI):	0.044
AMES Toxicity:	0.688	Rat Oral Acute Toxicity:	0.193
Maximum Recommended Daily Dose:	0.551	Skin Sensitization:	0.999
Carcinogencity:	0.282	Eye Corrosion:	0.123
Eye Irritation:	0.814	Respiratory Toxicity:	0.524
Drug-induced Neurotoxicity:	0.353	Ototoxicity:	0.338
Hematotoxicity:	0.115	Drug-induced Nephrotoxicity:	0.562
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.135
A549 Cytotoxicity:	0.663	Hek293 Cytotoxicity:	0.725
BCF:	1.707 ? 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:	4.948 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	6.403 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.654 ? 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
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1016/S0040-4039(01)00209-X]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10575373]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	leaf	n.a.	PMID[15467205]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	whole plant	n.a.	PMID[16808005]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23102654]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31096694]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31103896]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[31766491]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38067483]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38474459]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	Fruit	n.a.	n.a.	Database[FooDB]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28928	Piper nigrum	Species	Piperaceae	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 NPC566528 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	22133
0.1-0.2	26307
0.2-0.3	1261
0.3-0.4	92
0.4-0.5	23
0.5-0.6	15
0.6-0.7	6
0.7-0.8	1
0.8-0.85	0
0.85-0.9	6
0.9-0.95	2
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC220923
1.0	High Similarity	NPC196609
0.9808	High Similarity	NPC328419
0.9074	High Similarity	NPC73883
0.9074	High Similarity	NPC251454
0.8889	High Similarity	NPC103947
0.8889	High Similarity	NPC45783
0.8704	High Similarity	NPC230698
0.8704	High Similarity	NPC99078
0.8704	High Similarity	NPC96406
0.8519	High Similarity	NPC193673
0.7679	Intermediate Similarity	NPC159150
0.7368	Intermediate Similarity	NPC205178
0.7368	Intermediate Similarity	NPC227218
0.7321	Intermediate Similarity	NPC255817
0.7321	Intermediate Similarity	NPC136330
0.7143	Intermediate Similarity	NPC94280
0.7119	Intermediate Similarity	NPC318862
0.7069	Intermediate Similarity	NPC194359
0.7069	Intermediate Similarity	NPC28641
0.7069	Intermediate Similarity	NPC180647
0.7069	Intermediate Similarity	NPC225745
0.6909	Remote Similarity	NPC167096
0.6909	Remote Similarity	NPC605721
0.6774	Remote Similarity	NPC95366
0.6727	Remote Similarity	NPC217574
0.6119	Remote Similarity	NPC41331
0.6119	Remote Similarity	NPC291449
0.597	Remote Similarity	NPC71105
0.5968	Remote Similarity	NPC145446
0.5968	Remote Similarity	NPC137172
0.5932	Remote Similarity	NPC470707
0.5672	Remote Similarity	NPC156944
0.5556	Remote Similarity	NPC69670
0.5522	Remote Similarity	NPC152186
0.5469	Remote Similarity	NPC248505
0.5397	Remote Similarity	NPC252107
0.5373	Remote Similarity	NPC114845
0.5362	Remote Similarity	NPC170583
0.5362	Remote Similarity	NPC270811
0.5362	Remote Similarity	NPC471073
0.5294	Remote Similarity	NPC191302
0.5079	Remote Similarity	NPC469808

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC566528 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4521
0.1-0.2	4538
0.2-0.3	85
0.3-0.4	4
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7321	Intermediate 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