NPASS Compound

Natural Product: NPC205178

Natural Product ID	NPC205178
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-(Benzo[D][1,3]Dioxol-5-Yl)-1-(Piperidin-1-Yl)Hepta-2,4,6-Trien-1-One
IUPAC Name	(2E,4E,6E)-7-(1,3-benzodioxol-5-yl)-1-piperidin-1-ylhepta-2,4,6-trien-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL324315
PubChem CID	10244953
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000002] Organoheterocyclic compounds [CHEMONTID:0000296] Benzodioxoles

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 44 46 0 0 0 0 0 0 0 0999 V2000 0.7235 -0.2302 0.2607 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.1433 -0.6740 1.1531 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5692 -0.7245 0.7391 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5013 -1.1528 1.5632 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9162 -1.2726 1.3387 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.5560 -1.7072 2.3968 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7265 -1.0257 0.2538 N 0 0 0 0 0 0 0 0 0 0 0 0 -6.2120 -1.1889 0.4288 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.8298 0.0048 -0.2763 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8852 1.1823 -0.3757 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6183 0.8714 -1.1467 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4127 -0.6318 -1.0977 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1549 -0.1471 0.5865 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0116 0.2952 -0.3055 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4265 0.3930 -0.0270 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0222 0.0490 1.1570 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3872 0.1702 1.3517 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2230 0.6441 0.3638 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6417 0.9956 -0.8354 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2843 0.8738 -1.0254 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6959 1.4366 -1.6471 O 0 0 0 0 0 0 0 0 0 0 0 0 8.8792 0.8547 -1.1143 C 0 0 0 0 0 0 0 0 0 0 0 0 8.5902 0.8693 0.2713 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4295 0.0847 -0.7255 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1675 -0.9823 2.1277 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8664 -0.3974 -0.2336 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0674 -1.4503 2.5603 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5476 -2.0906 -0.1102 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4463 -1.2754 1.4809 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2684 -0.2731 -1.2557 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6715 0.3399 0.3637 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4194 1.9621 -0.9499 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6941 1.5438 0.6445 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6505 1.1904 -2.1905 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.7772 1.3892 -0.6410 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2426 -1.0207 -1.7940 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5029 -0.9943 -1.5329 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4841 -0.4580 1.5755 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6249 0.5943 -1.2843 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4256 -0.3275 1.9680 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8081 -0.1159 2.3075 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8405 1.1486 -1.9588 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9329 -0.1824 -1.4962 H 0 0 0 0 0 0 0 0 0 0 0 0 9.7714 1.4298 -1.3686 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 5 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 1 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 19 21 1 0 21 22 1 0 22 23 1 0 12 7 1 0 20 15 1 0 23 18 1 0 1 24 1 0 2 25 1 0 3 26 1 0 4 27 1 0 8 28 1 0 8 29 1 0 9 30 1 0 9 31 1 0 10 32 1 0 10 33 1 0 11 34 1 0 11 35 1 0 12 36 1 0 12 37 1 0 13 38 1 0 14 39 1 0 16 40 1 0 17 41 1 0 20 42 1 0 22 43 1 0 22 44 1 0 M END

Standard InCHIKey	DLKOUKNODPCIHZ-UMYWTXKFSA-N
Standard InCHI	InChI=1S/C19H21NO3/c21-19(20-12-6-3-7-13-20)9-5-2-1-4-8-16-10-11-17-18(14-16)23-15-22-17/h1-2,4-5,8-11,14H,3,6-7,12-13,15H2/b2-1+,8-4+,9-5+
SMILES	C(=CC=CC(=O)N1CCCCC1)/C=C/c1ccc2c(c1)OCO2

Calculated Properties

Physi-Chem Properties

Molecular Weight:	311.15	Volume:	330.423 ? Van der Waals volume.
Dense:	0.942	LogP:	2.579 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	2.648 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.937 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	20.0
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:	0.63	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.53	Fsp³:	0.316
MCE-18:	34.72 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.696	Fluc inhibitor:	1.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.688 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.845 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.051	Promiscuous compounds:	0.05

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.757	MDCK Permeability:	-4.678
Pgp-inhibitor:	0.941	Pgp-substrate:	0.018
PAMPA:	0.087 ? 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):	0.001
20% Bioavailability (F20%):	0.071	30% Bioavailability (F30%):	0.004
50% Bioavailability (F50%):	0.465

