NPASS Compound

Natural Product: NPC318862

Natural Product ID	NPC318862
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	1-[(4E,9E)-10-(3,4-Methylenedioxyphenyl)-4,9-Nonadienoyl]Pyrrolidine
IUPAC Name	(4E,10E)-11-(1,3-benzodioxol-5-yl)-1-pyrrolidin-1-ylundeca-4,10-dien-1-one
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL1669574
PubChem CID	50994146
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 55 57 0 0 0 0 0 0 0 0999 V2000 -7.1880 1.8701 1.1536 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.2015 0.4316 1.6871 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.4484 -0.2677 0.5477 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.3282 0.6169 0.3736 N 0 0 0 0 0 0 0 0 0 0 0 0 -5.8434 1.9634 0.4393 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9854 0.2265 0.1767 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0578 1.0987 0.0318 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6653 -1.2218 0.1403 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1865 -1.3732 -0.0900 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7459 -0.7645 -1.3605 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8500 0.2002 -1.3542 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3554 0.8643 -2.5948 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1474 0.6492 -2.6831 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3940 -0.8565 -2.7330 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8750 -1.1538 -2.8230 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5950 -0.5975 -1.6299 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2446 -1.4127 -0.8596 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9684 -0.9804 0.3102 C 0 0 0 0 0 0 0 0 0 0 0 0 5.0332 0.3349 0.7113 C 0 0 0 0 0 0 0 0 0 0 0 0 5.7341 0.7551 1.8444 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3957 -0.1753 2.6059 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3459 -1.4979 2.2253 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6507 -1.8912 1.1068 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0037 0.4962 3.6600 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9655 1.8894 3.4192 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9413 1.9917 2.4375 O 0 0 0 0 0 0 0 0 0 0 0 0 -7.2992 2.6089 1.9494 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9785 1.9075 0.3752 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2083 0.0443 1.8233 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5404 0.3451 2.5700 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1430 -1.2888 0.8543 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0912 -0.3220 -0.3493 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9297 2.4426 -0.5501 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1677 2.6295 1.0494 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2397 -1.7030 -0.6928 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0087 -1.6917 1.0695 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9556 -2.4617 -0.0878 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.5934 -0.9368 0.7347 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1251 -1.0704 -2.3352 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4018 0.5827 -0.4197 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8529 0.4806 -3.4988 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5105 1.9715 -2.4947 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5928 1.0155 -1.7277 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5769 1.1391 -3.5703 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9530 -1.3212 -1.8329 H 0 0 0 0 0 0 0 0 0 0 0 0 0.8813 -1.2762 -3.6134 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0016 -2.2401 -2.8869 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2662 -0.6639 -3.7285 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5401 0.4723 -1.4627 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2578 -2.4836 -1.0890 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5294 1.1239 0.1501 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8785 -2.2082 2.8473 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6140 -2.9501 0.8069 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9206 2.2893 3.0793 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5942 2.3696 4.3542 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 4 6 1 0 6 7 2 0 6 8 1 0 8 9 1 0 9 10 1 0 10 11 2 3 11 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 2 3 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 21 24 1 0 24 25 1 0 25 26 1 0 5 1 1 0 23 18 1 0 26 20 1 0 1 27 1 0 1 28 1 0 2 29 1 0 2 30 1 0 3 31 1 0 3 32 1 0 5 33 1 0 5 34 1 0 8 35 1 0 8 36 1 0 9 37 1 0 9 38 1 0 10 39 1 0 11 40 1 0 12 41 1 0 12 42 1 0 13 43 1 0 13 44 1 0 14 45 1 0 14 46 1 0 15 47 1 0 15 48 1 0 16 49 1 0 17 50 1 0 19 51 1 0 22 52 1 0 23 53 1 0 25 54 1 0 25 55 1 0 M END

Standard InCHIKey	LALIMVNVUDRVIW-RQBRCHNQSA-N
Standard InCHI	InChI=1S/C22H29NO3/c24-22(23-15-9-10-16-23)12-8-6-4-2-1-3-5-7-11-19-13-14-20-21(17-19)26-18-25-20/h4,6-7,11,13-14,17H,1-3,5,8-10,12,15-16,18H2/b6-4+,11-7+
SMILES	C1CCN(C1)C(=O)CCC=CCCCCC=CC2=CC3=C(C=C2)OCO3

Calculated Properties

Physi-Chem Properties

Molecular Weight:	355.21	Volume:	384.947 ? Van der Waals volume.
Dense:	0.923	LogP:	5.125 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.595 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-5.076 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	10.0	Rigid Bonds:	18.0
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:	0.465	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	2.478	Fsp³:	0.5
MCE-18:	32.242 ? 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:	0.176	Fluc inhibitor:	0.911 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.168 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.675 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.014	Promiscuous compounds:	0.045