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.053	MRP1:	0.006
Plasma Protein Binding (PPB):	97.849%	Volume Distribution (VD):	-0.22
Fu:	2.314% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.976
OATP1B3 inhibitor:	0.945	BCRP inhibitor:	0.006
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.827	CYP1A2-substrate:	0.963
CYP2C19-inhibitor:	0.466	CYP2C19-substrate:	0.624
CYP2C9-inhibitor:	0.073	CYP2C9-substrate:	0.995
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	0.998
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	1.0
CYP2B6-substrate:	0.008	CYP2C8-inhibitor:	0.991
HLM stability:	0.949 ? 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):

5.686

Half-life (T1/2):

0.443

ADMET: Toxicity

hERG Blockers:	0.336	hERG Blockers (10um):	0.457
Human Hepatotoxicity (H-HT):	0.624	Drug-induced Liver Injury (DILI):	0.691
AMES Toxicity:	0.807	Rat Oral Acute Toxicity:	0.361
Maximum Recommended Daily Dose:	0.793	Skin Sensitization:	0.682
Carcinogencity:	0.782	Eye Corrosion:	0.005
Eye Irritation:	0.604	Respiratory Toxicity:	0.83
Drug-induced Neurotoxicity:	0.717	Ototoxicity:	0.369
Hematotoxicity:	0.424	Drug-induced Nephrotoxicity:	0.52
Genotoxicity:	0.776	RPMI-8226 Immunitoxicity:	0.113
A549 Cytotoxicity:	0.107	Hek293 Cytotoxicity:	0.54
BCF:	1.172 ? 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:	3.728 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.328 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.687 ? 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]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[16872768]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	fruits	n.a.	n.a.	PMID[20839888]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23102654]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23434420]
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]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
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]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
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]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO26237	Piper longum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO26237	Piper longum	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[TM-MC]
NPO28928	Piper nigrum	Species	Piperaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26237	Piper longum	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
NPO28928	Piper nigrum	Raw	Fruit	525	230	820	mg/100g	Database [DUKE]

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

Activity Type	# Activity
Inhibition	1
IC50	3

Activity Type	# Activity
Individual protein	1
Organism	3

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT570	Individual protein	Arachidonate 5-lipoxygenase	Homo sapiens	Inhibition	=	76.02	%	PMID[30638966]

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	10670.0	nM	PMID[15177472]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	7400.0	nM	PMID[15177472]
NPT580	Organism	Trypanosoma cruzi	Trypanosoma cruzi	IC50	=	7000.0	nM	PMID[20185316]

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 NPC205178 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	21503
0.1-0.2	26700
0.2-0.3	1422
0.3-0.4	167
0.4-0.5	31
0.5-0.6	14
0.6-0.7	5
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	2
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC227218
0.9167	High Similarity	NPC255817
0.9167	High Similarity	NPC136330
0.8958	High Similarity	NPC94280
0.7818	Intermediate Similarity	NPC73883
0.7818	Intermediate Similarity	NPC251454
0.7636	Intermediate Similarity	NPC103947
0.7636	Intermediate Similarity	NPC45783
0.7368	Intermediate Similarity	NPC220923
0.7368	Intermediate Similarity	NPC196609
0.7255	Intermediate Similarity	NPC167096
0.7255	Intermediate Similarity	NPC605721
0.7193	Intermediate Similarity	NPC328419
0.7091	Intermediate Similarity	NPC159150
0.7059	Intermediate Similarity	NPC217574
0.6842	Remote Similarity	NPC230698
0.6842	Remote Similarity	NPC99078
0.6842	Remote Similarity	NPC96406
0.6667	Remote Similarity	NPC193673
0.6182	Remote Similarity	NPC470707
0.5932	Remote Similarity	NPC194359
0.5932	Remote Similarity	NPC28641
0.5932	Remote Similarity	NPC145446
0.5932	Remote Similarity	NPC180647
0.5932	Remote Similarity	NPC137172
0.5932	Remote Similarity	NPC225745
0.5714	Remote Similarity	NPC95366
0.5636	Remote Similarity	NPC199209
0.5593	Remote Similarity	NPC252107
0.5484	Remote Similarity	NPC318862
0.5254	Remote Similarity	NPC469808
0.52	Remote Similarity	NPC127326
0.5161	Remote Similarity	NPC248505
0.5156	Remote Similarity	NPC251466

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC205178 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4117
0.1-0.2	4911
0.2-0.3	113
0.3-0.4	7
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	1
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.9167	High 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