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.774	MDCK Permeability:	-4.699
Pgp-inhibitor:	0.631	Pgp-substrate:	0.012
PAMPA:	0.004 ? 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%):	0.029	30% Bioavailability (F30%):	0.002
50% Bioavailability (F50%):	0.507

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.851	MRP1:	0.683
Plasma Protein Binding (PPB):	89.897%	Volume Distribution (VD):	-0.071
Fu:	9.496% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.253
OATP1B3 inhibitor:	0.642	BCRP inhibitor:	0.04
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.003	CYP1A2-substrate:	0.166
CYP2C19-inhibitor:	0.997	CYP2C19-substrate:	0.342
CYP2C9-inhibitor:	0.998	CYP2C9-substrate:	0.294
CYP2D6-inhibitor:	1.0	CYP2D6-substrate:	1.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.959
CYP2B6-substrate:	0.163	CYP2C8-inhibitor:	0.992
HLM stability:	0.955 ? 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):

4.592

Half-life (T1/2):

0.315

ADMET: Toxicity

hERG Blockers:	0.563	hERG Blockers (10um):	0.657
Human Hepatotoxicity (H-HT):	0.474	Drug-induced Liver Injury (DILI):	0.007
AMES Toxicity:	0.511	Rat Oral Acute Toxicity:	0.158
Maximum Recommended Daily Dose:	0.402	Skin Sensitization:	0.999
Carcinogencity:	0.202	Eye Corrosion:	0.309
Eye Irritation:	0.815	Respiratory Toxicity:	0.342
Drug-induced Neurotoxicity:	0.247	Ototoxicity:	0.251
Hematotoxicity:	0.065	Drug-induced Nephrotoxicity:	0.607
Genotoxicity:	0.001	RPMI-8226 Immunitoxicity:	0.09
A549 Cytotoxicity:	0.537	Hek293 Cytotoxicity:	0.581
BCF:	1.589 ? 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:	4.293 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.73 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.117 ? 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

Activity Type	# Activity
IC50	9

Activity Type	# Activity
Cell line	8
Non-molecular	1

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
NPT165	Cell line	HeLa	Homo sapiens	IC50	=	12.19	ug.mL-1	PMID[21158422]
NPT81	Cell line	A549	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT83	Cell line	MCF7	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT133	Cell line	ZR-75-1	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT134	Cell line	SK-BR-3	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT90	Cell line	DU-145	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT91	Cell line	KB	Homo sapiens	IC50	>	40000.0	nM	PMID[25241925]
NPT20529	Non-molecular	NON-PROTEIN TARGET	n.a.	IC50	>	40000.0	nM	PMID[25241925]

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 NPC318862 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	21527
0.1-0.2	26834
0.2-0.3	1348
0.3-0.4	92
0.4-0.5	22
0.5-0.6	15
0.6-0.7	8
0.7-0.8	0
0.8-0.85	4
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8462	Intermediate Similarity	NPC194359
0.8462	Intermediate Similarity	NPC28641
0.8462	Intermediate Similarity	NPC180647
0.8462	Intermediate Similarity	NPC225745
0.7636	Intermediate Similarity	NPC193673
0.75	Intermediate Similarity	NPC230698
0.75	Intermediate Similarity	NPC99078
0.75	Intermediate Similarity	NPC96406
0.7241	Intermediate Similarity	NPC328419
0.7119	Intermediate Similarity	NPC220923
0.7119	Intermediate Similarity	NPC196609
0.6842	Remote Similarity	NPC159150
0.65	Remote Similarity	NPC103947
0.65	Remote Similarity	NPC45783
0.6393	Remote Similarity	NPC73883
0.6393	Remote Similarity	NPC251454
0.6182	Remote Similarity	NPC217574
0.6071	Remote Similarity	NPC167096
0.6071	Remote Similarity	NPC605721
0.5781	Remote Similarity	NPC152186
0.5763	Remote Similarity	NPC94280
0.5692	Remote Similarity	NPC156944
0.5667	Remote Similarity	NPC255817
0.5667	Remote Similarity	NPC136330
0.5522	Remote Similarity	NPC71105
0.5484	Remote Similarity	NPC205178
0.5484	Remote Similarity	NPC227218
0.5441	Remote Similarity	NPC41331
0.5441	Remote Similarity	NPC291449
0.5303	Remote Similarity	NPC191302
0.5167	Remote Similarity	NPC470707
0.5167	Remote Similarity	NPC608515
0.5082	Remote Similarity	NPC605639
0.5079	Remote Similarity	NPC69670

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC318862 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4506
0.1-0.2	4525
0.2-0.3	114
0.3-0.4	3
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
0.5667	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